From c37cd21836b70e06a30e773ccbb317ce0f899f2e Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Apr 2024 14:53:25 -0700 Subject: [PATCH 001/161] make JSON file required in vcf2gvf.py --- bin/vcf2gvf.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/bin/vcf2gvf.py b/bin/vcf2gvf.py index 740d32c6..c98bcf7a 100755 --- a/bin/vcf2gvf.py +++ b/bin/vcf2gvf.py @@ -131,7 +131,7 @@ def parse_args(): help='Alternate frequency cutoff for ' 'clade-defining mutations') parser.add_argument('--gene_positions', type=str, - default=None, + default=None, required=True, help='gene positions in JSON format') parser.add_argument('--strain', type=str, default=None, From 9a4f86d418387895913dfe5ab2077b63587c650f Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Apr 2024 15:09:38 -0700 Subject: [PATCH 002/161] add new attribute, 'transcript_id', using locus_tag from JSON --- bin/functions.py | 4 +++- bin/vcf2gvf.py | 5 +++-- 2 files changed, 6 insertions(+), 3 deletions(-) diff --git a/bin/functions.py b/bin/functions.py index 43e51ab6..368fa0e6 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -4,7 +4,7 @@ # standard variables used by all scripts empty_attributes = 'ID=;Name=;alias=;gene=;protein_name=;protein_symbol=;\ - protein_id=;ps_filter=;ps_exc=; \ + protein_id=;transcript_id=;ps_filter=;ps_exc=; \ mat_pep=;mat_pep_desc=;mat_pep_acc=;ro=;ao=;dp=;sample_size=; \ Reference_seq=;Variant_seq=;nt_name=;aa_name=;hgvs_nt=;hgvs_aa=;hgvs_alias=; \ vcf_gene=;mutation_type=;viral_lineage=;multi_aa_name=; \ @@ -502,6 +502,7 @@ def map_pos_to_gene_protein(pos, GENE_PROTEIN_POSITIONS_DICT): protein_name = GENE_PROTEIN_POSITIONS_DICT[entry]["product"] protein_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_alias"] protein_id = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_id"] + transcript_id = GENE_PROTEIN_POSITIONS_DICT[entry]["locus_tag"] # fill in attributes for mutations in this CDS region cds_mask = df[pos_column].astype(int).between(start, end, inclusive="both") @@ -509,6 +510,7 @@ def map_pos_to_gene_protein(pos, GENE_PROTEIN_POSITIONS_DICT): df.loc[cds_mask, "protein_name"] = protein_name df.loc[cds_mask, "protein_symbol"] = protein_symbol df.loc[cds_mask, "protein_id"] = protein_id + df.loc[cds_mask, "transcript_id"] = transcript_id # label all mutations that didn't belong to any gene as "intergenic" df.loc[df["gene"].isna(), "gene"] = "intergenic" diff --git a/bin/vcf2gvf.py b/bin/vcf2gvf.py index c98bcf7a..b2a28729 100755 --- a/bin/vcf2gvf.py +++ b/bin/vcf2gvf.py @@ -11,7 +11,7 @@ ['ID', 'Name', 'gene', 'protein_name', 'protein_symbol', 'protein_id', 'ps_filter', 'ps_exc', 'mat_pep', 'mat_pep_desc','mat_pep_acc', 'ro', 'ao', 'dp', 'sample_size', 'Reference_seq', 'Variant_seq', 'nt_name', 'aa_name', 'hgvs_nt', 'hgvs_aa', 'hgvs_alias', 'vcf_gene', 'mutation_type', -'viral_lineage', 'alternate_frequency'] +'viral_lineage', 'alternate_frequency', 'transcript_id'] """ import argparse @@ -88,7 +88,8 @@ def vcftogvf(vcf, strain, GENE_PROTEIN_POSITIONS_DICT, sample_size): new_gvf["protein_name"] = json_df["protein_name"] new_gvf["protein_symbol"] = json_df["protein_symbol"] new_gvf["protein_id"] = json_df["protein_id"] - + new_gvf["transcript_id"] = json_df["transcript_id"] + # add 'alias' column for ORF1a/b mutations new_gvf = add_alias_names(new_gvf, GENE_PROTEIN_POSITIONS_DICT) From 407381cee3232e7b70b84e2646b2a189e32299cc Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Apr 2024 15:37:06 -0700 Subject: [PATCH 003/161] add transcript_id in parentheses for HGVS nt names --- bin/functions.py | 11 +++++++---- 1 file changed, 7 insertions(+), 4 deletions(-) diff --git a/bin/functions.py b/bin/functions.py index 368fa0e6..c66fae9b 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -89,18 +89,21 @@ def add_hgvs_names(new_gvf): #df.loc[mask, 'val'] = df.loc[mask, 'val'].apply(f) # add hgvs nt snp names nt_snp_mask = new_gvf['nt_name'].str.contains(nt_snp_regex, regex=True) - new_gvf.loc[nt_snp_mask, 'hgvs_nt'] = new_gvf['#seqid'] + ":" + \ + new_gvf.loc[nt_snp_mask, 'hgvs_nt'] = new_gvf['#seqid'] + "(" + new_gvf['transcript_id'] + "):" + \ new_gvf.loc[nt_snp_mask, 'nt_name'].apply(rewrite_nt_snps_as_hgvs) # add hgvs nt dels and dups nt_del_dup_mask = new_gvf['nt_name'].str.contains(nt_del_dup_regex, regex=True) - new_gvf.loc[nt_del_dup_mask,'hgvs_nt'] = new_gvf['#seqid'] + ":" + \ + new_gvf.loc[nt_del_dup_mask,'hgvs_nt'] = new_gvf['#seqid'] + "(" + new_gvf['transcript_id'] + "):" + \ new_gvf.loc[nt_del_dup_mask, 'nt_name'].apply(remove_nts_from_nt_name) # add hgvs nt ins nt_ins_mask = new_gvf['nt_name'].str.contains(nt_ins_regex, regex=True) - new_gvf.loc[nt_ins_mask, 'hgvs_nt'] = new_gvf['#seqid'] + ":" + new_gvf['nt_name'] + new_gvf.loc[nt_ins_mask, 'hgvs_nt'] = new_gvf['#seqid'] + "(" + new_gvf['transcript_id'] + "):" + new_gvf['nt_name'] # add hgvs nt delins: change to eg. g.123_129delinsAC nt_delins_mask = new_gvf['nt_name'].str.contains(nt_delins_regex, regex=True) - #new_gvf.loc[nt_delins_mask, 'hgvs_nt'] = new_gvf['#seqid'] + ":" + "TBA!" #new_gvf['nt_name'] + #new_gvf.loc[nt_delins_mask, 'hgvs_nt'] = new_gvf['#seqid'] + "(" + new_gvf['transcript_id'] + "):" + "TBA!" #new_gvf['nt_name'] + + # remove transcript id in parentheses for all HGVS nucleotide names where 'transcript_id'=='n/a' + new_gvf['hgvs_nt'] = new_gvf['hgvs_nt'].str.replace("(n/a)", "", regex=False) # define aa regex patterns aa_snp_regex = "[A-Z*][0-9\\-]+[A-Z*]" From ecd19c4ae84f327b12d0bb824fc876f049a8304b Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Apr 2024 16:39:55 -0700 Subject: [PATCH 004/161] get rid of UserWarning for match groups --- bin/functions.py | 4 ++-- 1 file changed, 2 insertions(+), 2 deletions(-) diff --git a/bin/functions.py b/bin/functions.py index c66fae9b..1479eca5 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -80,7 +80,7 @@ def add_hgvs_names(new_gvf): # for SNPs, eg. g.C45T, g.C-45T nt_snp_regex = "[a-z]\\.[A-Z][0-9\\-]+[A-Z]" # for dels and dups, eg. g.254_259delTGGTTG, g.361delA - nt_del_dup_regex = "[a-z]\\.[0-9\\-_]+(del|dup)[A-Z]+" + nt_del_dup_regex = "[a-z]\\.[0-9\\-_]+(?:del|dup)[A-Z]+" # for ins nt_ins_regex = "[a-z]\\.[0-9\\-_]+ins[A-Z]+" # for delins, eg. g.GCC10182_10184ACA @@ -107,7 +107,7 @@ def add_hgvs_names(new_gvf): # define aa regex patterns aa_snp_regex = "[A-Z*][0-9\\-]+[A-Z*]" - aa_other_regex = "[A-Z*]+[0-9\\-]+(del|delins|ins|dup|fs|ext)[A-Z*]*" + aa_other_regex = "[A-Z*]+[0-9\\-]+(?:del|delins|ins|dup|fs|ext)[A-Z*]*" # fill in 'hgvs_aa' # add hgvs aa snps to rows with protein_id!=n/a From 1a57d85673e0ec4237f22a6aa350fc04792687f5 Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Apr 2024 16:49:42 -0700 Subject: [PATCH 005/161] remove unused imports --- bin/vcf2gvf.py | 3 +-- 1 file changed, 1 insertion(+), 2 deletions(-) diff --git a/bin/vcf2gvf.py b/bin/vcf2gvf.py index b2a28729..0e77490c 100755 --- a/bin/vcf2gvf.py +++ b/bin/vcf2gvf.py @@ -19,9 +19,8 @@ import numpy as np import json from functions import parse_INFO, find_sample_size, \ - unnest_multi, get_unknown_labels, separate_attributes, rejoin_attributes, \ + get_unknown_labels, separate_attributes, rejoin_attributes, \ clade_defining_threshold, map_pos_to_gene_protein, add_alias_names, \ - convert_amino_acid_codes, rewrite_nt_snps_as_hgvs, remove_nts_from_nt_name, \ add_hgvs_names from functions import empty_attributes, gvf_columns, vcf_columns, pragmas From 047f08521079dab64583312f43ca04321cb2b49c Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Apr 2024 16:56:46 -0700 Subject: [PATCH 006/161] include alias_protein_id in HGVS alias names, and make a new attribute called 'alias_protein_id' --- bin/functions.py | 15 +++++++++------ bin/vcf2gvf.py | 3 ++- 2 files changed, 11 insertions(+), 7 deletions(-) diff --git a/bin/functions.py b/bin/functions.py index 1479eca5..db725d11 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -4,7 +4,7 @@ # standard variables used by all scripts empty_attributes = 'ID=;Name=;alias=;gene=;protein_name=;protein_symbol=;\ - protein_id=;transcript_id=;ps_filter=;ps_exc=; \ + protein_id=;alias_protein_id=;transcript_id=;ps_filter=;ps_exc=; \ mat_pep=;mat_pep_desc=;mat_pep_acc=;ro=;ao=;dp=;sample_size=; \ Reference_seq=;Variant_seq=;nt_name=;aa_name=;hgvs_nt=;hgvs_aa=;hgvs_alias=; \ vcf_gene=;mutation_type=;viral_lineage=;multi_aa_name=; \ @@ -122,15 +122,15 @@ def add_hgvs_names(new_gvf): convert_amino_acid_codes) # fill in 'hgvs_alias' - # add hgvs alias snps to rows with protein_id!=n/a - alias_snp_mask = (new_gvf['alias'].str.contains(aa_snp_regex, regex=True)) & (new_gvf['protein_id']!='n/a') & (new_gvf['alias']!='n/a') + # add hgvs alias snps to rows with alias_protein_id!=n/a + alias_snp_mask = (new_gvf['alias'].str.contains(aa_snp_regex, regex=True)) & (new_gvf['alias_protein_id']!='n/a') & (new_gvf['alias']!='n/a') new_gvf.loc[alias_snp_mask, 'hgvs_alias'] = \ - new_gvf["protein_id"] + ":" + new_gvf.loc[alias_snp_mask, 'alias'].apply( + new_gvf["alias_protein_id"] + ":" + new_gvf.loc[alias_snp_mask, 'alias'].apply( convert_amino_acid_codes) # add hgvs alias names for non-snps - alias_non_snp_mask = (new_gvf['alias'].str.contains(aa_other_regex, regex=True)) & (new_gvf['protein_id']!='n/a') & (new_gvf['alias']!='n/a') + alias_non_snp_mask = (new_gvf['alias'].str.contains(aa_other_regex, regex=True)) & (new_gvf['alias_protein_id']!='n/a') & (new_gvf['alias']!='n/a') new_gvf.loc[alias_non_snp_mask, 'hgvs_alias'] = \ - new_gvf["protein_id"] + ":" + new_gvf.loc[alias_non_snp_mask, 'alias'].apply( + new_gvf["alias_protein_id"] + ":" + new_gvf.loc[alias_non_snp_mask, 'alias'].apply( convert_amino_acid_codes) return(new_gvf) @@ -570,7 +570,10 @@ def add_alias_names(df, GENE_PROTEIN_POSITIONS_DICT): # for each nsp in nsps_list, operate on the number column based on the nsp start coordinates for nsp in nsps_list: nsp_start_aa = int(GENE_PROTEIN_POSITIONS_DICT[nsp]["aa_start"]) + nsp_protein_id = GENE_PROTEIN_POSITIONS_DICT[nsp]["protein_id"] nsp_mask = df['mat_pep']==nsp + # add alias_protein_id + df.loc[nsp_mask, 'alias_protein_id'] = nsp_protein_id # for each half of the mutation name... # update the numeric part df.loc[nsp_mask, '1_newnum'] = df['1_num'].astype(int) - nsp_start_aa + 1 diff --git a/bin/vcf2gvf.py b/bin/vcf2gvf.py index 0e77490c..5037c587 100755 --- a/bin/vcf2gvf.py +++ b/bin/vcf2gvf.py @@ -88,8 +88,9 @@ def vcftogvf(vcf, strain, GENE_PROTEIN_POSITIONS_DICT, sample_size): new_gvf["protein_symbol"] = json_df["protein_symbol"] new_gvf["protein_id"] = json_df["protein_id"] new_gvf["transcript_id"] = json_df["transcript_id"] + new_gvf["alias_protein_id"] = 'n/a' - # add 'alias' column for ORF1a/b mutations + # add 'alias' column for ORF1a/b mutations, and fill in "alias_protein_id" for these as well new_gvf = add_alias_names(new_gvf, GENE_PROTEIN_POSITIONS_DICT) # add clade_defining attribute From e18dfa9db5c4bf70f5619ff0b24adac58d122a8c Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Apr 2024 16:57:36 -0700 Subject: [PATCH 007/161] update nt_delins_regex --- bin/functions.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/bin/functions.py b/bin/functions.py index db725d11..00b046a3 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -84,7 +84,7 @@ def add_hgvs_names(new_gvf): # for ins nt_ins_regex = "[a-z]\\.[0-9\\-_]+ins[A-Z]+" # for delins, eg. g.GCC10182_10184ACA - nt_delins_regex = "[a-z]\\.[A-Z]{2,}[0-9\\-_][A-Z]+" ##not quite right! + nt_delins_regex = "[a-z]\.[A-Z]+-?[0-9]+_-?[0-9]+[A-Z]+" #df.loc[mask, 'val'] = df.loc[mask, 'val'].apply(f) # add hgvs nt snp names From 82f29591d1f7bb034bc14ba6482762ea59d6cf85 Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Apr 2024 17:20:28 -0700 Subject: [PATCH 008/161] add new attribute, 'gene_symbol', from 'gene' in the JSON file --- bin/functions.py | 2 +- bin/vcf2gvf.py | 1 + 2 files changed, 2 insertions(+), 1 deletion(-) diff --git a/bin/functions.py b/bin/functions.py index 00b046a3..53550dc9 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -3,7 +3,7 @@ import logging # standard variables used by all scripts -empty_attributes = 'ID=;Name=;alias=;gene=;protein_name=;protein_symbol=;\ +empty_attributes = 'ID=;Name=;alias=;gene=;gene_symbol=;protein_name=;protein_symbol=;\ protein_id=;alias_protein_id=;transcript_id=;ps_filter=;ps_exc=; \ mat_pep=;mat_pep_desc=;mat_pep_acc=;ro=;ao=;dp=;sample_size=; \ Reference_seq=;Variant_seq=;nt_name=;aa_name=;hgvs_nt=;hgvs_aa=;hgvs_alias=; \ diff --git a/bin/vcf2gvf.py b/bin/vcf2gvf.py index 5037c587..f0c72068 100755 --- a/bin/vcf2gvf.py +++ b/bin/vcf2gvf.py @@ -84,6 +84,7 @@ def vcftogvf(vcf, strain, GENE_PROTEIN_POSITIONS_DICT, sample_size): json_df = map_pos_to_gene_protein( vcf_df['POS'].astype(int), GENE_PROTEIN_POSITIONS_DICT) new_gvf["gene"] = json_df["gene"] + new_gvf["gene_symbol"] = json_df["gene"] new_gvf["protein_name"] = json_df["protein_name"] new_gvf["protein_symbol"] = json_df["protein_symbol"] new_gvf["protein_id"] = json_df["protein_id"] From 418c65dcebc4751df4e1f82b528f602cfabac694 Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Apr 2024 17:25:06 -0700 Subject: [PATCH 009/161] add 'gene_symbol' and 'protein_symbol' columns to mutation index --- bin/update_index_and_logfile.py | 4 +++- 1 file changed, 3 insertions(+), 1 deletion(-) diff --git a/bin/update_index_and_logfile.py b/bin/update_index_and_logfile.py index 703c08da..a0d2f279 100755 --- a/bin/update_index_and_logfile.py +++ b/bin/update_index_and_logfile.py @@ -59,7 +59,9 @@ def gvf2df(gvf): df['alias_protein'] = 'n/a' df.loc[df['alias']!='n/a', 'alias_protein'] = gvf['mat_pep'] df['gene'] = gvf['gene'] + df['gene_symbol'] = gvf['gene_symbol'] df['protein_name'] = gvf['protein_name'] + df['protein_symbol'] = gvf['protein_symbol'] df['Pokay_annotation'] = gvf["function_description"].notna() df['lineages'] = gvf['viral_lineage'] lineage = df['lineages'][0] @@ -82,7 +84,7 @@ def gvf2df(gvf): logfile_df = pd.DataFrame(np.empty((0, 4)), columns=['pos', 'alias', 'new_mutations', 'lineages']) # set mutation index columns - index_cols=['pos', 'mutation', 'hgvs_aa_mutation', 'hgvs_nt_mutation', 'gene', 'protein_name', 'alias', 'hgvs_alias', 'alias_protein', 'Pokay_annotation', 'lineages'] + index_cols=['pos', 'mutation', 'hgvs_aa_mutation', 'hgvs_nt_mutation', 'gene', 'gene_symbol', 'protein_name', 'protein_symbol', 'alias', 'hgvs_alias', 'alias_protein', 'Pokay_annotation', 'lineages'] # open the mutation index if the path was provided if mutation_index_path!=None: From efcce0ce4ab9827eab263737c6d4cd131e5a17de Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Apr 2024 17:26:56 -0700 Subject: [PATCH 010/161] rename 'gene' column in mutation index to 'gene_name' --- bin/update_index_and_logfile.py | 8 ++++---- 1 file changed, 4 insertions(+), 4 deletions(-) diff --git a/bin/update_index_and_logfile.py b/bin/update_index_and_logfile.py index a0d2f279..91321c60 100755 --- a/bin/update_index_and_logfile.py +++ b/bin/update_index_and_logfile.py @@ -58,7 +58,7 @@ def gvf2df(gvf): df['hgvs_alias'] = gvf['hgvs_alias'] df['alias_protein'] = 'n/a' df.loc[df['alias']!='n/a', 'alias_protein'] = gvf['mat_pep'] - df['gene'] = gvf['gene'] + df['gene_name'] = gvf['gene'] df['gene_symbol'] = gvf['gene_symbol'] df['protein_name'] = gvf['protein_name'] df['protein_symbol'] = gvf['protein_symbol'] @@ -84,7 +84,7 @@ def gvf2df(gvf): logfile_df = pd.DataFrame(np.empty((0, 4)), columns=['pos', 'alias', 'new_mutations', 'lineages']) # set mutation index columns - index_cols=['pos', 'mutation', 'hgvs_aa_mutation', 'hgvs_nt_mutation', 'gene', 'gene_symbol', 'protein_name', 'protein_symbol', 'alias', 'hgvs_alias', 'alias_protein', 'Pokay_annotation', 'lineages'] + index_cols=['pos', 'mutation', 'hgvs_aa_mutation', 'hgvs_nt_mutation', 'gene_name', 'gene_symbol', 'protein_name', 'protein_symbol', 'alias', 'hgvs_alias', 'alias_protein', 'Pokay_annotation', 'lineages'] # open the mutation index if the path was provided if mutation_index_path!=None: @@ -121,8 +121,8 @@ def gvf2df(gvf): lineage_mask = mutation_index['lineages'].str.contains(lineage) lineage_chunk = mutation_index.loc[lineage_mask,:].copy() # fill in 'new_mutations' column like: "gene:mutation / nsp:alias" - lineage_chunk['new_mutations'] = lineage_chunk["gene"] + ":" + lineage_chunk["mutation"] - orf1ab_mask = lineage_chunk['gene'].astype(str).str.contains("ORF1ab") + lineage_chunk['new_mutations'] = lineage_chunk["gene_symbol"] + ":" + lineage_chunk["mutation"] + orf1ab_mask = lineage_chunk['gene_symbol'].astype(str).str.contains("ORF1ab") lineage_chunk.loc[orf1ab_mask, 'new_mutations'] = lineage_chunk['new_mutations'] + " / " + lineage_chunk["alias_protein"] + ":" + lineage_chunk["alias"] intergenic_mask = lineage_chunk['protein_name'].astype(str).str.contains("nan") lineage_chunk.loc[intergenic_mask, 'new_mutations'] = lineage_chunk.loc[intergenic_mask, 'new_mutations'].str.replace("nan", "intergenic", regex=True) From 0b6f5e56cc4796e697b37f6535bfe3753f7a55e4 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 30 Apr 2024 13:31:02 -0700 Subject: [PATCH 011/161] change 'protein symbol' column name to 'gene name' to match GVF and mutation index; remove need for JSON file --- bin/functional_annotation.py | 25 +++++-------------------- 1 file changed, 5 insertions(+), 20 deletions(-) diff --git a/bin/functional_annotation.py b/bin/functional_annotation.py index f3b278f1..eb201699 100755 --- a/bin/functional_annotation.py +++ b/bin/functional_annotation.py @@ -31,9 +31,6 @@ def parse_args(): help='versioned reference accession from RefSeq') parser.add_argument('--mutation_index', type=str, required=True, help='index of all mutations (.TSV)') - parser.add_argument('--gene_positions', type=str, - required=True, - help='gene positions in JSON format') parser.add_argument('--outputfile', type=str, required=True, help='output file (.TSV) format') parser.add_argument('--save_dois', type=str, default=None, @@ -188,11 +185,6 @@ def write_tsv(dframe): # Change the directory # os.chdir(path) - # Reading the gene & protein coordinates of SARS-CoV-2 genome - with open(args.gene_positions) as fp: - GENE_PROTEIN_POSITIONS_DICT = json.load(fp) - - dataFrame_cols = ['organism', 'reference accession', 'reference database name', 'nucleotide position', 'original mutation description', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', 'gene name', 'gene symbol', 'protein name', 'protein symbol', 'assay', 'mutation functional effect category', @@ -250,11 +242,13 @@ def write_tsv(dframe): # merge on "mutation" and "gene" in index ("original mutation description" and "gene symbol" in functional annotation file) mutation_index = mutation_index.rename(columns={"mutation": "original mutation description", 'pos':'nucleotide position', 'hgvs_aa_mutation':'amino acid mutation','hgvs_nt_mutation':'nucleotide mutation', - 'gene':'protein symbol', 'protein_name':'protein name', 'hgvs_alias':'amino acid mutation alias'}) + 'gene_name':'gene name', 'gene_symbol':'gene symbol', 'protein_name':'protein name', + 'protein_symbol':'protein symbol', 'hgvs_alias':'amino acid mutation alias'}) # remove doubled columns from dataFrame - index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', 'protein name'] + index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', + 'protein name', 'protein symbol', 'gene name', 'gene symbol'] dataFrame = dataFrame.drop(columns=index_cols_to_use) - merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'protein symbol'], how='left') #, 'alias' + merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'gene name'], how='left') #, 'alias' #dups = mutation_index[mutation_index.duplicated(subset=['nucleotide position', 'original mutation description'], keep=False)] #dups = dups.sort_values(by='nucleotide position') #dups.to_csv('madeline_testing/dups.tsv', sep='\t', index=False) @@ -265,15 +259,6 @@ def write_tsv(dframe): # drop mutations not found in the index merged_dataFrame = merged_dataFrame[merged_dataFrame["nucleotide position"].notna()] - # add gene names and symbols from JSON - ###TO DO: add gene names and symbols to mutation index to simplify this - ###TO DO: these should be ontology names! Need to create a mapping. - ## 'gene symbol' is the same as 'gene name' from the JSON for now - json_df = map_pos_to_gene_protein( - merged_dataFrame["nucleotide position"], GENE_PROTEIN_POSITIONS_DICT) - merged_dataFrame["gene name"] = json_df["gene"] - merged_dataFrame["gene symbol"] = json_df["gene"] - # convert all columns to string type and fillna with empty strings for column in merged_dataFrame.columns: merged_dataFrame[column] = merged_dataFrame[column].astype("string") From c93085c48a61159e7de5d39d5e66ea49d5720001 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 30 Apr 2024 13:50:59 -0700 Subject: [PATCH 012/161] change 'protein symbol' column in df made from Pokay repo to 'gene name' to allow merge with mutation index --- bin/functional_annotation.py | 8 ++++---- 1 file changed, 4 insertions(+), 4 deletions(-) diff --git a/bin/functional_annotation.py b/bin/functional_annotation.py index eb201699..d400c746 100755 --- a/bin/functional_annotation.py +++ b/bin/functional_annotation.py @@ -152,12 +152,12 @@ def extract_metadata(inp_file, chunk, df): function_category] #, comb_mutation, heterozygosity] # print(df_list) df1 = pd.DataFrame( - columns=['original mutation description', 'protein symbol', 'mutation functional effect category']) + columns=['original mutation description', 'gene name', 'mutation functional effect category']) #'comb_mutation', 'heterozygosity']) df1.loc[len(df1)] = df_list df_func['original mutation description'] = df1['original mutation description'].iloc[0] - df_func['protein symbol'] = df1['protein symbol'].iloc[0] + df_func['gene name'] = df1['gene name'].iloc[0] df_func['mutation functional effect category'] = df1['mutation functional effect category'].iloc[0] #df_func['comb_mutation'] = str(df1['comb_mutation'].iloc[0]) #df_func['heterozygosity'] = str(df1['heterozygosity'].iloc[0]) @@ -237,7 +237,7 @@ def write_tsv(dframe): dataFrame = unnest_multi(dataFrame, ["original mutation description"], reset_index=False) dataFrame['index1'] = dataFrame.index - # add HGVS mutations names, nucleotide positions, protein name and protein symbol from mutation index + # add HGVS mutations names, nucleotide positions, protein name, protein symbol, and gene name from mutation index mutation_index = pd.read_csv(args.mutation_index, sep='\t') # merge on "mutation" and "gene" in index ("original mutation description" and "gene symbol" in functional annotation file) mutation_index = mutation_index.rename(columns={"mutation": "original mutation description", 'pos':'nucleotide position', @@ -246,7 +246,7 @@ def write_tsv(dframe): 'protein_symbol':'protein symbol', 'hgvs_alias':'amino acid mutation alias'}) # remove doubled columns from dataFrame index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', - 'protein name', 'protein symbol', 'gene name', 'gene symbol'] + 'protein name', 'protein symbol', 'gene symbol'] dataFrame = dataFrame.drop(columns=index_cols_to_use) merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'gene name'], how='left') #, 'alias' #dups = mutation_index[mutation_index.duplicated(subset=['nucleotide position', 'original mutation description'], keep=False)] From 257d2309c8eb85cd63e8d8ab3830c027b7925180 Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Jul 2024 17:54:16 -0700 Subject: [PATCH 013/161] change 'gene' attribute to 'gene_name' in VCF --- bin/functions.py | 6 +++--- bin/vcf2gvf.py | 4 ++-- 2 files changed, 5 insertions(+), 5 deletions(-) diff --git a/bin/functions.py b/bin/functions.py index 53550dc9..5051c39e 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -3,7 +3,7 @@ import logging # standard variables used by all scripts -empty_attributes = 'ID=;Name=;alias=;gene=;gene_symbol=;protein_name=;protein_symbol=;\ +empty_attributes = 'ID=;Name=;alias=;gene_name=;gene_symbol=;protein_name=;protein_symbol=;\ protein_id=;alias_protein_id=;transcript_id=;ps_filter=;ps_exc=; \ mat_pep=;mat_pep_desc=;mat_pep_acc=;ro=;ao=;dp=;sample_size=; \ Reference_seq=;Variant_seq=;nt_name=;aa_name=;hgvs_nt=;hgvs_aa=;hgvs_alias=; \ @@ -506,7 +506,7 @@ def map_pos_to_gene_protein(pos, GENE_PROTEIN_POSITIONS_DICT): protein_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_alias"] protein_id = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_id"] transcript_id = GENE_PROTEIN_POSITIONS_DICT[entry]["locus_tag"] - + # fill in attributes for mutations in this CDS region cds_mask = df[pos_column].astype(int).between(start, end, inclusive="both") df.loc[cds_mask, "gene"] = gene @@ -542,7 +542,7 @@ def add_alias_names(df, GENE_PROTEIN_POSITIONS_DICT): df.loc[:, 'alias'] = 'n/a' # get list of all NSP, 3CL, and PlPro proteins in the file: - alias_mask = (df['gene'].str.contains("ORF1ab")) & (df['mat_pep']!='n/a') + alias_mask = (df['gene_symbol'].str.contains("ORF1ab")) & (df['mat_pep']!='n/a') nsps_list = sorted(list(set(df[alias_mask]['mat_pep'].tolist()))) if len(nsps_list) > 0: diff --git a/bin/vcf2gvf.py b/bin/vcf2gvf.py index f0c72068..2a65f795 100755 --- a/bin/vcf2gvf.py +++ b/bin/vcf2gvf.py @@ -8,7 +8,7 @@ files. Required user input is a VCF file. The attributes completed by this script are: -['ID', 'Name', 'gene', 'protein_name', 'protein_symbol', 'protein_id', 'ps_filter', 'ps_exc', 'mat_pep', +['ID', 'Name', 'gene_name', 'gene_symbol', 'protein_name', 'protein_symbol', 'protein_id', 'ps_filter', 'ps_exc', 'mat_pep', 'mat_pep_desc','mat_pep_acc', 'ro', 'ao', 'dp', 'sample_size', 'Reference_seq', 'Variant_seq', 'nt_name', 'aa_name', 'hgvs_nt', 'hgvs_aa', 'hgvs_alias', 'vcf_gene', 'mutation_type', 'viral_lineage', 'alternate_frequency', 'transcript_id'] @@ -83,7 +83,7 @@ def vcftogvf(vcf, strain, GENE_PROTEIN_POSITIONS_DICT, sample_size): # add gene and protein attributes from JSON json_df = map_pos_to_gene_protein( vcf_df['POS'].astype(int), GENE_PROTEIN_POSITIONS_DICT) - new_gvf["gene"] = json_df["gene"] + new_gvf["gene_name"] = json_df["gene"] new_gvf["gene_symbol"] = json_df["gene"] new_gvf["protein_name"] = json_df["protein_name"] new_gvf["protein_symbol"] = json_df["protein_symbol"] From f998ed32e7e6ca363a9ead4e42c1ec4ed9220467 Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Jul 2024 18:05:46 -0700 Subject: [PATCH 014/161] change 'gene' to 'gene_name' and add 'gene_symbol' --- bin/gvf2indexandlog.py | 8 +++++--- 1 file changed, 5 insertions(+), 3 deletions(-) diff --git a/bin/gvf2indexandlog.py b/bin/gvf2indexandlog.py index 3aa558b5..27e3829a 100755 --- a/bin/gvf2indexandlog.py +++ b/bin/gvf2indexandlog.py @@ -49,7 +49,7 @@ def parse_args(): # create index from GVF # make empty index df - index_cols=['pos', 'mutation', 'hgvs_aa_mutation', 'hgvs_nt_mutation', 'gene', 'protein_name', 'alias', 'hgvs_alias', 'alias_protein', 'Pokay_annotation', 'lineages'] + index_cols=['pos', 'mutation', 'hgvs_aa_mutation', 'hgvs_nt_mutation', 'gene_name', 'gene_symbol', 'protein_name', 'protein_symbol', 'alias', 'hgvs_alias', 'alias_protein', 'Pokay_annotation', 'lineages'] index = pd.DataFrame(np.empty((gvf.shape[0], len(index_cols))), columns=index_cols) # populate index df with gvf info index['pos'] = gvf['#start'] @@ -60,8 +60,10 @@ def parse_args(): index['hgvs_alias'] = gvf['hgvs_alias'] index['alias_protein'] = 'n/a' index.loc[index['alias']!='n/a', 'alias_protein'] = gvf['mat_pep'] - index['gene'] = gvf['gene'] + index['gene_name'] = gvf['gene_name'] + index['gene_symbol'] = gvf['gene_symbol'] index['protein_name'] = gvf['protein_name'] + index['protein_symbol'] = gvf['protein_symbol'] index['Pokay_annotation'] = gvf["function_description"].notna() index['lineages'] = gvf['viral_lineage'] # tidying @@ -73,7 +75,7 @@ def parse_args(): # create log from index log = index.copy() # fill in 'new_mutations' column like: "gene:mutation" - log['new_mutations'] = log["gene"] + ":" + log["mutation"] + log['new_mutations'] = log["gene_symbol"] + ":" + log["mutation"] # for orf1ab mutations, fill in 'new_mutations' column like: "gene:mutation / nsp:alias" log.loc[log['alias']!='n/a', 'new_mutations'] = log['new_mutations'] + " / " + log["alias_protein"] + ":" + log["alias"] # drop duplicates (there shouldn't be any) From d3174fed3ed6cc6cba1039c79c052571fbb459cb Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Jul 2024 18:08:38 -0700 Subject: [PATCH 015/161] make all args required for log and index creation --- bin/gvf2indexandlog.py | 10 +++++----- 1 file changed, 5 insertions(+), 5 deletions(-) diff --git a/bin/gvf2indexandlog.py b/bin/gvf2indexandlog.py index 27e3829a..fd2e6781 100755 --- a/bin/gvf2indexandlog.py +++ b/bin/gvf2indexandlog.py @@ -18,12 +18,12 @@ def parse_args(): parser = argparse.ArgumentParser( description='Creates an index TSV and a log TSV from one GVF') - parser.add_argument('--gvf_file', type=str, default=None, + parser.add_argument('--gvf_file', type=str, required=True, help='Path to one GVF file to process') - parser.add_argument('--index_savefile', type=str, - default=None, help='Filename to save updated index of all mutations to') - parser.add_argument('--log_savefile', type=str, - default=None, help='Filename to save log to') + parser.add_argument('--index_savefile', type=str, required=True, + help='Filename to save updated index of all mutations to') + parser.add_argument('--log_savefile', type=str, required=True, + help='Filename to save log to') return parser.parse_args() From 0ff02452f95bf7cec07c3b0e710114251222f589 Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Jul 2024 18:53:49 -0700 Subject: [PATCH 016/161] update column names to match DH template, make mutation index optional --- bin/functional_annotation.py | 107 +++++++++++++++++++---------------- 1 file changed, 57 insertions(+), 50 deletions(-) diff --git a/bin/functional_annotation.py b/bin/functional_annotation.py index d400c746..aff3affd 100755 --- a/bin/functional_annotation.py +++ b/bin/functional_annotation.py @@ -29,7 +29,7 @@ def parse_args(): help='directory path for input files') parser.add_argument('--accession', type=str, required=True, help='versioned reference accession from RefSeq') - parser.add_argument('--mutation_index', type=str, required=True, + parser.add_argument('--mutation_index', type=str, default='n/a', help='index of all mutations (.TSV)') parser.add_argument('--outputfile', type=str, required=True, help='output file (.TSV) format') @@ -47,16 +47,16 @@ def combination_mutation(c_mutations, c_mutation): def data_cleanup(dframe): - dframe['mutation functional effect description'] = dframe[ - 'mutation functional effect description'].apply( + dframe['variant functional effect description'] = dframe[ + 'variant functional effect description'].apply( lambda x: ','.join(map(str, x))) - dframe['mutation functional effect description'] = dframe[ - 'mutation functional effect description'].str.replace(',#', '') - dframe['mutation functional effect description'] = dframe[ - 'mutation functional effect description'].str.replace('#', '') - dframe['mutation functional effect description'] = dframe[ - 'mutation functional effect description'].str.strip() + dframe['variant functional effect description'] = dframe[ + 'variant functional effect description'].str.replace(',#', '') + dframe['variant functional effect description'] = dframe[ + 'variant functional effect description'].str.replace('#', '') + dframe['variant functional effect description'] = dframe[ + 'variant functional effect description'].str.strip() #dframe['comb_mutation'] = dframe['comb_mutation'].apply( # lambda x: x[1:-1]) @@ -146,19 +146,19 @@ def extract_metadata(inp_file, chunk, df): del function[chunk[url[index_url - 1]]] df_func = pd.DataFrame(function.items(), columns=['url', - 'mutation functional effect description']) + 'variant functional effect description']) df_list = [mutation_name, gene_name, function_category] #, comb_mutation, heterozygosity] # print(df_list) df1 = pd.DataFrame( - columns=['original mutation description', 'gene name', 'mutation functional effect category']) + columns=['original mutation description', 'gene symbol', 'variant functional effect']) #'comb_mutation', 'heterozygosity']) df1.loc[len(df1)] = df_list df_func['original mutation description'] = df1['original mutation description'].iloc[0] - df_func['gene name'] = df1['gene name'].iloc[0] - df_func['mutation functional effect category'] = df1['mutation functional effect category'].iloc[0] + df_func['gene symbol'] = df1['gene symbol'].iloc[0] + df_func['variant functional effect'] = df1['variant functional effect'].iloc[0] #df_func['comb_mutation'] = str(df1['comb_mutation'].iloc[0]) #df_func['heterozygosity'] = str(df1['heterozygosity'].iloc[0]) @@ -187,8 +187,8 @@ def write_tsv(dframe): dataFrame_cols = ['organism', 'reference accession', 'reference database name', 'nucleotide position', 'original mutation description', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', -'gene name', 'gene symbol', 'protein name', 'protein symbol', 'assay', 'mutation functional effect category', -'mutation functional effect description', 'author', 'publication year', 'URL', 'DOI', 'PMID', +'gene name', 'gene symbol', 'protein name', 'protein symbol', 'variant functional effect', +'variant functional effect description', 'author', 'publication year', 'URL', 'DOI', 'PMID', 'peer review status', 'curator', 'mutation functional annotation resource'] dataFrame = pd.DataFrame(columns=dataFrame_cols) @@ -232,32 +232,47 @@ def write_tsv(dframe): dataFrame['mutation functional annotation resource'] = 'Pokay' - # before merging, unnest the 'original mutation index' column + # strip whitespace + dataFrame["author"] = dataFrame["author"].str.strip() + dataFrame["DOI"] = dataFrame["DOI"].str.strip() + dataFrame["URL"] = dataFrame["URL"].str.strip() + + # add temporary curator name + dataFrame["curator"] = "Paul Gordon" ## for now: need to go through + + # clean up 'peer review status' + dataFrame.loc[dataFrame['peer review status'].isna(), 'peer review status'] = 'false' ##up for debate + dataFrame.loc[dataFrame['peer review status'].str.contains("Journal"), 'peer review status'] = 'true' + dataFrame.loc[dataFrame['peer review status'].str.contains("Preprint"), 'peer review status'] = 'false' + dataFrame.loc[dataFrame['peer review status'].str.contains("Grey literature"), 'peer review status'] = 'false' ##up for debate + + # before merging, unnest the 'original mutation description' column dataFrame["original mutation description"] = dataFrame["original mutation description"].str.split(',') dataFrame = unnest_multi(dataFrame, ["original mutation description"], reset_index=False) dataFrame['index1'] = dataFrame.index - # add HGVS mutations names, nucleotide positions, protein name, protein symbol, and gene name from mutation index - mutation_index = pd.read_csv(args.mutation_index, sep='\t') - # merge on "mutation" and "gene" in index ("original mutation description" and "gene symbol" in functional annotation file) - mutation_index = mutation_index.rename(columns={"mutation": "original mutation description", 'pos':'nucleotide position', - 'hgvs_aa_mutation':'amino acid mutation','hgvs_nt_mutation':'nucleotide mutation', - 'gene_name':'gene name', 'gene_symbol':'gene symbol', 'protein_name':'protein name', - 'protein_symbol':'protein symbol', 'hgvs_alias':'amino acid mutation alias'}) - # remove doubled columns from dataFrame - index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', - 'protein name', 'protein symbol', 'gene symbol'] - dataFrame = dataFrame.drop(columns=index_cols_to_use) - merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'gene name'], how='left') #, 'alias' - #dups = mutation_index[mutation_index.duplicated(subset=['nucleotide position', 'original mutation description'], keep=False)] - #dups = dups.sort_values(by='nucleotide position') - #dups.to_csv('madeline_testing/dups.tsv', sep='\t', index=False) - - # keep only specified columns - merged_dataFrame = merged_dataFrame[['index1'] + dataFrame_cols] - - # drop mutations not found in the index - merged_dataFrame = merged_dataFrame[merged_dataFrame["nucleotide position"].notna()] + # if mutation index: add HGVS mutations names, nucleotide positions, protein names, protein symbols, and gene names from it + if args.mutation_index != 'n/a': + mutation_index = pd.read_csv(args.mutation_index, sep='\t') + # merge on "mutation" and "gene symbol" in index ("original mutation description" and "gene symbol" in functional annotation file) + mutation_index = mutation_index.rename(columns={"mutation": "original mutation description", 'pos':'nucleotide position', + 'hgvs_aa_mutation':'amino acid mutation','hgvs_nt_mutation':'nucleotide mutation', + 'gene_name':'gene name', 'gene_symbol':'gene symbol', 'protein_name':'protein name', + 'protein_symbol':'protein symbol', 'hgvs_alias':'amino acid mutation alias'}) + # remove doubled columns from dataFrame + index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', + 'protein name', 'protein symbol', 'gene name'] + dataFrame = dataFrame.drop(columns=index_cols_to_use) + merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'gene symbol'], how='left') #, 'alias' + #dups = mutation_index[mutation_index.duplicated(subset=['nucleotide position', 'original mutation description'], keep=False)] + #dups = dups.sort_values(by='nucleotide position') + #dups.to_csv('madeline_testing/dups.tsv', sep='\t', index=False) + + # keep only specified columns + merged_dataFrame = merged_dataFrame[['index1'] + dataFrame_cols] + + # drop mutations not found in the index + merged_dataFrame = merged_dataFrame[merged_dataFrame["nucleotide position"].notna()] # convert all columns to string type and fillna with empty strings for column in merged_dataFrame.columns: @@ -267,18 +282,6 @@ def write_tsv(dframe): # convert nucleotide positions to int format (still str) merged_dataFrame["nucleotide position"] = merged_dataFrame["nucleotide position"].str.replace('.0', '', regex=False) - # strip whitespace - merged_dataFrame["author"] = merged_dataFrame["author"].str.strip() - merged_dataFrame["DOI"] = merged_dataFrame["DOI"].str.strip() - merged_dataFrame["URL"] = merged_dataFrame["URL"].str.strip() - - # add temporary curator name, clean up 'peer review status' - merged_dataFrame["curator"] = "Paul Gordon" ## for now: need to go through - merged_dataFrame.loc[merged_dataFrame['peer review status'].isna(), 'peer review status'] = 'unknown' - merged_dataFrame.loc[merged_dataFrame['peer review status'].str.contains("Journal"), 'peer review status'] = 'peer reviewed' - merged_dataFrame.loc[merged_dataFrame['peer review status'].str.contains("Preprint"), 'peer review status'] = 'not peer reviewed' - merged_dataFrame.loc[merged_dataFrame['peer review status'].str.contains("Grey literature"), 'peer review status'] = 'grey literature' - # create agg dictionary to_list = ['original mutation description', 'nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias'] list_dict = dict.fromkeys(to_list, ','.join) @@ -290,6 +293,10 @@ def write_tsv(dframe): # perform groupby and aggregation merged_dataFrame = merged_dataFrame.groupby(by=['index1'], as_index=False).agg(agg_dict) + #remove strings of commas in 'amino acid mutation alias' + merged_dataFrame.loc[merged_dataFrame['amino acid mutation alias'].str.contains(',,', regex=False), 'amino acid mutation alias'] = '' + merged_dataFrame.loc[merged_dataFrame['amino acid mutation alias']==',', 'amino acid mutation alias'] = '' + # reorder columns and drop 'index1' merged_dataFrame = merged_dataFrame[dataFrame_cols] merged_dataFrame = merged_dataFrame.reindex() @@ -301,4 +308,4 @@ def write_tsv(dframe): ###TO DO: modify dois2pmcids.sh to take the whole TSV as input and add PMIDs directly to the TSV to streamline this if args.save_dois != None: dois = merged_dataFrame[merged_dataFrame["DOI"]!=''].drop_duplicates(subset='DOI') - dois["DOI"].to_csv(args.save_dois, header=False, index=False) + dois["DOI"].to_csv(args.save_dois, header=False, index=False) \ No newline at end of file From ed67400dccca0cfd75f7f1af2ca64df00c5db419 Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Jul 2024 19:12:33 -0700 Subject: [PATCH 017/161] fix formatting for non-index file --- bin/functional_annotation.py | 11 ++++++++--- 1 file changed, 8 insertions(+), 3 deletions(-) diff --git a/bin/functional_annotation.py b/bin/functional_annotation.py index aff3affd..93e88b0b 100755 --- a/bin/functional_annotation.py +++ b/bin/functional_annotation.py @@ -274,6 +274,10 @@ def write_tsv(dframe): # drop mutations not found in the index merged_dataFrame = merged_dataFrame[merged_dataFrame["nucleotide position"].notna()] + # allow mutation index to be optional + if args.mutation_index == 'n/a': + merged_dataFrame = dataFrame + # convert all columns to string type and fillna with empty strings for column in merged_dataFrame.columns: merged_dataFrame[column] = merged_dataFrame[column].astype("string") @@ -293,9 +297,10 @@ def write_tsv(dframe): # perform groupby and aggregation merged_dataFrame = merged_dataFrame.groupby(by=['index1'], as_index=False).agg(agg_dict) - #remove strings of commas in 'amino acid mutation alias' - merged_dataFrame.loc[merged_dataFrame['amino acid mutation alias'].str.contains(',,', regex=False), 'amino acid mutation alias'] = '' - merged_dataFrame.loc[merged_dataFrame['amino acid mutation alias']==',', 'amino acid mutation alias'] = '' + #remove strings of commas in mutation name columns + for column in ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias']: + merged_dataFrame.loc[merged_dataFrame[column].str.contains(',,', regex=False), column] = '' + merged_dataFrame.loc[merged_dataFrame[column]==',', column] = '' # reorder columns and drop 'index1' merged_dataFrame = merged_dataFrame[dataFrame_cols] From 28ad84d17367bf4b858e2c78ebf9d2c34a05c071 Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 29 Jul 2024 23:03:19 -0700 Subject: [PATCH 018/161] merge dfs on 'protein symbol' instead --- bin/functional_annotation.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/bin/functional_annotation.py b/bin/functional_annotation.py index 93e88b0b..56ea82b6 100755 --- a/bin/functional_annotation.py +++ b/bin/functional_annotation.py @@ -263,7 +263,7 @@ def write_tsv(dframe): index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', 'protein name', 'protein symbol', 'gene name'] dataFrame = dataFrame.drop(columns=index_cols_to_use) - merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'gene symbol'], how='left') #, 'alias' + merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'protein symbol'], how='left') #, 'alias' #dups = mutation_index[mutation_index.duplicated(subset=['nucleotide position', 'original mutation description'], keep=False)] #dups = dups.sort_values(by='nucleotide position') #dups.to_csv('madeline_testing/dups.tsv', sep='\t', index=False) From 50689b0a70e51c963c64a9205f943b7fa9b07a60 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 30 Jul 2024 00:08:39 -0700 Subject: [PATCH 019/161] sort by nucleotide position --- bin/functional_annotation.py | 13 +++++++++---- 1 file changed, 9 insertions(+), 4 deletions(-) diff --git a/bin/functional_annotation.py b/bin/functional_annotation.py index 56ea82b6..465d87a3 100755 --- a/bin/functional_annotation.py +++ b/bin/functional_annotation.py @@ -152,12 +152,12 @@ def extract_metadata(inp_file, chunk, df): function_category] #, comb_mutation, heterozygosity] # print(df_list) df1 = pd.DataFrame( - columns=['original mutation description', 'gene symbol', 'variant functional effect']) + columns=['original mutation description', 'protein symbol', 'variant functional effect']) #'comb_mutation', 'heterozygosity']) df1.loc[len(df1)] = df_list df_func['original mutation description'] = df1['original mutation description'].iloc[0] - df_func['gene symbol'] = df1['gene symbol'].iloc[0] + df_func['protein symbol'] = df1['protein symbol'].iloc[0] df_func['variant functional effect'] = df1['variant functional effect'].iloc[0] #df_func['comb_mutation'] = str(df1['comb_mutation'].iloc[0]) #df_func['heterozygosity'] = str(df1['heterozygosity'].iloc[0]) @@ -254,15 +254,17 @@ def write_tsv(dframe): # if mutation index: add HGVS mutations names, nucleotide positions, protein names, protein symbols, and gene names from it if args.mutation_index != 'n/a': mutation_index = pd.read_csv(args.mutation_index, sep='\t') - # merge on "mutation" and "gene symbol" in index ("original mutation description" and "gene symbol" in functional annotation file) + # merge on "mutation" and "protein symbol" in index ("original mutation description" and "protein symbol" in functional annotation file) mutation_index = mutation_index.rename(columns={"mutation": "original mutation description", 'pos':'nucleotide position', 'hgvs_aa_mutation':'amino acid mutation','hgvs_nt_mutation':'nucleotide mutation', 'gene_name':'gene name', 'gene_symbol':'gene symbol', 'protein_name':'protein name', 'protein_symbol':'protein symbol', 'hgvs_alias':'amino acid mutation alias'}) # remove doubled columns from dataFrame index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', - 'protein name', 'protein symbol', 'gene name'] + 'protein name', 'gene symbol', 'gene name'] dataFrame = dataFrame.drop(columns=index_cols_to_use) + print('pokay', set(dataFrame['protein symbol'].tolist())) + print('index', set(mutation_index['protein symbol'].tolist())) merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'protein symbol'], how='left') #, 'alias' #dups = mutation_index[mutation_index.duplicated(subset=['nucleotide position', 'original mutation description'], keep=False)] #dups = dups.sort_values(by='nucleotide position') @@ -304,6 +306,9 @@ def write_tsv(dframe): # reorder columns and drop 'index1' merged_dataFrame = merged_dataFrame[dataFrame_cols] + + # sort by nucleotide position and reindex + merged_dataFrame = merged_dataFrame.sort_values(by='nucleotide position') merged_dataFrame = merged_dataFrame.reindex() write_tsv(dframe=merged_dataFrame) From baf3cb0d815de5eebc0c874ebdcbf342f6fca5f8 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 30 Jul 2024 00:16:38 -0700 Subject: [PATCH 020/161] update for new functional annotation format --- bin/addfunctions2gvf.py | 4 ++-- bin/splitmutationnames_functionalannotation.py | 5 ++--- 2 files changed, 4 insertions(+), 5 deletions(-) diff --git a/bin/addfunctions2gvf.py b/bin/addfunctions2gvf.py index 2ae82f00..bed503a2 100755 --- a/bin/addfunctions2gvf.py +++ b/bin/addfunctions2gvf.py @@ -55,8 +55,8 @@ def add_pokay_annotations(gvf, annotation_file): df[column] = df[column].astype(str).str.strip() # merge annotated vcf and functional annotation files by 'Name' and 'protein_symbol' - df = df.rename(columns={"original mutation description": "Name", "amino acid mutation alias":"Pokay_alias", 'mutation functional effect category':"function_category", \ - 'mutation functional effect description':"function_description", 'URL':"source", 'protein symbol':'protein_symbol'}) + df = df.rename(columns={"original mutation description": "Name", "amino acid mutation alias":"Pokay_alias", 'variant functional effect':"function_category", \ + 'variant functional effect description':"function_description", 'URL':"source", 'protein symbol':'protein_symbol'}) df['citation'] = df['author'] + ' et al. (' + df['publication year'].str.replace(".0", "", regex=False) + ')' merged_df = pd.merge(gvf, df, on=['Name', 'protein_symbol'], how='left') #, 'alias' diff --git a/bin/splitmutationnames_functionalannotation.py b/bin/splitmutationnames_functionalannotation.py index 476b4bb7..68c6c1e1 100755 --- a/bin/splitmutationnames_functionalannotation.py +++ b/bin/splitmutationnames_functionalannotation.py @@ -44,8 +44,8 @@ def parse_args(): dataFrame_cols = ['organism', 'reference accession', 'reference database name', 'nucleotide position', 'original mutation description', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', 'comb_mutation', -'gene name', 'gene symbol', 'protein name', 'protein symbol', 'assay', 'mutation functional effect category', -'mutation functional effect description', 'author', 'publication year', 'URL', 'DOI', 'PMID', +'gene name', 'gene symbol', 'protein name', 'protein symbol', 'variant functional effect', +'variant functional effect description', 'author', 'publication year', 'URL', 'DOI', 'PMID', 'peer review status', 'curator', 'mutation functional annotation resource'] # split names in functional annotations file @@ -106,7 +106,6 @@ def parse_args(): df = df[dataFrame_cols] # fix column formats - df['assay'] = df['assay'].str.replace('nan', '', regex=False) df['PMID'] = df['PMID'].str.replace('nan', '', regex=False) df['PMID'] = df['PMID'].str.replace('.0', '', regex=False) df['publication year'] = df['publication year'].str.replace('.0', '', regex=False) From ec976f8413c1ac56da11d44dd5bc258fed439729 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 30 Jul 2024 11:55:32 -0700 Subject: [PATCH 021/161] update to match new functional annotation format --- bin/addfunctions2gvf.py | 7 +++++-- bin/splitmutationnames_gvf.py | 6 ++++-- 2 files changed, 9 insertions(+), 4 deletions(-) diff --git a/bin/addfunctions2gvf.py b/bin/addfunctions2gvf.py index bed503a2..7cf4d2a9 100755 --- a/bin/addfunctions2gvf.py +++ b/bin/addfunctions2gvf.py @@ -50,14 +50,18 @@ def add_pokay_annotations(gvf, annotation_file): # load functional annotations spreadsheet df = pd.read_csv(annotation_file, sep='\t', header=0) + df['author'] = df['author'].fillna('UNKNOWN') # remove any leading/trailing spaces for column in df.columns: + df[column] = df[column].fillna('') df[column] = df[column].astype(str).str.strip() # merge annotated vcf and functional annotation files by 'Name' and 'protein_symbol' - df = df.rename(columns={"original mutation description": "Name", "amino acid mutation alias":"Pokay_alias", 'variant functional effect':"function_category", \ + df = df.rename(columns={"original mutation description": "Name", 'variant functional effect':"function_category", \ 'variant functional effect description':"function_description", 'URL':"source", 'protein symbol':'protein_symbol'}) df['citation'] = df['author'] + ' et al. (' + df['publication year'].str.replace(".0", "", regex=False) + ')' + df_columns = functional_attributes + ["Name", "protein_symbol"] + df = df[df_columns] merged_df = pd.merge(gvf, df, on=['Name', 'protein_symbol'], how='left') #, 'alias' @@ -117,7 +121,6 @@ def add_pokay_annotations(gvf, annotation_file): # replace NaNs in df with empty string merged_df = merged_df.fillna('') - # merge attributes back into a single column merged_df = rejoin_attributes(merged_df, empty_attributes) diff --git a/bin/splitmutationnames_gvf.py b/bin/splitmutationnames_gvf.py index 4a9fb078..7f14f0fd 100755 --- a/bin/splitmutationnames_gvf.py +++ b/bin/splitmutationnames_gvf.py @@ -51,8 +51,10 @@ def parse_args(): # expand #attributes into columns to edit separately gvf = separate_attributes(gvf) - # split names in "Names" attribute into separate rows - gvf = split_names(args.names_to_split, gvf, col_to_split='Name') + # if names_to_split tsv is given, use it to split up the multi-amino acid names + if args.names_to_split != None: + # split names in "Names" attribute into separate rows + gvf = split_names(args.names_to_split, gvf, col_to_split='Name') # rename IDs: rows with the same entry in 'Name' # get the same ID From bfd06d3550b29aa8eb03db5ec15866ab72a6fb7f Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 30 Jul 2024 12:20:59 -0700 Subject: [PATCH 022/161] rename 'alias_protein' to 'mat_pep' --- bin/gvf2indexandlog.py | 7 +++---- 1 file changed, 3 insertions(+), 4 deletions(-) diff --git a/bin/gvf2indexandlog.py b/bin/gvf2indexandlog.py index fd2e6781..9b33d7d7 100755 --- a/bin/gvf2indexandlog.py +++ b/bin/gvf2indexandlog.py @@ -49,7 +49,7 @@ def parse_args(): # create index from GVF # make empty index df - index_cols=['pos', 'mutation', 'hgvs_aa_mutation', 'hgvs_nt_mutation', 'gene_name', 'gene_symbol', 'protein_name', 'protein_symbol', 'alias', 'hgvs_alias', 'alias_protein', 'Pokay_annotation', 'lineages'] + index_cols=['pos', 'mutation', 'hgvs_aa_mutation', 'hgvs_nt_mutation', 'gene_name', 'gene_symbol', 'protein_name', 'protein_symbol', 'alias', 'hgvs_alias', 'mat_pep', 'Pokay_annotation', 'lineages'] index = pd.DataFrame(np.empty((gvf.shape[0], len(index_cols))), columns=index_cols) # populate index df with gvf info index['pos'] = gvf['#start'] @@ -58,8 +58,7 @@ def parse_args(): index['hgvs_nt_mutation'] = gvf['hgvs_nt'] index['alias'] = gvf['alias'] index['hgvs_alias'] = gvf['hgvs_alias'] - index['alias_protein'] = 'n/a' - index.loc[index['alias']!='n/a', 'alias_protein'] = gvf['mat_pep'] + index['mat_pep'] = gvf['mat_pep'] index['gene_name'] = gvf['gene_name'] index['gene_symbol'] = gvf['gene_symbol'] index['protein_name'] = gvf['protein_name'] @@ -77,7 +76,7 @@ def parse_args(): # fill in 'new_mutations' column like: "gene:mutation" log['new_mutations'] = log["gene_symbol"] + ":" + log["mutation"] # for orf1ab mutations, fill in 'new_mutations' column like: "gene:mutation / nsp:alias" - log.loc[log['alias']!='n/a', 'new_mutations'] = log['new_mutations'] + " / " + log["alias_protein"] + ":" + log["alias"] + log.loc[log['alias']!='n/a', 'new_mutations'] = log['new_mutations'] + " / " + log["mat_pep"] + ":" + log["alias"] # drop duplicates (there shouldn't be any) log = log[['pos', 'new_mutations', 'lineages']].drop_duplicates() # drop any NaN rows From 51b3f94bf3fa1bebdb4523fcce8c3fe7c8cdb7a0 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 8 Aug 2024 14:33:20 -0700 Subject: [PATCH 023/161] add Pokay names as 'pokay_id' --- .../NC_045512.2/NC_045512.2.json | 48 ++++++++++++------- 1 file changed, 32 insertions(+), 16 deletions(-) diff --git a/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json b/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json index e2875131..1ae532b3 100644 --- a/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json +++ b/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json @@ -90,7 +90,8 @@ "aa_start": 1, "aa_end": 180, "color": "rgb(128,0,128)", - "protein_alias": "nsp1" + "protein_alias": "nsp1", + "pokay_id": "nsp1" }, "nsp2": { "type": "mature_protein_region_of_CDS", @@ -105,7 +106,8 @@ "aa_start": 181, "aa_end": 818, "color": "rgb(128,0,128)", - "protein_alias": "nsp2" + "protein_alias": "nsp2", + "pokay_id": "nsp2" }, "PL_pro": { "type": "mature_protein_region_of_CDS", @@ -120,7 +122,8 @@ "aa_start": 819, "aa_end": 2763, "color": "rgb(128,0,128)", - "protein_alias": "PL_pro" + "protein_alias": "PL_pro", + "pokay_id": "PLpro" }, "nsp4": { "type": "mature_protein_region_of_CDS", @@ -135,7 +138,8 @@ "aa_start": 2764, "aa_end": 3263, "color": "rgb(128,0,128)", - "protein_alias": "nsp4" + "protein_alias": "nsp4", + "pokay_id": "nsp4" }, "3CL": { "type": "mature_protein_region_of_CDS", @@ -150,7 +154,8 @@ "aa_start": 3264, "aa_end": 3569, "color": "rgb(128,0,128)", - "protein_alias": "3CL" + "protein_alias": "3CL", + "pokay_id": "3CL" }, "nsp6": { "type": "mature_protein_region_of_CDS", @@ -165,7 +170,8 @@ "aa_start": 3570, "aa_end": 3859, "color": "rgb(128,0,128)", - "protein_alias": "nsp6" + "protein_alias": "nsp6", + "pokay_id": "nsp6" }, "nsp7": { "type": "mature_protein_region_of_CDS", @@ -180,7 +186,8 @@ "aa_start": 3860, "aa_end": 3942, "color": "rgb(128,0,128)", - "protein_alias": "nsp7" + "protein_alias": "nsp7", + "pokay_id": "nsp7" }, "nsp8": { "type": "mature_protein_region_of_CDS", @@ -195,7 +202,8 @@ "aa_start": 3943, "aa_end": 4140, "color": "rgb(128,0,128)", - "protein_alias": "nsp8" + "protein_alias": "nsp8", + "pokay_id": "nsp8" }, "nsp9": { "type": "mature_protein_region_of_CDS", @@ -210,7 +218,8 @@ "aa_start": 4141, "aa_end": 4253, "color": "rgb(128,0,128)", - "protein_alias": "nsp9" + "protein_alias": "nsp9", + "pokay_id": "nsp9" }, "nsp10": { "type": "mature_protein_region_of_CDS", @@ -240,7 +249,8 @@ "aa_start": 4393, "aa_end": 5324, "color": "rgb(128,0,128)", - "protein_alias": "RdRp" + "protein_alias": "RdRp", + "pokay_id": "RdRp" }, "nsp13": { "type": "mature_protein_region_of_CDS", @@ -358,7 +368,8 @@ "aa_start": 1, "aa_end": 1273, "color": "rgb(142, 188, 102)", - "protein_alias": "S" + "protein_alias": "S", + "pokay_id": "S" }, "gene-GU280_gp03": { "type": "gene", @@ -388,7 +399,8 @@ "aa_start": 1, "aa_end": 275, "color": "rgb(229, 150, 55)", - "protein_alias": "ORF3a" + "protein_alias": "ORF3a", + "pokay_id": "ORF3a" }, "gene-GU280_gp04": { "type": "gene", @@ -419,7 +431,8 @@ "aa_start": 1, "aa_end": 75, "color": "rgb(170, 189, 82)", - "protein_alias": "E" + "protein_alias": "E", + "pokay_id": "E" }, "gene-GU280_gp05": { "type": "gene", @@ -450,7 +463,8 @@ "aa_start": 1, "aa_end": 222, "color": "rgb(223, 67, 39)", - "protein_alias": "M" + "protein_alias": "M", + "pokay_id": "M" }, "gene-GU280_gp06": { "type": "gene", @@ -480,7 +494,8 @@ "aa_start": 1, "aa_end": 61, "color": "rgb(196, 185, 69)", - "protein_alias": "ORF6" + "protein_alias": "ORF6", + "pokay_id": "ORF6" }, "gene-GU280_gp07": { "type": "gene", @@ -601,7 +616,8 @@ "aa_start": 1, "aa_end": 419, "color": "rgb(80, 151, 186)", - "protein_alias": "N" + "protein_alias": "N", + "pokay_id": "N" }, "gene-GU280_gp11": { "type": "gene", From 2d72b0240de21c2592e9ce24bc6e818711e14c31 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 8 Aug 2024 16:00:08 -0700 Subject: [PATCH 024/161] add missing 'pokay_id' for ORF8 --- assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json | 3 ++- 1 file changed, 2 insertions(+), 1 deletion(-) diff --git a/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json b/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json index 1ae532b3..86c9d1ba 100644 --- a/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json +++ b/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json @@ -585,7 +585,8 @@ "aa_start": 1, "aa_end": 121, "color": "rgb(217, 173, 61)", - "protein_alias": "ORF8" + "protein_alias": "ORF8", + "pokay_id": "ORF8" }, "gene-GU280_gp10": { "type": "gene", From da12255491b2d2379d4d57f4681b6581b9fc9121 Mon Sep 17 00:00:00 2001 From: miseminger Date: Sun, 15 Sep 2024 15:16:36 -0700 Subject: [PATCH 025/161] Add script --- bin/robot2json.py | 93 +++++++++++++++++++++++++++++++++++++++++++++++ 1 file changed, 93 insertions(+) create mode 100644 bin/robot2json.py diff --git a/bin/robot2json.py b/bin/robot2json.py new file mode 100644 index 00000000..f1bbcbd4 --- /dev/null +++ b/bin/robot2json.py @@ -0,0 +1,93 @@ +# temporary code for making JSON files out of ROBOT tables +# ROBOT table: +# example run: +# python robot2json.py --robot "/home/madeline/Downloads/VIRUS-MVP GENEPIO_ROBOT Tables - sc2_gene_protein_data.tsv" --ontology_genes '/home/madeline/Desktop/git_temp/nf-ncov-voc/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_genes.json' --ontology_proteins '/home/madeline/Desktop/git_temp/nf-ncov-voc/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_proteins.json' +# remove orf1a gene name and symbol from TSV as they aren't used in the existing JSON + +import pandas as pd +import json +from json import loads, dumps +import argparse + +def parse_args(): + parser = argparse.ArgumentParser( + description='Converts a annotated VCF file to a GVF ' + 'file with functional annotation') + parser.add_argument('--robot', type=str, default=None, required=True, + help='Path to the modified ROBOT file of gene and protein names and symbols') + parser.add_argument('--ontology_genes', type=str, required=True, + help='Path to save the ontology gene terms JSON to') + parser.add_argument('--ontology_proteins', type=str, required=True, + help='Path to save the ontology protein terms JSON to') + return parser.parse_args() + +if __name__ == '__main__': + + # define args + args = parse_args() + robot_path = args.robot + genes_file_path = args.ontology_genes + proteins_file_path = args.ontology_proteins + + # load ROBOT file + sars = pd.read_csv(robot_path, header=0, sep='\t', usecols=['JSON_match', 'Ontology ID', 'parent class', 'label', 'is about', 'is about label']) + + # process genes + gene_names = sars[sars['parent class'].str.contains("gene name")] + gene_names['gene_name'] = gene_names['label'] + gene_names['gene_name_id'] = gene_names['Ontology ID'] + gene_names['Dbxref'] = gene_names['JSON_match'].str.replace("GeneID", "NCBIGene") + gene_names = gene_names[['Dbxref', 'gene_name', 'gene_name_id', 'is about label']] + + gene_symbols = sars[sars['parent class'].str.contains("gene symbol")] + gene_symbols['gene_symbol'] = gene_symbols['label'] + gene_symbols['gene_symbol_id'] = gene_symbols['Ontology ID'] + gene_symbols = gene_symbols[['gene_symbol', 'gene_symbol_id', 'is about label']] + + genes = pd.merge(gene_names, gene_symbols, on='is about label', how='left') + + # Define a custom function to create a nested structure + def custom_nested_structure_genes(row): + return {row['Dbxref']: {'type': 'gene', 'Dbxref': row['Dbxref'], 'gene_name': {'label': row['gene_name'], 'uri': row['gene_name_id']}, 'gene_symbol': {'label': row['gene_symbol'], 'uri': row['gene_symbol_id']}}} + + # Apply the custom function to each row of the DataFrame + json_data_custom = genes.apply(custom_nested_structure_genes, axis=1).tolist() # saves a list of dicts + json_data = {k: v for d in json_data_custom for k, v in d.items()} # transform to a single dict + + # Convert the dictionary of features to a JSON string + json_str = json.dumps(json_data, indent=4) + + # Write the JSON string to a file + with open(genes_file_path, "w") as genes_json_file: + genes_json_file.write(json_str) + + + # now do proteins + + protein_names = sars[sars['parent class'].str.contains("protein name")] + protein_names['protein_name'] = protein_names['label'] + protein_names['protein_name_id'] = protein_names['Ontology ID'] + protein_names['protein_id'] = protein_names['JSON_match'] + protein_names = protein_names[['protein_id', 'protein_name', 'protein_name_id', 'is about label']] + + protein_symbols = sars[sars['parent class'].str.contains("protein symbol")] + protein_symbols['protein_symbol'] = protein_symbols['label'] + protein_symbols['protein_symbol_id'] = protein_symbols['Ontology ID'] + protein_symbols = protein_symbols[['protein_symbol', 'protein_symbol_id', 'is about label']] + + proteins = pd.merge(protein_names, protein_symbols, on='is about label', how='left') + + # Define a custom function to create a nested structure + def custom_nested_structure_proteins(row): + return {row['protein_id']: {'type': 'CDS', 'protein_id': row['protein_id'], 'protein_name': {'label': row['protein_name'], 'uri': row['protein_name_id']}, 'protein_symbol': {'label': row['protein_symbol'], 'uri': row['protein_symbol_id']}}} + + # Apply the custom function to each row of the DataFrame + json_data_custom = proteins.apply(custom_nested_structure_proteins, axis=1).tolist() # list of dicts + json_data = {k: v for d in json_data_custom for k, v in d.items()} # transform to a single dict + + # Convert the dictionary of features to a JSON string + json_str = json.dumps(json_data, indent=4) + + # Write the JSON string to a file + with open(proteins_file_path, "w") as protein_json_file: + protein_json_file.write(json_str) \ No newline at end of file From 85510531a21b1e32cf1b4a6fde61eecdf2222373 Mon Sep 17 00:00:00 2001 From: miseminger Date: Sun, 15 Sep 2024 15:17:11 -0700 Subject: [PATCH 026/161] Add SARS-CoV-2 ontology terms JSONs --- .../NC_045512.2/NC_045512.2_gene_terms.json | 156 ++++++++++++++++ .../NC_045512.2_ontology_genes.json | 134 ++++++++++++++ .../NC_045512.2_ontology_proteins.json | 134 ++++++++++++++ .../NC_045512.2_protein_terms.json | 170 ++++++++++++++++++ 4 files changed, 594 insertions(+) create mode 100644 assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_gene_terms.json create mode 100644 assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_genes.json create mode 100644 assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_proteins.json create mode 100644 assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_protein_terms.json diff --git a/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_gene_terms.json b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_gene_terms.json new file mode 100644 index 00000000..920553a5 --- /dev/null +++ b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_gene_terms.json @@ -0,0 +1,156 @@ +[ + { + "NCBIGene:43740578": { + "type": "gene", + "Dbxref": "NCBIGene:43740578", + "gene_name": { + "label": "open reading frame 1ab gene (SARS-CoV-2)", + "uri": "GENEPIO:0101134" + }, + "gene_symbol": { + "label": "orf1ab gene (SARS-CoV-2)", + "uri": "GENEPIO:0101135" + } + } + }, + { + "NCBIGene:43740568": { + "type": "gene", + "Dbxref": "NCBIGene:43740568", + "gene_name": { + "label": "surface glycoprotein gene (SARS-CoV-2)", + "uri": "GENEPIO:0101142" + }, + "gene_symbol": { + "label": "s gene (SARS-CoV-2)", + "uri": "GENEPIO:0101143" + } + } + }, + { + "NCBIGene:43740569": { + "type": "gene", + "Dbxref": "NCBIGene:43740569", + "gene_name": { + "label": "open reading frame 3a gene (SARS-CoV-2)", + "uri": "GENEPIO:0101146" + }, + "gene_symbol": { + "label": "orf3a gene (SARS-CoV-2)", + "uri": "GENEPIO:0101147" + } + } + }, + { + "NCBIGene:43740570": { + "type": "gene", + "Dbxref": "NCBIGene:43740570", + "gene_name": { + "label": "envelope gene (SARS-CoV-2)", + "uri": "GENEPIO:0101150" + }, + "gene_symbol": { + "label": "e gene (SARS-CoV-2)", + "uri": "GENEPIO:0101151" + } + } + }, + { + "NCBIGene:43740571": { + "type": "gene", + "Dbxref": "NCBIGene:43740571", + "gene_name": { + "label": "membrane glycoprotein gene (SARS-CoV-2)", + "uri": "GENEPIO:0101154" + }, + "gene_symbol": { + "label": "m gene (SARS-CoV-2)", + "uri": "GENEPIO:0101155" + } + } + }, + { + "NCBIGene:43740572": { + "type": "gene", + "Dbxref": "NCBIGene:43740572", + "gene_name": { + "label": "open reading frame 6 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101158" + }, + "gene_symbol": { + "label": "orf6 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101159" + } + } + }, + { + "NCBIGene:43740573": { + "type": "gene", + "Dbxref": "NCBIGene:43740573", + "gene_name": { + "label": "open reading frame 7a gene (SARS-CoV-2)", + "uri": "GENEPIO:0101162" + }, + "gene_symbol": { + "label": "orf7a gene (SARS-CoV-2)", + "uri": "GENEPIO:0101163" + } + } + }, + { + "NCBIGene:43740574": { + "type": "gene", + "Dbxref": "NCBIGene:43740574", + "gene_name": { + "label": "open reading frame 7b gene (SARS-CoV-2)", + "uri": "GENEPIO:0101166" + }, + "gene_symbol": { + "label": "orf7b gene (SARS-CoV-2)", + "uri": "GENEPIO:0101167" + } + } + }, + { + "NCBIGene:43740577": { + "type": "gene", + "Dbxref": "NCBIGene:43740577", + "gene_name": { + "label": "open reading frame 8 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101170" + }, + "gene_symbol": { + "label": "orf8 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101171" + } + } + }, + { + "NCBIGene:43740575": { + "type": "gene", + "Dbxref": "NCBIGene:43740575", + "gene_name": { + "label": "nucleocapsid phosphoprotein gene (SARS-CoV-2)", + "uri": "GENEPIO:0101174" + }, + "gene_symbol": { + "label": "n gene (SARS-CoV-2)", + "uri": "GENEPIO:0101175" + } + } + }, + { + "NCBIGene:43740576": { + "type": "gene", + "Dbxref": "NCBIGene:43740576", + "gene_name": { + "label": "open reading frame 10 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101178" + }, + "gene_symbol": { + "label": "orf10 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101179" + } + } + } +] \ No newline at end of file diff --git a/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_genes.json b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_genes.json new file mode 100644 index 00000000..971aaf83 --- /dev/null +++ b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_genes.json @@ -0,0 +1,134 @@ +{ + "NCBIGene:43740578": { + "type": "gene", + "Dbxref": "NCBIGene:43740578", + "gene_name": { + "label": "open reading frame 1ab gene (SARS-CoV-2)", + "uri": "GENEPIO:0101134" + }, + "gene_symbol": { + "label": "orf1ab gene (SARS-CoV-2)", + "uri": "GENEPIO:0101135" + } + }, + "NCBIGene:43740568": { + "type": "gene", + "Dbxref": "NCBIGene:43740568", + "gene_name": { + "label": "surface glycoprotein gene (SARS-CoV-2)", + "uri": "GENEPIO:0101142" + }, + "gene_symbol": { + "label": "s gene (SARS-CoV-2)", + "uri": "GENEPIO:0101143" + } + }, + "NCBIGene:43740569": { + "type": "gene", + "Dbxref": "NCBIGene:43740569", + "gene_name": { + "label": "open reading frame 3a gene (SARS-CoV-2)", + "uri": "GENEPIO:0101146" + }, + "gene_symbol": { + "label": "orf3a gene (SARS-CoV-2)", + "uri": "GENEPIO:0101147" + } + }, + "NCBIGene:43740570": { + "type": "gene", + "Dbxref": "NCBIGene:43740570", + "gene_name": { + "label": "envelope gene (SARS-CoV-2)", + "uri": "GENEPIO:0101150" + }, + "gene_symbol": { + "label": "e gene (SARS-CoV-2)", + "uri": "GENEPIO:0101151" + } + }, + "NCBIGene:43740571": { + "type": "gene", + "Dbxref": "NCBIGene:43740571", + "gene_name": { + "label": "membrane glycoprotein gene (SARS-CoV-2)", + "uri": "GENEPIO:0101154" + }, + "gene_symbol": { + "label": "m gene (SARS-CoV-2)", + "uri": "GENEPIO:0101155" + } + }, + "NCBIGene:43740572": { + "type": "gene", + "Dbxref": "NCBIGene:43740572", + "gene_name": { + "label": "open reading frame 6 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101158" + }, + "gene_symbol": { + "label": "orf6 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101159" + } + }, + "NCBIGene:43740573": { + "type": "gene", + "Dbxref": "NCBIGene:43740573", + "gene_name": { + "label": "open reading frame 7a gene (SARS-CoV-2)", + "uri": "GENEPIO:0101162" + }, + "gene_symbol": { + "label": "orf7a gene (SARS-CoV-2)", + "uri": "GENEPIO:0101163" + } + }, + "NCBIGene:43740574": { + "type": "gene", + "Dbxref": "NCBIGene:43740574", + "gene_name": { + "label": "open reading frame 7b gene (SARS-CoV-2)", + "uri": "GENEPIO:0101166" + }, + "gene_symbol": { + "label": "orf7b gene (SARS-CoV-2)", + "uri": "GENEPIO:0101167" + } + }, + "NCBIGene:43740577": { + "type": "gene", + "Dbxref": "NCBIGene:43740577", + "gene_name": { + "label": "open reading frame 8 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101170" + }, + "gene_symbol": { + "label": "orf8 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101171" + } + }, + "NCBIGene:43740575": { + "type": "gene", + "Dbxref": "NCBIGene:43740575", + "gene_name": { + "label": "nucleocapsid phosphoprotein gene (SARS-CoV-2)", + "uri": "GENEPIO:0101174" + }, + "gene_symbol": { + "label": "n gene (SARS-CoV-2)", + "uri": "GENEPIO:0101175" + } + }, + "NCBIGene:43740576": { + "type": "gene", + "Dbxref": "NCBIGene:43740576", + "gene_name": { + "label": "open reading frame 10 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101178" + }, + "gene_symbol": { + "label": "orf10 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101179" + } + } +} \ No newline at end of file diff --git a/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_proteins.json b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_proteins.json new file mode 100644 index 00000000..ea0ffd33 --- /dev/null +++ b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_proteins.json @@ -0,0 +1,134 @@ +{ + "YP_009724389.1": { + "type": "CDS", + "protein_id": "YP_009724389.1", + "protein_name": { + "label": "open reading frame 1a polyprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101140" + }, + "protein_symbol": { + "label": "Orf1a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101141" + } + }, + "YP_009724390.1": { + "type": "CDS", + "protein_id": "YP_009724390.1", + "protein_name": { + "label": "surface glycoprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101144" + }, + "protein_symbol": { + "label": "S protein (SARS-CoV-2)", + "uri": "GENEPIO:0101145" + } + }, + "YP_009724391.1": { + "type": "CDS", + "protein_id": "YP_009724391.1", + "protein_name": { + "label": "open reading frame 3a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101148" + }, + "protein_symbol": { + "label": "Orf3a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101149" + } + }, + "YP_009724392.1": { + "type": "CDS", + "protein_id": "YP_009724392.1", + "protein_name": { + "label": "envelope protein (SARS-CoV-2)", + "uri": "GENEPIO:0101152" + }, + "protein_symbol": { + "label": "E protein (SARS-CoV-2)", + "uri": "GENEPIO:0101153" + } + }, + "YP_009724393.1": { + "type": "CDS", + "protein_id": "YP_009724393.1", + "protein_name": { + "label": "membrane glycoprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101156" + }, + "protein_symbol": { + "label": "M protein (SARS-CoV-2)", + "uri": "GENEPIO:0101157" + } + }, + "YP_009724394.1": { + "type": "CDS", + "protein_id": "YP_009724394.1", + "protein_name": { + "label": "open reading frame 6 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101160" + }, + "protein_symbol": { + "label": "Orf6 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101161" + } + }, + "YP_009724395.1": { + "type": "CDS", + "protein_id": "YP_009724395.1", + "protein_name": { + "label": "open reading frame 7a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101164" + }, + "protein_symbol": { + "label": "Orf7a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101165" + } + }, + "YP_009725318.1": { + "type": "CDS", + "protein_id": "YP_009725318.1", + "protein_name": { + "label": "open reading frame 7b protein (SARS-CoV-2)", + "uri": "GENEPIO:0101168" + }, + "protein_symbol": { + "label": "Orf7b protein (SARS-CoV-2)", + "uri": "GENEPIO:0101169" + } + }, + "YP_009724396.1": { + "type": "CDS", + "protein_id": "YP_009724396.1", + "protein_name": { + "label": "open reading frame 8 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101172" + }, + "protein_symbol": { + "label": "Orf8 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101173" + } + }, + "YP_009724397.2": { + "type": "CDS", + "protein_id": "YP_009724397.2", + "protein_name": { + "label": "nucleocapsid phosphoprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101176" + }, + "protein_symbol": { + "label": "N protein (SARS-CoV-2)", + "uri": "GENEPIO:0101177" + } + }, + "YP_009725255.1": { + "type": "CDS", + "protein_id": "YP_009725255.1", + "protein_name": { + "label": "open reading frame 10 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101180" + }, + "protein_symbol": { + "label": "Orf10 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101181" + } + } +} \ No newline at end of file diff --git a/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_protein_terms.json b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_protein_terms.json new file mode 100644 index 00000000..be4148e7 --- /dev/null +++ b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_protein_terms.json @@ -0,0 +1,170 @@ +[ + { + "YP_009724389.1": { + "type": "CDS", + "protein_id": "YP_009724389.1", + "protein_name": { + "label": "open reading frame 1ab polyprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101136" + }, + "protein_symbol": { + "label": "Orf1ab protein (SARS-CoV-2)", + "uri": "GENEPIO:0101137" + } + } + }, + { + "YP_009724389.1": { + "type": "CDS", + "protein_id": "YP_009724389.1", + "protein_name": { + "label": "open reading frame 1a polyprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101140" + }, + "protein_symbol": { + "label": "Orf1a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101141" + } + } + }, + { + "YP_009724390.1": { + "type": "CDS", + "protein_id": "YP_009724390.1", + "protein_name": { + "label": "surface glycoprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101144" + }, + "protein_symbol": { + "label": "S protein (SARS-CoV-2)", + "uri": "GENEPIO:0101145" + } + } + }, + { + "YP_009724391.1": { + "type": "CDS", + "protein_id": "YP_009724391.1", + "protein_name": { + "label": "open reading frame 3a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101148" + }, + "protein_symbol": { + "label": "Orf3a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101149" + } + } + }, + { + "YP_009724392.1": { + "type": "CDS", + "protein_id": "YP_009724392.1", + "protein_name": { + "label": "envelope protein (SARS-CoV-2)", + "uri": "GENEPIO:0101152" + }, + "protein_symbol": { + "label": "E protein (SARS-CoV-2)", + "uri": "GENEPIO:0101153" + } + } + }, + { + "YP_009724393.1": { + "type": "CDS", + "protein_id": "YP_009724393.1", + "protein_name": { + "label": "membrane glycoprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101156" + }, + "protein_symbol": { + "label": "M protein (SARS-CoV-2)", + "uri": "GENEPIO:0101157" + } + } + }, + { + "YP_009724394.1": { + "type": "CDS", + "protein_id": "YP_009724394.1", + "protein_name": { + "label": "open reading frame 6 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101160" + }, + "protein_symbol": { + "label": "Orf6 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101161" + } + } + }, + { + "YP_009724395.1": { + "type": "CDS", + "protein_id": "YP_009724395.1", + "protein_name": { + "label": "open reading frame 7a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101164" + }, + "protein_symbol": { + "label": "Orf7a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101165" + } + } + }, + { + "YP_009725318.1": { + "type": "CDS", + "protein_id": "YP_009725318.1", + "protein_name": { + "label": "open reading frame 7b protein (SARS-CoV-2)", + "uri": "GENEPIO:0101168" + }, + "protein_symbol": { + "label": "Orf7b protein (SARS-CoV-2)", + "uri": "GENEPIO:0101169" + } + } + }, + { + "YP_009724396.1": { + "type": "CDS", + "protein_id": "YP_009724396.1", + "protein_name": { + "label": "open reading frame 8 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101172" + }, + "protein_symbol": { + "label": "Orf8 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101173" + } + } + }, + { + "YP_009724397.2": { + "type": "CDS", + "protein_id": "YP_009724397.2", + "protein_name": { + "label": "nucleocapsid phosphoprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101176" + }, + "protein_symbol": { + "label": "N protein (SARS-CoV-2)", + "uri": "GENEPIO:0101177" + } + } + }, + { + "YP_009725255.1": { + "type": "CDS", + "protein_id": "YP_009725255.1", + "protein_name": { + "label": "open reading frame 10 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101180" + }, + "protein_symbol": { + "label": "Orf10 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101181" + } + } + } +] \ No newline at end of file From 21d5b6ad741821150f76d233460cbd1ff67c76d3 Mon Sep 17 00:00:00 2001 From: miseminger Date: Sun, 15 Sep 2024 15:28:19 -0700 Subject: [PATCH 027/161] Delete unwanted files --- .../NC_045512.2/NC_045512.2_gene_terms.json | 156 ---------------- .../NC_045512.2_protein_terms.json | 170 ------------------ 2 files changed, 326 deletions(-) delete mode 100644 assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_gene_terms.json delete mode 100644 assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_protein_terms.json diff --git a/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_gene_terms.json b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_gene_terms.json deleted file mode 100644 index 920553a5..00000000 --- a/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_gene_terms.json +++ /dev/null @@ -1,156 +0,0 @@ -[ - { - "NCBIGene:43740578": { - "type": "gene", - "Dbxref": "NCBIGene:43740578", - "gene_name": { - "label": "open reading frame 1ab gene (SARS-CoV-2)", - "uri": "GENEPIO:0101134" - }, - "gene_symbol": { - "label": "orf1ab gene (SARS-CoV-2)", - "uri": "GENEPIO:0101135" - } - } - }, - { - "NCBIGene:43740568": { - "type": "gene", - "Dbxref": "NCBIGene:43740568", - "gene_name": { - "label": "surface glycoprotein gene (SARS-CoV-2)", - "uri": "GENEPIO:0101142" - }, - "gene_symbol": { - "label": "s gene (SARS-CoV-2)", - "uri": "GENEPIO:0101143" - } - } - }, - { - "NCBIGene:43740569": { - "type": "gene", - "Dbxref": "NCBIGene:43740569", - "gene_name": { - "label": "open reading frame 3a gene (SARS-CoV-2)", - "uri": "GENEPIO:0101146" - }, - "gene_symbol": { - "label": "orf3a gene (SARS-CoV-2)", - "uri": "GENEPIO:0101147" - } - } - }, - { - "NCBIGene:43740570": { - "type": "gene", - "Dbxref": "NCBIGene:43740570", - "gene_name": { - "label": "envelope gene (SARS-CoV-2)", - "uri": "GENEPIO:0101150" - }, - "gene_symbol": { - "label": "e gene (SARS-CoV-2)", - "uri": "GENEPIO:0101151" - } - } - }, - { - "NCBIGene:43740571": { - "type": "gene", - "Dbxref": "NCBIGene:43740571", - "gene_name": { - "label": "membrane glycoprotein gene (SARS-CoV-2)", - "uri": "GENEPIO:0101154" - }, - "gene_symbol": { - "label": "m gene (SARS-CoV-2)", - "uri": "GENEPIO:0101155" - } - } - }, - { - "NCBIGene:43740572": { - "type": "gene", - "Dbxref": "NCBIGene:43740572", - "gene_name": { - "label": "open reading frame 6 gene (SARS-CoV-2)", - "uri": "GENEPIO:0101158" - }, - "gene_symbol": { - "label": "orf6 gene (SARS-CoV-2)", - "uri": "GENEPIO:0101159" - } - } - }, - { - "NCBIGene:43740573": { - "type": "gene", - "Dbxref": "NCBIGene:43740573", - "gene_name": { - "label": "open reading frame 7a gene (SARS-CoV-2)", - "uri": "GENEPIO:0101162" - }, - "gene_symbol": { - "label": "orf7a gene (SARS-CoV-2)", - "uri": "GENEPIO:0101163" - } - } - }, - { - "NCBIGene:43740574": { - "type": "gene", - "Dbxref": "NCBIGene:43740574", - "gene_name": { - "label": "open reading frame 7b gene (SARS-CoV-2)", - "uri": "GENEPIO:0101166" - }, - "gene_symbol": { - "label": "orf7b gene (SARS-CoV-2)", - "uri": "GENEPIO:0101167" - } - } - }, - { - "NCBIGene:43740577": { - "type": "gene", - "Dbxref": "NCBIGene:43740577", - "gene_name": { - "label": "open reading frame 8 gene (SARS-CoV-2)", - "uri": "GENEPIO:0101170" - }, - "gene_symbol": { - "label": "orf8 gene (SARS-CoV-2)", - "uri": "GENEPIO:0101171" - } - } - }, - { - "NCBIGene:43740575": { - "type": "gene", - "Dbxref": "NCBIGene:43740575", - "gene_name": { - "label": "nucleocapsid phosphoprotein gene (SARS-CoV-2)", - "uri": "GENEPIO:0101174" - }, - "gene_symbol": { - "label": "n gene (SARS-CoV-2)", - "uri": "GENEPIO:0101175" - } - } - }, - { - "NCBIGene:43740576": { - "type": "gene", - "Dbxref": "NCBIGene:43740576", - "gene_name": { - "label": "open reading frame 10 gene (SARS-CoV-2)", - "uri": "GENEPIO:0101178" - }, - "gene_symbol": { - "label": "orf10 gene (SARS-CoV-2)", - "uri": "GENEPIO:0101179" - } - } - } -] \ No newline at end of file diff --git a/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_protein_terms.json b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_protein_terms.json deleted file mode 100644 index be4148e7..00000000 --- a/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_protein_terms.json +++ /dev/null @@ -1,170 +0,0 @@ -[ - { - "YP_009724389.1": { - "type": "CDS", - "protein_id": "YP_009724389.1", - "protein_name": { - "label": "open reading frame 1ab polyprotein (SARS-CoV-2)", - "uri": "GENEPIO:0101136" - }, - "protein_symbol": { - "label": "Orf1ab protein (SARS-CoV-2)", - "uri": "GENEPIO:0101137" - } - } - }, - { - "YP_009724389.1": { - "type": "CDS", - "protein_id": "YP_009724389.1", - "protein_name": { - "label": "open reading frame 1a polyprotein (SARS-CoV-2)", - "uri": "GENEPIO:0101140" - }, - "protein_symbol": { - "label": "Orf1a protein (SARS-CoV-2)", - "uri": "GENEPIO:0101141" - } - } - }, - { - "YP_009724390.1": { - "type": "CDS", - "protein_id": "YP_009724390.1", - "protein_name": { - "label": "surface glycoprotein (SARS-CoV-2)", - "uri": "GENEPIO:0101144" - }, - "protein_symbol": { - "label": "S protein (SARS-CoV-2)", - "uri": "GENEPIO:0101145" - } - } - }, - { - "YP_009724391.1": { - "type": "CDS", - "protein_id": "YP_009724391.1", - "protein_name": { - "label": "open reading frame 3a protein (SARS-CoV-2)", - "uri": "GENEPIO:0101148" - }, - "protein_symbol": { - "label": "Orf3a protein (SARS-CoV-2)", - "uri": "GENEPIO:0101149" - } - } - }, - { - "YP_009724392.1": { - "type": "CDS", - "protein_id": "YP_009724392.1", - "protein_name": { - "label": "envelope protein (SARS-CoV-2)", - "uri": "GENEPIO:0101152" - }, - "protein_symbol": { - "label": "E protein (SARS-CoV-2)", - "uri": "GENEPIO:0101153" - } - } - }, - { - "YP_009724393.1": { - "type": "CDS", - "protein_id": "YP_009724393.1", - "protein_name": { - "label": "membrane glycoprotein (SARS-CoV-2)", - "uri": "GENEPIO:0101156" - }, - "protein_symbol": { - "label": "M protein (SARS-CoV-2)", - "uri": "GENEPIO:0101157" - } - } - }, - { - "YP_009724394.1": { - "type": "CDS", - "protein_id": "YP_009724394.1", - "protein_name": { - "label": "open reading frame 6 protein (SARS-CoV-2)", - "uri": "GENEPIO:0101160" - }, - "protein_symbol": { - "label": "Orf6 protein (SARS-CoV-2)", - "uri": "GENEPIO:0101161" - } - } - }, - { - "YP_009724395.1": { - "type": "CDS", - "protein_id": "YP_009724395.1", - "protein_name": { - "label": "open reading frame 7a protein (SARS-CoV-2)", - "uri": "GENEPIO:0101164" - }, - "protein_symbol": { - "label": "Orf7a protein (SARS-CoV-2)", - "uri": "GENEPIO:0101165" - } - } - }, - { - "YP_009725318.1": { - "type": "CDS", - "protein_id": "YP_009725318.1", - "protein_name": { - "label": "open reading frame 7b protein (SARS-CoV-2)", - "uri": "GENEPIO:0101168" - }, - "protein_symbol": { - "label": "Orf7b protein (SARS-CoV-2)", - "uri": "GENEPIO:0101169" - } - } - }, - { - "YP_009724396.1": { - "type": "CDS", - "protein_id": "YP_009724396.1", - "protein_name": { - "label": "open reading frame 8 protein (SARS-CoV-2)", - "uri": "GENEPIO:0101172" - }, - "protein_symbol": { - "label": "Orf8 protein (SARS-CoV-2)", - "uri": "GENEPIO:0101173" - } - } - }, - { - "YP_009724397.2": { - "type": "CDS", - "protein_id": "YP_009724397.2", - "protein_name": { - "label": "nucleocapsid phosphoprotein (SARS-CoV-2)", - "uri": "GENEPIO:0101176" - }, - "protein_symbol": { - "label": "N protein (SARS-CoV-2)", - "uri": "GENEPIO:0101177" - } - } - }, - { - "YP_009725255.1": { - "type": "CDS", - "protein_id": "YP_009725255.1", - "protein_name": { - "label": "open reading frame 10 protein (SARS-CoV-2)", - "uri": "GENEPIO:0101180" - }, - "protein_symbol": { - "label": "Orf10 protein (SARS-CoV-2)", - "uri": "GENEPIO:0101181" - } - } - } -] \ No newline at end of file From e6592d279b2f24bb4e3da47aff299323c85470d4 Mon Sep 17 00:00:00 2001 From: miseminger Date: Sun, 15 Sep 2024 17:19:37 -0700 Subject: [PATCH 028/161] upload script --- bin/addontologyterms2json.py | 72 ++++++++++++++++++++++++++++++++++++ 1 file changed, 72 insertions(+) create mode 100644 bin/addontologyterms2json.py diff --git a/bin/addontologyterms2json.py b/bin/addontologyterms2json.py new file mode 100644 index 00000000..0a90c292 --- /dev/null +++ b/bin/addontologyterms2json.py @@ -0,0 +1,72 @@ +# This script adds the ontology terms in assets/virus_ontologyTerms to the master JSON file. The added keys are 'gene_name', 'gene_symbol', 'protein_name', and 'protein_symbol'. +#Example run: +#python addontologyterms2json.py --gene_positions ~/Downloads/NC_045512.2.json --ontology_genes ../assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_genes.json --ontology_proteins ../assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_proteins.json --savefile NC_045512.2_ontologytermsadded.json + +import json +import argparse + +def parse_args(): + parser = argparse.ArgumentParser( + description='Converts a annotated VCF file to a GVF ' + 'file with functional annotation') + parser.add_argument('--gene_positions', type=str, default=None, required=True, + help='Path to the JSON file of gene positions to add ontology terms to') + parser.add_argument('--ontology_genes', type=str, required=True, + help='Path to the ontology gene terms file') + parser.add_argument('--ontology_proteins', type=str, required=True, + help='Path to the ontology protein terms file') + parser.add_argument('--savefile', type=str, required=True, + help='Filename for the output JSON file') + return parser.parse_args() + +if __name__ == '__main__': + + # define args + args = parse_args() + gene_positions = args.gene_positions + ontology_genes = args.ontology_genes + ontology_proteins = args.ontology_proteins + savefile = args.savefile + + # Open the gene_positions JSON file + with open(gene_positions) as fp: + GENE_PROTEIN_POSITIONS_DICT = json.load(fp) + + # Open the ontology_genes JSON file + with open(ontology_genes) as fp: + ONTOLOGY_GENES_DICT = json.load(fp) + + # Open the ontology_proteins JSON file + with open(ontology_proteins) as fp: + ONTOLOGY_PROTEINS_DICT = json.load(fp) + + # loop through all CDS and gene regions in gene_positions + for entry in GENE_PROTEIN_POSITIONS_DICT.keys(): + + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="CDS": + protein_id = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_id"] + # find matching CDS entry in ontology_proteins JSON + for protein_entry in ONTOLOGY_PROTEINS_DICT.keys(): + if ONTOLOGY_PROTEINS_DICT[protein_entry]["protein_id"] == protein_id: + protein_name = ONTOLOGY_PROTEINS_DICT[protein_entry]["protein_name"] + protein_symbol = ONTOLOGY_PROTEINS_DICT[protein_entry]["protein_symbol"] + GENE_PROTEIN_POSITIONS_DICT[entry]["protein_name"] = protein_name + GENE_PROTEIN_POSITIONS_DICT[entry]["protein_symbol"] = protein_symbol + + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="gene": + gene_ids = GENE_PROTEIN_POSITIONS_DICT[entry]["Dbxref"].replace("GeneID", "NCBIGene") + # find matching CDS entry in ontology_proteins JSON + for gene_entry in ONTOLOGY_GENES_DICT.keys(): + if ONTOLOGY_GENES_DICT[gene_entry]["Dbxref"] == gene_ids: + gene_name = ONTOLOGY_GENES_DICT[gene_entry]["gene_name"] + gene_symbol = ONTOLOGY_GENES_DICT[gene_entry]["gene_symbol"] + GENE_PROTEIN_POSITIONS_DICT[entry]["gene_name"] = gene_name + GENE_PROTEIN_POSITIONS_DICT[entry]["gene_symbol"] = gene_symbol + + + # Convert the dictionary of features to a JSON string + json_str = json.dumps(GENE_PROTEIN_POSITIONS_DICT, indent=4) + + # Write the JSON string to a file + with open(savefile, "w") as json_file: + json_file.write(json_str) \ No newline at end of file From 54bb4ac033c309c959f2b887e129f3aecf2707a1 Mon Sep 17 00:00:00 2001 From: miseminger Date: Sun, 15 Sep 2024 17:21:03 -0700 Subject: [PATCH 029/161] update comment --- bin/addontologyterms2json.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/bin/addontologyterms2json.py b/bin/addontologyterms2json.py index 0a90c292..06f3ec00 100644 --- a/bin/addontologyterms2json.py +++ b/bin/addontologyterms2json.py @@ -55,7 +55,7 @@ def parse_args(): if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="gene": gene_ids = GENE_PROTEIN_POSITIONS_DICT[entry]["Dbxref"].replace("GeneID", "NCBIGene") - # find matching CDS entry in ontology_proteins JSON + # find matching gene entry in ontology_genes JSON for gene_entry in ONTOLOGY_GENES_DICT.keys(): if ONTOLOGY_GENES_DICT[gene_entry]["Dbxref"] == gene_ids: gene_name = ONTOLOGY_GENES_DICT[gene_entry]["gene_name"] From 8955e30d1b2a9734a4c80a13f72d52162f467e54 Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 16 Sep 2024 17:38:14 -0700 Subject: [PATCH 030/161] Add ontology terms to JSON, and remove pokay_id --- .../NC_045512.2/NC_045512.2.json | 255 +++++++++++++++--- 1 file changed, 211 insertions(+), 44 deletions(-) diff --git a/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json b/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json index 86c9d1ba..e843ec26 100644 --- a/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json +++ b/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json @@ -35,7 +35,15 @@ "gbkey": "Gene", "gene": "ORF1ab", "gene_biotype": "protein_coding", - "locus_tag": "GU280_gp01" + "locus_tag": "GU280_gp01", + "gene_name": { + "label": "open reading frame 1ab gene (SARS-CoV-2)", + "uri": "GENEPIO:0101134" + }, + "gene_symbol": { + "label": "orf1ab gene (SARS-CoV-2)", + "uri": "GENEPIO:0101135" + } }, "ORF1a": { "type": "CDS", @@ -55,7 +63,15 @@ "aa_start": 1, "aa_end": 4400, "color": "rgb(217, 173, 61)", - "protein_alias": "ORF1a" + "protein_alias": "ORF1a", + "protein_name": { + "label": "open reading frame 1a polyprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101140" + }, + "protein_symbol": { + "label": "Orf1a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101141" + } }, "ORF1b": { "type": "CDS", @@ -75,7 +91,15 @@ "aa_start": 1, "aa_end": 2695, "color": "rgb(80, 151, 186)", - "protein_alias": "ORF1b" + "protein_alias": "ORF1b", + "protein_name": { + "label": "open reading frame 1a polyprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101140" + }, + "protein_symbol": { + "label": "Orf1a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101141" + } }, "nsp1": { "type": "mature_protein_region_of_CDS", @@ -90,8 +114,7 @@ "aa_start": 1, "aa_end": 180, "color": "rgb(128,0,128)", - "protein_alias": "nsp1", - "pokay_id": "nsp1" + "protein_alias": "nsp1" }, "nsp2": { "type": "mature_protein_region_of_CDS", @@ -106,8 +129,7 @@ "aa_start": 181, "aa_end": 818, "color": "rgb(128,0,128)", - "protein_alias": "nsp2", - "pokay_id": "nsp2" + "protein_alias": "nsp2" }, "PL_pro": { "type": "mature_protein_region_of_CDS", @@ -122,8 +144,7 @@ "aa_start": 819, "aa_end": 2763, "color": "rgb(128,0,128)", - "protein_alias": "PL_pro", - "pokay_id": "PLpro" + "protein_alias": "PL_pro" }, "nsp4": { "type": "mature_protein_region_of_CDS", @@ -138,8 +159,7 @@ "aa_start": 2764, "aa_end": 3263, "color": "rgb(128,0,128)", - "protein_alias": "nsp4", - "pokay_id": "nsp4" + "protein_alias": "nsp4" }, "3CL": { "type": "mature_protein_region_of_CDS", @@ -154,8 +174,7 @@ "aa_start": 3264, "aa_end": 3569, "color": "rgb(128,0,128)", - "protein_alias": "3CL", - "pokay_id": "3CL" + "protein_alias": "3CL" }, "nsp6": { "type": "mature_protein_region_of_CDS", @@ -170,8 +189,7 @@ "aa_start": 3570, "aa_end": 3859, "color": "rgb(128,0,128)", - "protein_alias": "nsp6", - "pokay_id": "nsp6" + "protein_alias": "nsp6" }, "nsp7": { "type": "mature_protein_region_of_CDS", @@ -186,8 +204,7 @@ "aa_start": 3860, "aa_end": 3942, "color": "rgb(128,0,128)", - "protein_alias": "nsp7", - "pokay_id": "nsp7" + "protein_alias": "nsp7" }, "nsp8": { "type": "mature_protein_region_of_CDS", @@ -202,8 +219,7 @@ "aa_start": 3943, "aa_end": 4140, "color": "rgb(128,0,128)", - "protein_alias": "nsp8", - "pokay_id": "nsp8" + "protein_alias": "nsp8" }, "nsp9": { "type": "mature_protein_region_of_CDS", @@ -218,8 +234,7 @@ "aa_start": 4141, "aa_end": 4253, "color": "rgb(128,0,128)", - "protein_alias": "nsp9", - "pokay_id": "nsp9" + "protein_alias": "nsp9" }, "nsp10": { "type": "mature_protein_region_of_CDS", @@ -249,8 +264,7 @@ "aa_start": 4393, "aa_end": 5324, "color": "rgb(128,0,128)", - "protein_alias": "RdRp", - "pokay_id": "RdRp" + "protein_alias": "RdRp" }, "nsp13": { "type": "mature_protein_region_of_CDS", @@ -349,7 +363,15 @@ "gene": "S", "gene_biotype": "protein_coding", "gene_synonym": "spike glycoprotein", - "locus_tag": "GU280_gp02" + "locus_tag": "GU280_gp02", + "gene_name": { + "label": "surface glycoprotein gene (SARS-CoV-2)", + "uri": "GENEPIO:0101142" + }, + "gene_symbol": { + "label": "s gene (SARS-CoV-2)", + "uri": "GENEPIO:0101143" + } }, "S": { "type": "CDS", @@ -369,7 +391,14 @@ "aa_end": 1273, "color": "rgb(142, 188, 102)", "protein_alias": "S", - "pokay_id": "S" + "protein_name": { + "label": "surface glycoprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101144" + }, + "protein_symbol": { + "label": "S protein (SARS-CoV-2)", + "uri": "GENEPIO:0101145" + } }, "gene-GU280_gp03": { "type": "gene", @@ -381,7 +410,15 @@ "gbkey": "Gene", "gene": "ORF3a", "gene_biotype": "protein_coding", - "locus_tag": "GU280_gp03" + "locus_tag": "GU280_gp03", + "gene_name": { + "label": "open reading frame 3a gene (SARS-CoV-2)", + "uri": "GENEPIO:0101146" + }, + "gene_symbol": { + "label": "orf3a gene (SARS-CoV-2)", + "uri": "GENEPIO:0101147" + } }, "ORF3a": { "type": "CDS", @@ -400,7 +437,14 @@ "aa_end": 275, "color": "rgb(229, 150, 55)", "protein_alias": "ORF3a", - "pokay_id": "ORF3a" + "protein_name": { + "label": "open reading frame 3a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101148" + }, + "protein_symbol": { + "label": "Orf3a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101149" + } }, "gene-GU280_gp04": { "type": "gene", @@ -412,7 +456,15 @@ "gbkey": "Gene", "gene": "E", "gene_biotype": "protein_coding", - "locus_tag": "GU280_gp04" + "locus_tag": "GU280_gp04", + "gene_name": { + "label": "envelope gene (SARS-CoV-2)", + "uri": "GENEPIO:0101150" + }, + "gene_symbol": { + "label": "e gene (SARS-CoV-2)", + "uri": "GENEPIO:0101151" + } }, "E": { "type": "CDS", @@ -432,7 +484,14 @@ "aa_end": 75, "color": "rgb(170, 189, 82)", "protein_alias": "E", - "pokay_id": "E" + "protein_name": { + "label": "envelope protein (SARS-CoV-2)", + "uri": "GENEPIO:0101152" + }, + "protein_symbol": { + "label": "E protein (SARS-CoV-2)", + "uri": "GENEPIO:0101153" + } }, "gene-GU280_gp05": { "type": "gene", @@ -444,7 +503,15 @@ "gbkey": "Gene", "gene": "M", "gene_biotype": "protein_coding", - "locus_tag": "GU280_gp05" + "locus_tag": "GU280_gp05", + "gene_name": { + "label": "membrane glycoprotein gene (SARS-CoV-2)", + "uri": "GENEPIO:0101154" + }, + "gene_symbol": { + "label": "m gene (SARS-CoV-2)", + "uri": "GENEPIO:0101155" + } }, "M": { "type": "CDS", @@ -464,7 +531,14 @@ "aa_end": 222, "color": "rgb(223, 67, 39)", "protein_alias": "M", - "pokay_id": "M" + "protein_name": { + "label": "membrane glycoprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101156" + }, + "protein_symbol": { + "label": "M protein (SARS-CoV-2)", + "uri": "GENEPIO:0101157" + } }, "gene-GU280_gp06": { "type": "gene", @@ -476,7 +550,15 @@ "gbkey": "Gene", "gene": "ORF6", "gene_biotype": "protein_coding", - "locus_tag": "GU280_gp06" + "locus_tag": "GU280_gp06", + "gene_name": { + "label": "open reading frame 6 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101158" + }, + "gene_symbol": { + "label": "orf6 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101159" + } }, "ORF6": { "type": "CDS", @@ -495,7 +577,14 @@ "aa_end": 61, "color": "rgb(196, 185, 69)", "protein_alias": "ORF6", - "pokay_id": "ORF6" + "protein_name": { + "label": "open reading frame 6 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101160" + }, + "protein_symbol": { + "label": "Orf6 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101161" + } }, "gene-GU280_gp07": { "type": "gene", @@ -507,7 +596,15 @@ "gbkey": "Gene", "gene": "ORF7a", "gene_biotype": "protein_coding", - "locus_tag": "GU280_gp07" + "locus_tag": "GU280_gp07", + "gene_name": { + "label": "open reading frame 7a gene (SARS-CoV-2)", + "uri": "GENEPIO:0101162" + }, + "gene_symbol": { + "label": "orf7a gene (SARS-CoV-2)", + "uri": "GENEPIO:0101163" + } }, "ORF7a": { "type": "CDS", @@ -525,7 +622,15 @@ "aa_start": 1, "aa_end": 121, "color": "rgb(117, 182, 129)", - "protein_alias": "ORF7a" + "protein_alias": "ORF7a", + "protein_name": { + "label": "open reading frame 7a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101164" + }, + "protein_symbol": { + "label": "Orf7a protein (SARS-CoV-2)", + "uri": "GENEPIO:0101165" + } }, "gene-GU280_gp08": { "type": "gene", @@ -537,7 +642,15 @@ "gbkey": "Gene", "gene": "ORF7b", "gene_biotype": "protein_coding", - "locus_tag": "GU280_gp08" + "locus_tag": "GU280_gp08", + "gene_name": { + "label": "open reading frame 7b gene (SARS-CoV-2)", + "uri": "GENEPIO:0101166" + }, + "gene_symbol": { + "label": "orf7b gene (SARS-CoV-2)", + "uri": "GENEPIO:0101167" + } }, "ORF7b": { "type": "CDS", @@ -555,7 +668,15 @@ "aa_start": 1, "aa_end": 43, "color": "rgb(96, 170, 158)", - "protein_alias": "ORF7b" + "protein_alias": "ORF7b", + "protein_name": { + "label": "open reading frame 7b protein (SARS-CoV-2)", + "uri": "GENEPIO:0101168" + }, + "protein_symbol": { + "label": "Orf7b protein (SARS-CoV-2)", + "uri": "GENEPIO:0101169" + } }, "gene-GU280_gp09": { "type": "gene", @@ -567,7 +688,15 @@ "gbkey": "Gene", "gene": "ORF8", "gene_biotype": "protein_coding", - "locus_tag": "GU280_gp09" + "locus_tag": "GU280_gp09", + "gene_name": { + "label": "open reading frame 8 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101170" + }, + "gene_symbol": { + "label": "orf8 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101171" + } }, "ORF8": { "type": "CDS", @@ -586,7 +715,14 @@ "aa_end": 121, "color": "rgb(217, 173, 61)", "protein_alias": "ORF8", - "pokay_id": "ORF8" + "protein_name": { + "label": "open reading frame 8 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101172" + }, + "protein_symbol": { + "label": "Orf8 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101173" + } }, "gene-GU280_gp10": { "type": "gene", @@ -598,7 +734,15 @@ "gbkey": "Gene", "gene": "N", "gene_biotype": "protein_coding", - "locus_tag": "GU280_gp10" + "locus_tag": "GU280_gp10", + "gene_name": { + "label": "nucleocapsid phosphoprotein gene (SARS-CoV-2)", + "uri": "GENEPIO:0101174" + }, + "gene_symbol": { + "label": "n gene (SARS-CoV-2)", + "uri": "GENEPIO:0101175" + } }, "N": { "type": "CDS", @@ -618,7 +762,14 @@ "aa_end": 419, "color": "rgb(80, 151, 186)", "protein_alias": "N", - "pokay_id": "N" + "protein_name": { + "label": "nucleocapsid phosphoprotein (SARS-CoV-2)", + "uri": "GENEPIO:0101176" + }, + "protein_symbol": { + "label": "N protein (SARS-CoV-2)", + "uri": "GENEPIO:0101177" + } }, "gene-GU280_gp11": { "type": "gene", @@ -630,7 +781,15 @@ "gbkey": "Gene", "gene": "ORF10", "gene_biotype": "protein_coding", - "locus_tag": "GU280_gp11" + "locus_tag": "GU280_gp11", + "gene_name": { + "label": "open reading frame 10 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101178" + }, + "gene_symbol": { + "label": "orf10 gene (SARS-CoV-2)", + "uri": "GENEPIO:0101179" + } }, "ORF10": { "type": "CDS", @@ -648,7 +807,15 @@ "aa_start": 1, "aa_end": 38, "color": "rgb(230, 112, 48)", - "protein_alias": "ORF10" + "protein_alias": "ORF10", + "protein_name": { + "label": "open reading frame 10 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101180" + }, + "protein_symbol": { + "label": "Orf10 protein (SARS-CoV-2)", + "uri": "GENEPIO:0101181" + } }, "3'UTR": { "type": "three_prime_UTR", @@ -662,4 +829,4 @@ "type": "INTERGENIC", "color": "rgb(128,128,128)" } -} \ No newline at end of file +} From 4c66d82142d46a70fb9cfc5110b9efd76442b19e Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 17 Sep 2024 01:55:30 -0700 Subject: [PATCH 031/161] add aliases from Sept 9 issue --- .../NC_045512.2/NC_045512.2_key.json | 56 +++++++++---------- 1 file changed, 28 insertions(+), 28 deletions(-) diff --git a/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json b/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json index 3b0cf21d..5467c295 100644 --- a/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json +++ b/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json @@ -1,30 +1,30 @@ { - "ORF1ab polyprotein" : "ORF1a", - "ORF1ab polyprotein-i" : "ORF1b", - "ORF3a protein" : "ORF3a", - "ORF6 protein" : "ORF6", - "ORF7a protein" : "ORF7a", - "ORF7b" : "ORF7b", - "ORF8 protein" : "ORF8", - "ORF10 protein" : "ORF10", - "envelope protein" : "E", - "membrane glycoprotein" : "M", - "nucleocapsid phosphoprotein" : "N", - "surface glycoprotein" : "S", - "3C-like proteinase" : "3CL", - "leader protein" : "nsp1", - "RNA-dependent RNA polymerase" : "RdRp", - "helicase" : "nsp13", - "3'-to-5' exonuclease" : "nsp14", - "2'-O-ribose methyltransferase" : "nsp16", - "nsp3" : "PL_pro", - "nsp2" : "nsp2", - "nsp4" : "nsp4", - "nsp6" : "nsp6", - "nsp7" : "nsp7", - "nsp8" : "nsp8", - "nsp9" : "nsp9", - "nsp10" : "nsp10", - "nsp11" : "nsp11", - "endoRNAse" : "nsp15" + "ORF1ab polyprotein" : ["ORF1a"], + "ORF1ab polyprotein-i" : ["ORF1b", "ORF1ab"], + "ORF3a protein" : ["ORF3a"], + "ORF6 protein" : ["ORF6"], + "ORF7a protein" : ["ORF7a"], + "ORF7b" : ["ORF7b"], + "ORF8 protein" : ["ORF8"], + "ORF10 protein" : ["ORF10"], + "envelope protein" : ["E"], + "membrane glycoprotein" : ["M"], + "nucleocapsid phosphoprotein" : ["N"], + "surface glycoprotein" : ["S"], + "3C-like proteinase" : ["3CL"], + "leader protein" : ["nsp1"], + "RNA-dependent RNA polymerase" : ["nsp12"], + "helicase" : ["nsp13"], + "3'-to-5' exonuclease" : ["nsp14"], + "2'-O-ribose methyltransferase" : ["nsp16"], + "nsp3" : ["PL_pro"], + "nsp2" : ["nsp2"], + "nsp4" : ["nsp4"], + "nsp6" : ["nsp6"], + "nsp7" : ["nsp7"], + "nsp8" : ["nsp8"], + "nsp9" : ["nsp9"], + "nsp10" : ["nsp10"], + "nsp11" : ["nsp11"], + "endoRNAse" : ["nsp15"] } From b1df7ffe75a8e7f5f233cc3a1bd6a10add7d6af4 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 17 Sep 2024 02:06:28 -0700 Subject: [PATCH 032/161] remove alias names that are the same as the gene name --- .../NC_045512.2/NC_045512.2_key.json | 20 +++++++++---------- 1 file changed, 10 insertions(+), 10 deletions(-) diff --git a/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json b/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json index 5467c295..f32f582b 100644 --- a/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json +++ b/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json @@ -1,16 +1,16 @@ { "ORF1ab polyprotein" : ["ORF1a"], "ORF1ab polyprotein-i" : ["ORF1b", "ORF1ab"], - "ORF3a protein" : ["ORF3a"], - "ORF6 protein" : ["ORF6"], - "ORF7a protein" : ["ORF7a"], - "ORF7b" : ["ORF7b"], - "ORF8 protein" : ["ORF8"], - "ORF10 protein" : ["ORF10"], - "envelope protein" : ["E"], - "membrane glycoprotein" : ["M"], - "nucleocapsid phosphoprotein" : ["N"], - "surface glycoprotein" : ["S"], + "ORF3a protein" : [], + "ORF6 protein" : [], + "ORF7a protein" : [], + "ORF7b" : [], + "ORF8 protein" : [], + "ORF10 protein" : [], + "envelope protein" : [], + "membrane glycoprotein" : [], + "nucleocapsid phosphoprotein" : [], + "surface glycoprotein" : [], "3C-like proteinase" : ["3CL"], "leader protein" : ["nsp1"], "RNA-dependent RNA polymerase" : ["nsp12"], From 9303eb815f95cab468e0df6920ad8722098fe4c8 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 17 Sep 2024 23:24:00 -0700 Subject: [PATCH 033/161] Temporarily add Pokay name for PLpro to aliases --- assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json b/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json index f32f582b..0c41208a 100644 --- a/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json +++ b/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json @@ -17,7 +17,7 @@ "helicase" : ["nsp13"], "3'-to-5' exonuclease" : ["nsp14"], "2'-O-ribose methyltransferase" : ["nsp16"], - "nsp3" : ["PL_pro"], + "nsp3" : ["PL_pro", "PLpro"], "nsp2" : ["nsp2"], "nsp4" : ["nsp4"], "nsp6" : ["nsp6"], From d13e2cc9809e2e6e4bae6b0fd7d68bb97617fbd8 Mon Sep 17 00:00:00 2001 From: miseminger Date: Wed, 18 Sep 2024 02:11:09 -0700 Subject: [PATCH 034/161] Add RdRp back in to alias list --- assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json b/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json index 0c41208a..3fa7fbf2 100644 --- a/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json +++ b/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json @@ -13,7 +13,7 @@ "surface glycoprotein" : [], "3C-like proteinase" : ["3CL"], "leader protein" : ["nsp1"], - "RNA-dependent RNA polymerase" : ["nsp12"], + "RNA-dependent RNA polymerase" : ["RdRp", "nsp12"], "helicase" : ["nsp13"], "3'-to-5' exonuclease" : ["nsp14"], "2'-O-ribose methyltransferase" : ["nsp16"], From 220dc0846858467f344e971aa07b9624ff314699 Mon Sep 17 00:00:00 2001 From: miseminger Date: Wed, 18 Sep 2024 02:11:41 -0700 Subject: [PATCH 035/161] Add protein_alias lists manually --- .../NC_045512.2/NC_045512.2.json | 56 +++++++++---------- 1 file changed, 28 insertions(+), 28 deletions(-) diff --git a/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json b/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json index e843ec26..9c89c9ec 100644 --- a/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json +++ b/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json @@ -63,7 +63,7 @@ "aa_start": 1, "aa_end": 4400, "color": "rgb(217, 173, 61)", - "protein_alias": "ORF1a", + "protein_alias": ["ORF1a"], "protein_name": { "label": "open reading frame 1a polyprotein (SARS-CoV-2)", "uri": "GENEPIO:0101140" @@ -91,7 +91,7 @@ "aa_start": 1, "aa_end": 2695, "color": "rgb(80, 151, 186)", - "protein_alias": "ORF1b", + "protein_alias": ["ORF1b", "ORF1ab"], "protein_name": { "label": "open reading frame 1a polyprotein (SARS-CoV-2)", "uri": "GENEPIO:0101140" @@ -114,7 +114,7 @@ "aa_start": 1, "aa_end": 180, "color": "rgb(128,0,128)", - "protein_alias": "nsp1" + "protein_alias": ["nsp1"] }, "nsp2": { "type": "mature_protein_region_of_CDS", @@ -129,7 +129,7 @@ "aa_start": 181, "aa_end": 818, "color": "rgb(128,0,128)", - "protein_alias": "nsp2" + "protein_alias": ["nsp2"] }, "PL_pro": { "type": "mature_protein_region_of_CDS", @@ -144,7 +144,7 @@ "aa_start": 819, "aa_end": 2763, "color": "rgb(128,0,128)", - "protein_alias": "PL_pro" + "protein_alias": ["PL_pro", "PLpro"] }, "nsp4": { "type": "mature_protein_region_of_CDS", @@ -159,7 +159,7 @@ "aa_start": 2764, "aa_end": 3263, "color": "rgb(128,0,128)", - "protein_alias": "nsp4" + "protein_alias": ["nsp4"] }, "3CL": { "type": "mature_protein_region_of_CDS", @@ -174,7 +174,7 @@ "aa_start": 3264, "aa_end": 3569, "color": "rgb(128,0,128)", - "protein_alias": "3CL" + "protein_alias": ["3CL"] }, "nsp6": { "type": "mature_protein_region_of_CDS", @@ -189,7 +189,7 @@ "aa_start": 3570, "aa_end": 3859, "color": "rgb(128,0,128)", - "protein_alias": "nsp6" + "protein_alias": ["nsp6"] }, "nsp7": { "type": "mature_protein_region_of_CDS", @@ -204,7 +204,7 @@ "aa_start": 3860, "aa_end": 3942, "color": "rgb(128,0,128)", - "protein_alias": "nsp7" + "protein_alias": ["nsp7"] }, "nsp8": { "type": "mature_protein_region_of_CDS", @@ -219,7 +219,7 @@ "aa_start": 3943, "aa_end": 4140, "color": "rgb(128,0,128)", - "protein_alias": "nsp8" + "protein_alias": ["nsp8"] }, "nsp9": { "type": "mature_protein_region_of_CDS", @@ -234,7 +234,7 @@ "aa_start": 4141, "aa_end": 4253, "color": "rgb(128,0,128)", - "protein_alias": "nsp9" + "protein_alias": ["nsp9"] }, "nsp10": { "type": "mature_protein_region_of_CDS", @@ -249,7 +249,7 @@ "aa_start": 4254, "aa_end": 4392, "color": "rgb(128,0,128)", - "protein_alias": "nsp10" + "protein_alias": ["nsp10"] }, "RdRp": { "type": "mature_protein_region_of_CDS", @@ -264,7 +264,7 @@ "aa_start": 4393, "aa_end": 5324, "color": "rgb(128,0,128)", - "protein_alias": "RdRp" + "protein_alias": ["RdRp", "nsp12"] }, "nsp13": { "type": "mature_protein_region_of_CDS", @@ -279,7 +279,7 @@ "aa_start": 5325, "aa_end": 5925, "color": "rgb(128,0,128)", - "protein_alias": "nsp13" + "protein_alias": ["nsp13"] }, "nsp14": { "type": "mature_protein_region_of_CDS", @@ -294,7 +294,7 @@ "aa_start": 5926, "aa_end": 6452, "color": "rgb(128,0,128)", - "protein_alias": "nsp14" + "protein_alias": ["nsp14"] }, "nsp15": { "type": "mature_protein_region_of_CDS", @@ -309,7 +309,7 @@ "aa_start": 6453, "aa_end": 6798, "color": "rgb(128,0,128)", - "protein_alias": "nsp15" + "protein_alias": ["nsp15"] }, "nsp16": { "type": "mature_protein_region_of_CDS", @@ -324,7 +324,7 @@ "aa_start": 6799, "aa_end": 7096, "color": "rgb(128,0,128)", - "protein_alias": "nsp16" + "protein_alias": ["nsp16"] }, "nsp11": { "type": "mature_protein_region_of_CDS", @@ -339,7 +339,7 @@ "aa_start": 4393, "aa_end": 4405, "color": "rgb(128,0,128)", - "protein_alias": "nsp11" + "protein_alias": ["nsp11"] }, "stem_loop": { "type": "stem_loop", @@ -390,7 +390,7 @@ "aa_start": 1, "aa_end": 1273, "color": "rgb(142, 188, 102)", - "protein_alias": "S", + "protein_alias": [], "protein_name": { "label": "surface glycoprotein (SARS-CoV-2)", "uri": "GENEPIO:0101144" @@ -436,7 +436,7 @@ "aa_start": 1, "aa_end": 275, "color": "rgb(229, 150, 55)", - "protein_alias": "ORF3a", + "protein_alias": [], "protein_name": { "label": "open reading frame 3a protein (SARS-CoV-2)", "uri": "GENEPIO:0101148" @@ -483,7 +483,7 @@ "aa_start": 1, "aa_end": 75, "color": "rgb(170, 189, 82)", - "protein_alias": "E", + "protein_alias": [], "protein_name": { "label": "envelope protein (SARS-CoV-2)", "uri": "GENEPIO:0101152" @@ -530,7 +530,7 @@ "aa_start": 1, "aa_end": 222, "color": "rgb(223, 67, 39)", - "protein_alias": "M", + "protein_alias": [], "protein_name": { "label": "membrane glycoprotein (SARS-CoV-2)", "uri": "GENEPIO:0101156" @@ -576,7 +576,7 @@ "aa_start": 1, "aa_end": 61, "color": "rgb(196, 185, 69)", - "protein_alias": "ORF6", + "protein_alias": [], "protein_name": { "label": "open reading frame 6 protein (SARS-CoV-2)", "uri": "GENEPIO:0101160" @@ -622,7 +622,7 @@ "aa_start": 1, "aa_end": 121, "color": "rgb(117, 182, 129)", - "protein_alias": "ORF7a", + "protein_alias": [], "protein_name": { "label": "open reading frame 7a protein (SARS-CoV-2)", "uri": "GENEPIO:0101164" @@ -668,7 +668,7 @@ "aa_start": 1, "aa_end": 43, "color": "rgb(96, 170, 158)", - "protein_alias": "ORF7b", + "protein_alias": [], "protein_name": { "label": "open reading frame 7b protein (SARS-CoV-2)", "uri": "GENEPIO:0101168" @@ -714,7 +714,7 @@ "aa_start": 1, "aa_end": 121, "color": "rgb(217, 173, 61)", - "protein_alias": "ORF8", + "protein_alias": [], "protein_name": { "label": "open reading frame 8 protein (SARS-CoV-2)", "uri": "GENEPIO:0101172" @@ -761,7 +761,7 @@ "aa_start": 1, "aa_end": 419, "color": "rgb(80, 151, 186)", - "protein_alias": "N", + "protein_alias": [], "protein_name": { "label": "nucleocapsid phosphoprotein (SARS-CoV-2)", "uri": "GENEPIO:0101176" @@ -807,7 +807,7 @@ "aa_start": 1, "aa_end": 38, "color": "rgb(230, 112, 48)", - "protein_alias": "ORF10", + "protein_alias": [], "protein_name": { "label": "open reading frame 10 protein (SARS-CoV-2)", "uri": "GENEPIO:0101180" From c55d674429e5a4c208f5a0c523a0a043f63a8a0d Mon Sep 17 00:00:00 2001 From: miseminger Date: Wed, 18 Sep 2024 04:35:27 -0700 Subject: [PATCH 036/161] Add ontology terms to functional annotation file --- bin/functional_annotation.py | 90 +++++++++++++++++++++++++++++++----- 1 file changed, 78 insertions(+), 12 deletions(-) diff --git a/bin/functional_annotation.py b/bin/functional_annotation.py index 465d87a3..5eab3889 100755 --- a/bin/functional_annotation.py +++ b/bin/functional_annotation.py @@ -31,6 +31,9 @@ def parse_args(): help='versioned reference accession from RefSeq') parser.add_argument('--mutation_index', type=str, default='n/a', help='index of all mutations (.TSV)') + parser.add_argument('--gene_positions', type=str, + default=None, required=True, + help='gene positions in JSON format') parser.add_argument('--outputfile', type=str, required=True, help='output file (.TSV) format') parser.add_argument('--save_dois', type=str, default=None, @@ -152,12 +155,12 @@ def extract_metadata(inp_file, chunk, df): function_category] #, comb_mutation, heterozygosity] # print(df_list) df1 = pd.DataFrame( - columns=['original mutation description', 'protein symbol', 'variant functional effect']) + columns=['original mutation description', 'pokay_id', 'variant functional effect']) #'comb_mutation', 'heterozygosity']) df1.loc[len(df1)] = df_list df_func['original mutation description'] = df1['original mutation description'].iloc[0] - df_func['protein symbol'] = df1['protein symbol'].iloc[0] + df_func['pokay_id'] = df1['pokay_id'].iloc[0] df_func['variant functional effect'] = df1['variant functional effect'].iloc[0] #df_func['comb_mutation'] = str(df1['comb_mutation'].iloc[0]) #df_func['heterozygosity'] = str(df1['heterozygosity'].iloc[0]) @@ -246,31 +249,94 @@ def write_tsv(dframe): dataFrame.loc[dataFrame['peer review status'].str.contains("Preprint"), 'peer review status'] = 'false' dataFrame.loc[dataFrame['peer review status'].str.contains("Grey literature"), 'peer review status'] = 'false' ##up for debate - # before merging, unnest the 'original mutation description' column + # map 'pokay_id' to 'protein_symbol' and 'mat_pep' based on JSON + pokay_id_set = set(dataFrame['pokay_id'].tolist()) + print(pokay_id_set) + #pokay_id_set = {'RdRp', 'nsp4', 'M', 'ORF8', '3CL', 'nsp1', 'E', 'S', 'nsp8', 'ORF6', 'N', 'PLpro', 'nsp7', 'ORF3a', 'nsp9', 'nsp6', 'nsp2'} + dataFrame['gene name'] = '' + dataFrame['gene symbol'] = '' + dataFrame['protein name'] = '' + dataFrame['protein symbol'] = '' + dataFrame['mat_pep'] = '' + + # Reading the gene & protein coordinates of SARS-CoV-2 genome + with open(args.gene_positions) as fp: + + GENE_PROTEIN_POSITIONS_DICT = json.load(fp) + + for pokay_id in pokay_id_set: + for entry in GENE_PROTEIN_POSITIONS_DICT.keys(): + + # If a gene record matches pokay_id, get 'gene_name' and 'gene_symbol' + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="gene" and GENE_PROTEIN_POSITIONS_DICT[entry]["gene"]==pokay_id: + # extract protein names and symbols (ontology) from JSON entry + gene_name = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_name"]["label"] + gene_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_symbol"]["label"] + # add gene names and symbols to dataframe + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene name"] = gene_name + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene symbol"] = gene_symbol + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene"] = GENE_PROTEIN_POSITIONS_DICT[entry]["gene"] + + # If a CDS record matches pokay_id, get 'protein_name' and 'protein_symbol' + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="CDS" and GENE_PROTEIN_POSITIONS_DICT[entry]["gene"]==pokay_id: + # extract protein names and symbols (ontology) from JSON entry + protein_name = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_name"]["label"] + protein_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_symbol"]["label"] + # add protein names and symbols to dataframe + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "protein name"] = protein_name + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "protein symbol"] = protein_symbol + + # If a mature peptide record matches pokay_id in the 'protein_alias' list, get name of parent, and from there get names and symbols + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="mature_protein_region_of_CDS" and (pokay_id in GENE_PROTEIN_POSITIONS_DICT[entry]["protein_alias"]): + # extract pokay_id, mat_pep, and parent id from JSON entry + mat_pep = entry + parent = GENE_PROTEIN_POSITIONS_DICT[entry]["Parent"] + # get parent protein name and symbol from corresponding CDS entry, matching "Parent" to "ID" + for entry in GENE_PROTEIN_POSITIONS_DICT.keys(): + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="CDS" and (GENE_PROTEIN_POSITIONS_DICT[entry]["ID"]==parent): + parent_protein_name = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_name"]["label"] + parent_protein_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_symbol"]["label"] + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "protein name"] = parent_protein_name + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "protein symbol"] = parent_protein_symbol + parent_gene = GENE_PROTEIN_POSITIONS_DICT[entry]["gene"] + # get parent gene name and symbol from corresponding parent gene entry + for entry in GENE_PROTEIN_POSITIONS_DICT.keys(): + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="gene" and (GENE_PROTEIN_POSITIONS_DICT[entry]["gene"]==parent_gene): + # extract gene names and symbols (ontology) from JSON entry + parent_gene_name = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_name"]["label"] + parent_gene_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_symbol"]["label"] + # add gene names and symbols to dataframe + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene name"] = parent_gene_name + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene symbol"] = parent_gene_symbol + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene"] = GENE_PROTEIN_POSITIONS_DICT[entry]["gene"] + # fill in mat_pep + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "mat_pep"] = mat_pep + + #dataFrame[['pokay_id', 'gene name', 'gene symbol', 'protein name', 'protein symbol', 'mat_pep', 'gene']].drop_duplicates().to_csv('../test_data/pokay_id.tsv', sep='\t', index=False) + #print("saved as '../test_data/pokay_id.tsv'") + + #before merging, unnest the 'original mutation description' column dataFrame["original mutation description"] = dataFrame["original mutation description"].str.split(',') dataFrame = unnest_multi(dataFrame, ["original mutation description"], reset_index=False) dataFrame['index1'] = dataFrame.index - # if mutation index: add HGVS mutations names, nucleotide positions, protein names, protein symbols, and gene names from it + # if mutation index: add HGVS mutations names, nucleotide positions from it if args.mutation_index != 'n/a': mutation_index = pd.read_csv(args.mutation_index, sep='\t') # merge on "mutation" and "protein symbol" in index ("original mutation description" and "protein symbol" in functional annotation file) mutation_index = mutation_index.rename(columns={"mutation": "original mutation description", 'pos':'nucleotide position', 'hgvs_aa_mutation':'amino acid mutation','hgvs_nt_mutation':'nucleotide mutation', - 'gene_name':'gene name', 'gene_symbol':'gene symbol', 'protein_name':'protein name', - 'protein_symbol':'protein symbol', 'hgvs_alias':'amino acid mutation alias'}) + 'hgvs_alias':'amino acid mutation alias', 'gene_symbol':'gene'}) + print("columns", mutation_index.columns) # remove doubled columns from dataFrame - index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', - 'protein name', 'gene symbol', 'gene name'] + index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias'] dataFrame = dataFrame.drop(columns=index_cols_to_use) - print('pokay', set(dataFrame['protein symbol'].tolist())) - print('index', set(mutation_index['protein symbol'].tolist())) - merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'protein symbol'], how='left') #, 'alias' + merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'gene', 'mat_pep'], how='left') #dups = mutation_index[mutation_index.duplicated(subset=['nucleotide position', 'original mutation description'], keep=False)] #dups = dups.sort_values(by='nucleotide position') #dups.to_csv('madeline_testing/dups.tsv', sep='\t', index=False) - # keep only specified columns + # keep only specified columns, discarding 'pokay_id' here merged_dataFrame = merged_dataFrame[['index1'] + dataFrame_cols] # drop mutations not found in the index From 5f8cc07c6a22cb73872c6a945db07b5ae0941944 Mon Sep 17 00:00:00 2001 From: miseminger Date: Wed, 18 Sep 2024 04:46:34 -0700 Subject: [PATCH 037/161] Update column names to match template --- bin/functional_annotation.py | 26 +++++++++++++------------- 1 file changed, 13 insertions(+), 13 deletions(-) diff --git a/bin/functional_annotation.py b/bin/functional_annotation.py index 5eab3889..09e56ac3 100755 --- a/bin/functional_annotation.py +++ b/bin/functional_annotation.py @@ -50,16 +50,16 @@ def combination_mutation(c_mutations, c_mutation): def data_cleanup(dframe): - dframe['variant functional effect description'] = dframe[ - 'variant functional effect description'].apply( + dframe['measured variant functional effect description'] = dframe[ + 'measured variant functional effect description'].apply( lambda x: ','.join(map(str, x))) - dframe['variant functional effect description'] = dframe[ - 'variant functional effect description'].str.replace(',#', '') - dframe['variant functional effect description'] = dframe[ - 'variant functional effect description'].str.replace('#', '') - dframe['variant functional effect description'] = dframe[ - 'variant functional effect description'].str.strip() + dframe['measured variant functional effect description'] = dframe[ + 'measured variant functional effect description'].str.replace(',#', '') + dframe['measured variant functional effect description'] = dframe[ + 'measured variant functional effect description'].str.replace('#', '') + dframe['measured variant functional effect description'] = dframe[ + 'measured variant functional effect description'].str.strip() #dframe['comb_mutation'] = dframe['comb_mutation'].apply( # lambda x: x[1:-1]) @@ -149,19 +149,19 @@ def extract_metadata(inp_file, chunk, df): del function[chunk[url[index_url - 1]]] df_func = pd.DataFrame(function.items(), columns=['url', - 'variant functional effect description']) + 'measured variant functional effect description']) df_list = [mutation_name, gene_name, function_category] #, comb_mutation, heterozygosity] # print(df_list) df1 = pd.DataFrame( - columns=['original mutation description', 'pokay_id', 'variant functional effect']) + columns=['original mutation description', 'pokay_id', 'measured variant functional effect']) #'comb_mutation', 'heterozygosity']) df1.loc[len(df1)] = df_list df_func['original mutation description'] = df1['original mutation description'].iloc[0] df_func['pokay_id'] = df1['pokay_id'].iloc[0] - df_func['variant functional effect'] = df1['variant functional effect'].iloc[0] + df_func['measured variant functional effect'] = df1['measured variant functional effect'].iloc[0] #df_func['comb_mutation'] = str(df1['comb_mutation'].iloc[0]) #df_func['heterozygosity'] = str(df1['heterozygosity'].iloc[0]) @@ -190,8 +190,8 @@ def write_tsv(dframe): dataFrame_cols = ['organism', 'reference accession', 'reference database name', 'nucleotide position', 'original mutation description', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', -'gene name', 'gene symbol', 'protein name', 'protein symbol', 'variant functional effect', -'variant functional effect description', 'author', 'publication year', 'URL', 'DOI', 'PMID', +'gene name', 'gene symbol', 'protein name', 'protein symbol', 'measured variant functional effect', 'inferred variant functional effect', 'viral life cycle functional effect', +'measured variant functional effect description', 'CVX code', 'DrugBank Accession Number', 'Antibody Registry ID', 'author', 'publication year', 'URL', 'DOI', 'PMID', 'peer review status', 'curator', 'mutation functional annotation resource'] dataFrame = pd.DataFrame(columns=dataFrame_cols) From fc78ab04beede75f9dbde9aa750239f751ed039a Mon Sep 17 00:00:00 2001 From: miseminger Date: Wed, 18 Sep 2024 12:43:20 -0700 Subject: [PATCH 038/161] Don't merge on mat_pep anymore --- bin/functional_annotation.py | 7 +++---- 1 file changed, 3 insertions(+), 4 deletions(-) diff --git a/bin/functional_annotation.py b/bin/functional_annotation.py index 09e56ac3..062585ef 100755 --- a/bin/functional_annotation.py +++ b/bin/functional_annotation.py @@ -251,7 +251,6 @@ def write_tsv(dframe): # map 'pokay_id' to 'protein_symbol' and 'mat_pep' based on JSON pokay_id_set = set(dataFrame['pokay_id'].tolist()) - print(pokay_id_set) #pokay_id_set = {'RdRp', 'nsp4', 'M', 'ORF8', '3CL', 'nsp1', 'E', 'S', 'nsp8', 'ORF6', 'N', 'PLpro', 'nsp7', 'ORF3a', 'nsp9', 'nsp6', 'nsp2'} dataFrame['gene name'] = '' dataFrame['gene symbol'] = '' @@ -312,8 +311,8 @@ def write_tsv(dframe): # fill in mat_pep dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "mat_pep"] = mat_pep - #dataFrame[['pokay_id', 'gene name', 'gene symbol', 'protein name', 'protein symbol', 'mat_pep', 'gene']].drop_duplicates().to_csv('../test_data/pokay_id.tsv', sep='\t', index=False) - #print("saved as '../test_data/pokay_id.tsv'") +# dataFrame[['pokay_id', 'gene name', 'gene symbol', 'protein name', 'protein symbol', 'mat_pep', 'gene']].drop_duplicates().to_csv('../test_data/pokay_id.tsv', sep='|', index=False) +# print("saved as '../test_data/pokay_id.tsv'") #before merging, unnest the 'original mutation description' column dataFrame["original mutation description"] = dataFrame["original mutation description"].str.split(',') @@ -331,7 +330,7 @@ def write_tsv(dframe): # remove doubled columns from dataFrame index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias'] dataFrame = dataFrame.drop(columns=index_cols_to_use) - merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'gene', 'mat_pep'], how='left') + merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'gene'], how='left') #, 'mat_pep' #dups = mutation_index[mutation_index.duplicated(subset=['nucleotide position', 'original mutation description'], keep=False)] #dups = dups.sort_values(by='nucleotide position') #dups.to_csv('madeline_testing/dups.tsv', sep='\t', index=False) From e0896c86e926e3be8dbf425a79143b5439a63b09 Mon Sep 17 00:00:00 2001 From: miseminger Date: Wed, 18 Sep 2024 12:45:17 -0700 Subject: [PATCH 039/161] add BioRegistry prefix for doi --- bin/functional_annotation.py | 3 +++ 1 file changed, 3 insertions(+) diff --git a/bin/functional_annotation.py b/bin/functional_annotation.py index 062585ef..c5eb494d 100755 --- a/bin/functional_annotation.py +++ b/bin/functional_annotation.py @@ -240,6 +240,9 @@ def write_tsv(dframe): dataFrame["DOI"] = dataFrame["DOI"].str.strip() dataFrame["URL"] = dataFrame["URL"].str.strip() + # add BioRegistry prefix for doi + dataFrame["DOI"] = "doi:" + dataFrame["DOI"] + # add temporary curator name dataFrame["curator"] = "Paul Gordon" ## for now: need to go through From 668c0dc007778607f0499847d1e079cda6155b89 Mon Sep 17 00:00:00 2001 From: miseminger Date: Wed, 18 Sep 2024 23:42:17 -0700 Subject: [PATCH 040/161] Add MPOX ROBOT table --- .../NC_063383.1/NC_063383.1_ROBOT.tsv | 705 ++++++++++++++++++ 1 file changed, 705 insertions(+) create mode 100644 assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ROBOT.tsv diff --git a/assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ROBOT.tsv b/assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ROBOT.tsv new file mode 100644 index 00000000..8fd8ad53 --- /dev/null +++ b/assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ROBOT.tsv @@ -0,0 +1,705 @@ +Issues / Notes Ontology ID parent class Equivalence axiom Subclass axiom label definition references definition source alternative label Reported term tracker item entity type created parent class ID is about label alt definition is about comment example of usage contributor curation status editor note database cross reference see also Subclass ID Subclass label english exact synonym english broad synonym english narrow synonym english related synonym Dbxref + GENEPIO:0101207 gene name (MPOX) orthopoxvirus gene 001 (MPOX) A gene name that denotes the opg001 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551607 + GENEPIO:0101207 gene name (MPOX) orthopoxvirus gene 001 (MPOX) A gene name that denotes the opg001 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551595 + GENEPIO:0101208 gene name (MPOX) orthopoxvirus gene 002 (MPOX) A gene name that denotes the opg002 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551418 + GENEPIO:0101208 gene name (MPOX) orthopoxvirus gene 002 (MPOX) A gene name that denotes the opg002 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551594 + GENEPIO:0101209 gene name (MPOX) orthopoxvirus gene 003 (MPOX) A gene name that denotes the opg003 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551419 + GENEPIO:0101209 gene name (MPOX) orthopoxvirus gene 003 (MPOX) A gene name that denotes the opg003 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551593 + GENEPIO:0101210 gene name (MPOX) orthopoxvirus gene 015 (MPOX) A gene name that denotes the opg015 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551420 + GENEPIO:0101210 gene name (MPOX) orthopoxvirus gene 015 (MPOX) A gene name that denotes the opg015 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551592 + GENEPIO:0101211 gene name (MPOX) orthopoxvirus gene 019 (MPOX) A gene name that denotes the opg019 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551421 + GENEPIO:0101212 gene name (MPOX) orthopoxvirus gene 021 (MPOX) A gene name that denotes the opg021 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551422 + GENEPIO:0101213 gene name (MPOX) orthopoxvirus gene 022 (MPOX) A gene name that denotes the opg022 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551423 + GENEPIO:0101214 gene name (MPOX) orthopoxvirus gene 023 (MPOX) A gene name that denotes the opg023 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551424 + GENEPIO:0101215 gene name (MPOX) orthopoxvirus gene 024 (MPOX) A gene name that denotes the opg024 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551425 + GENEPIO:0101216 gene name (MPOX) orthopoxvirus gene 025 (MPOX) A gene name that denotes the opg025 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551426 + GENEPIO:0101217 gene name (MPOX) orthopoxvirus gene 027 (MPOX) A gene name that denotes the opg027 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551427 + GENEPIO:0101218 gene name (MPOX) orthopoxvirus gene 029 (MPOX) A gene name that denotes the opg029 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551428 + GENEPIO:0101219 gene name (MPOX) orthopoxvirus gene 030 (MPOX) A gene name that denotes the opg030 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551429 + GENEPIO:0101220 gene name (MPOX) orthopoxvirus gene 031 (MPOX) A gene name that denotes the opg031 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551430 + GENEPIO:0101221 gene name (MPOX) orthopoxvirus gene 034 (MPOX) A gene name that denotes the opg034 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551431 + GENEPIO:0101222 gene name (MPOX) orthopoxvirus gene 035 (MPOX) A gene name that denotes the opg035 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551432 + GENEPIO:0101224 gene name (MPOX) orthopoxvirus gene 037 (MPOX) A gene name that denotes the opg037 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551434 + GENEPIO:0101225 gene name (MPOX) orthopoxvirus gene 038 (MPOX) A gene name that denotes the opg038 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551435 + GENEPIO:0101226 gene name (MPOX) orthopoxvirus gene 039 (MPOX) A gene name that denotes the opg039 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551436 + GENEPIO:0101227 gene name (MPOX) orthopoxvirus gene 040 (MPOX) A gene name that denotes the opg040 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551437 + GENEPIO:0101228 gene name (MPOX) orthopoxvirus gene 042 (MPOX) A gene name that denotes the opg042 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551438 + GENEPIO:0101229 gene name (MPOX) orthopoxvirus gene 043 (MPOX) A gene name that denotes the opg043 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551439 + GENEPIO:0101231 gene name (MPOX) orthopoxvirus gene 045 (MPOX) A gene name that denotes the opg045 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551441 + GENEPIO:0101232 gene name (MPOX) orthopoxvirus gene 046 (MPOX) A gene name that denotes the opg046 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551442 + GENEPIO:0101233 gene name (MPOX) orthopoxvirus gene 047 (MPOX) A gene name that denotes the opg047 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551443 + GENEPIO:0101234 gene name (MPOX) orthopoxvirus gene 048 (MPOX) A gene name that denotes the opg048 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551444 + GENEPIO:0101235 gene name (MPOX) orthopoxvirus gene 049 (MPOX) A gene name that denotes the opg049 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551445 + GENEPIO:0101236 gene name (MPOX) orthopoxvirus gene 050 (MPOX) A gene name that denotes the opg050 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551446 + GENEPIO:0101237 gene name (MPOX) orthopoxvirus gene 051 (MPOX) A gene name that denotes the opg051 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551447 + GENEPIO:0101238 gene name (MPOX) orthopoxvirus gene 052 (MPOX) A gene name that denotes the opg052 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551448 + GENEPIO:0101239 gene name (MPOX) orthopoxvirus gene 053 (MPOX) A gene name that denotes the opg053 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551449 + GENEPIO:0101240 gene name (MPOX) orthopoxvirus gene 054 (MPOX) A gene name that denotes the opg054 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551450 + GENEPIO:0101241 gene name (MPOX) orthopoxvirus gene 055 (MPOX) A gene name that denotes the opg055 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551451 + GENEPIO:0101242 gene name (MPOX) orthopoxvirus gene 056 (MPOX) A gene name that denotes the opg056 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551452 + GENEPIO:0101243 gene name (MPOX) orthopoxvirus gene 057 (MPOX) A gene name that denotes the opg057 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551453 + GENEPIO:0101244 gene name (MPOX) orthopoxvirus gene 058 (MPOX) A gene name that denotes the opg058 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551454 + GENEPIO:0101245 gene name (MPOX) orthopoxvirus gene 059 (MPOX) A gene name that denotes the opg059 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551455 + GENEPIO:0101246 gene name (MPOX) orthopoxvirus gene 060 (MPOX) A gene name that denotes the opg060 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551456 + GENEPIO:0101247 gene name (MPOX) orthopoxvirus gene 061 (MPOX) A gene name that denotes the opg061 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551457 + GENEPIO:0101248 gene name (MPOX) orthopoxvirus gene 062 (MPOX) A gene name that denotes the opg062 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551458 + GENEPIO:0101249 gene name (MPOX) orthopoxvirus gene 063 (MPOX) A gene name that denotes the opg063 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551459 + GENEPIO:0101250 gene name (MPOX) orthopoxvirus gene 064 (MPOX) A gene name that denotes the opg064 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551460 + GENEPIO:0101251 gene name (MPOX) orthopoxvirus gene 065 (MPOX) A gene name that denotes the opg065 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551461 + GENEPIO:0101252 gene name (MPOX) orthopoxvirus gene 066 (MPOX) A gene name that denotes the opg066 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551462 + GENEPIO:0101253 gene name (MPOX) orthopoxvirus gene 068 (MPOX) A gene name that denotes the opg068 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551463 + GENEPIO:0101254 gene name (MPOX) orthopoxvirus gene 069 (MPOX) A gene name that denotes the opg069 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551464 + GENEPIO:0101255 gene name (MPOX) orthopoxvirus gene 070 (MPOX) A gene name that denotes the opg070 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551465 + GENEPIO:0101256 gene name (MPOX) orthopoxvirus gene 071 (MPOX) A gene name that denotes the opg071 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551466 + GENEPIO:0101257 gene name (MPOX) orthopoxvirus gene 072 (MPOX) A gene name that denotes the opg072 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551467 + GENEPIO:0101258 gene name (MPOX) orthopoxvirus gene 073 (MPOX) A gene name that denotes the opg073 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551468 + GENEPIO:0101259 gene name (MPOX) orthopoxvirus gene 074 (MPOX) A gene name that denotes the opg074 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551469 + GENEPIO:0101260 gene name (MPOX) orthopoxvirus gene 075 (MPOX) A gene name that denotes the opg075 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551470 + GENEPIO:0101262 gene name (MPOX) orthopoxvirus gene 077 (MPOX) A gene name that denotes the opg077 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551472 + GENEPIO:0101263 gene name (MPOX) orthopoxvirus gene 078 (MPOX) A gene name that denotes the opg078 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551473 + GENEPIO:0101264 gene name (MPOX) orthopoxvirus gene 079 (MPOX) A gene name that denotes the opg079 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551474 + GENEPIO:0101265 gene name (MPOX) orthopoxvirus gene 080 (MPOX) A gene name that denotes the opg080 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551475 + GENEPIO:0101266 gene name (MPOX) orthopoxvirus gene 081 (MPOX) A gene name that denotes the opg081 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551476 + GENEPIO:0101267 gene name (MPOX) orthopoxvirus gene 082 (MPOX) A gene name that denotes the opg082 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551477 + GENEPIO:0101268 gene name (MPOX) orthopoxvirus gene 083 (MPOX) A gene name that denotes the opg083 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551478 + GENEPIO:0101269 gene name (MPOX) orthopoxvirus gene 084 (MPOX) A gene name that denotes the opg084 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551479 + GENEPIO:0101270 gene name (MPOX) orthopoxvirus gene 085 (MPOX) A gene name that denotes the opg085 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551480 + GENEPIO:0101271 gene name (MPOX) orthopoxvirus gene 086 (MPOX) A gene name that denotes the opg086 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551481 + GENEPIO:0101272 gene name (MPOX) orthopoxvirus gene 087 (MPOX) A gene name that denotes the opg087 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551482 + GENEPIO:0101273 gene name (MPOX) orthopoxvirus gene 088 (MPOX) A gene name that denotes the opg088 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551483 + GENEPIO:0101274 gene name (MPOX) orthopoxvirus gene 089 (MPOX) A gene name that denotes the opg089 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551484 + GENEPIO:0101275 gene name (MPOX) orthopoxvirus gene 090 (MPOX) A gene name that denotes the opg090 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551485 + GENEPIO:0101276 gene name (MPOX) orthopoxvirus gene 091 (MPOX) A gene name that denotes the opg091 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551486 + GENEPIO:0101277 gene name (MPOX) orthopoxvirus gene 092 (MPOX) A gene name that denotes the opg092 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551487 + GENEPIO:0101278 gene name (MPOX) orthopoxvirus gene 093 (MPOX) A gene name that denotes the opg093 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551488 + GENEPIO:0101279 gene name (MPOX) orthopoxvirus gene 094 (MPOX) A gene name that denotes the opg094 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551489 + GENEPIO:0101280 gene name (MPOX) orthopoxvirus gene 095 (MPOX) A gene name that denotes the opg095 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551490 + GENEPIO:0101281 gene name (MPOX) orthopoxvirus gene 096 (MPOX) A gene name that denotes the opg096 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551491 + GENEPIO:0101282 gene name (MPOX) orthopoxvirus gene 097 (MPOX) A gene name that denotes the opg097 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551492 + GENEPIO:0101283 gene name (MPOX) orthopoxvirus gene 098 (MPOX) A gene name that denotes the opg098 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551493 + GENEPIO:0101284 gene name (MPOX) orthopoxvirus gene 099 (MPOX) A gene name that denotes the opg099 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551494 + GENEPIO:0101285 gene name (MPOX) orthopoxvirus gene 100 (MPOX) A gene name that denotes the opg100 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551495 + GENEPIO:0101286 gene name (MPOX) orthopoxvirus gene 101 (MPOX) A gene name that denotes the opg101 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551496 + GENEPIO:0101287 gene name (MPOX) orthopoxvirus gene 102 (MPOX) A gene name that denotes the opg102 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551497 + GENEPIO:0101288 gene name (MPOX) orthopoxvirus gene 103 (MPOX) A gene name that denotes the opg103 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551498 + GENEPIO:0101289 gene name (MPOX) orthopoxvirus gene 104 (MPOX) A gene name that denotes the opg104 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551499 + GENEPIO:0101290 gene name (MPOX) orthopoxvirus gene 105 (MPOX) A gene name that denotes the opg105 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551500 + GENEPIO:0101291 gene name (MPOX) orthopoxvirus gene 106 (MPOX) A gene name that denotes the opg106 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551501 + GENEPIO:0101292 gene name (MPOX) orthopoxvirus gene 107 (MPOX) A gene name that denotes the opg107 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551502 + GENEPIO:0101293 gene name (MPOX) orthopoxvirus gene 108 (MPOX) A gene name that denotes the opg108 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551503 + GENEPIO:0101294 gene name (MPOX) orthopoxvirus gene 109 (MPOX) A gene name that denotes the opg109 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551504 + GENEPIO:0101295 gene name (MPOX) orthopoxvirus gene 110 (MPOX) A gene name that denotes the opg110 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551505 + GENEPIO:0101296 gene name (MPOX) orthopoxvirus gene 111 (MPOX) A gene name that denotes the opg111 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551506 + GENEPIO:0101297 gene name (MPOX) orthopoxvirus gene 112 (MPOX) A gene name that denotes the opg112 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551507 + GENEPIO:0101298 gene name (MPOX) orthopoxvirus gene 113 (MPOX) A gene name that denotes the opg113 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551508 + GENEPIO:0101299 gene name (MPOX) orthopoxvirus gene 114 (MPOX) A gene name that denotes the opg114 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551509 + GENEPIO:0101300 gene name (MPOX) orthopoxvirus gene 115 (MPOX) A gene name that denotes the opg115 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551510 + GENEPIO:0101301 gene name (MPOX) orthopoxvirus gene 116 (MPOX) A gene name that denotes the opg116 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551511 + GENEPIO:0101302 gene name (MPOX) orthopoxvirus gene 117 (MPOX) A gene name that denotes the opg117 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551512 + GENEPIO:0101303 gene name (MPOX) orthopoxvirus gene 118 (MPOX) A gene name that denotes the opg118 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551513 + GENEPIO:0101304 gene name (MPOX) orthopoxvirus gene 119 (MPOX) A gene name that denotes the opg119 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551514 + GENEPIO:0101305 gene name (MPOX) orthopoxvirus gene 120 (MPOX) A gene name that denotes the opg120 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551515 + GENEPIO:0101306 gene name (MPOX) orthopoxvirus gene 121 (MPOX) A gene name that denotes the opg121 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551516 + GENEPIO:0101307 gene name (MPOX) orthopoxvirus gene 122 (MPOX) A gene name that denotes the opg122 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551517 + GENEPIO:0101308 gene name (MPOX) orthopoxvirus gene 123 (MPOX) A gene name that denotes the opg123 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551518 + GENEPIO:0101309 gene name (MPOX) orthopoxvirus gene 124 (MPOX) A gene name that denotes the opg124 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551519 + GENEPIO:0101310 gene name (MPOX) orthopoxvirus gene 125 (MPOX) A gene name that denotes the opg125 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551520 + GENEPIO:0101311 gene name (MPOX) orthopoxvirus gene 126 (MPOX) A gene name that denotes the opg126 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551521 + GENEPIO:0101312 gene name (MPOX) orthopoxvirus gene 127 (MPOX) A gene name that denotes the opg127 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551522 + GENEPIO:0101313 gene name (MPOX) orthopoxvirus gene 128 (MPOX) A gene name that denotes the opg128 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551523 + GENEPIO:0101314 gene name (MPOX) orthopoxvirus gene 129 (MPOX) A gene name that denotes the opg129 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551524 + GENEPIO:0101315 gene name (MPOX) orthopoxvirus gene 130 (MPOX) A gene name that denotes the opg130 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551525 + GENEPIO:0101316 gene name (MPOX) orthopoxvirus gene 131 (MPOX) A gene name that denotes the opg131 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551526 + GENEPIO:0101317 gene name (MPOX) orthopoxvirus gene 132 (MPOX) A gene name that denotes the opg132 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551527 + GENEPIO:0101318 gene name (MPOX) orthopoxvirus gene 133 (MPOX) A gene name that denotes the opg133 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551528 + GENEPIO:0101319 gene name (MPOX) orthopoxvirus gene 134 (MPOX) A gene name that denotes the opg134 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551529 + GENEPIO:0101320 gene name (MPOX) orthopoxvirus gene 135 (MPOX) A gene name that denotes the opg135 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551530 + GENEPIO:0101321 gene name (MPOX) orthopoxvirus gene 136 (MPOX) A gene name that denotes the opg136 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551531 + GENEPIO:0101322 gene name (MPOX) orthopoxvirus gene 137 (MPOX) A gene name that denotes the opg137 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551532 + GENEPIO:0101323 gene name (MPOX) orthopoxvirus gene 138 (MPOX) A gene name that denotes the opg138 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551533 + GENEPIO:0101324 gene name (MPOX) orthopoxvirus gene 139 (MPOX) A gene name that denotes the opg139 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551534 + GENEPIO:0101325 gene name (MPOX) orthopoxvirus gene 140 (MPOX) A gene name that denotes the opg140 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551535 + GENEPIO:0101326 gene name (MPOX) orthopoxvirus gene 141 (MPOX) A gene name that denotes the opg141 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551536 + GENEPIO:0101327 gene name (MPOX) orthopoxvirus gene 142 (MPOX) A gene name that denotes the opg142 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551537 + GENEPIO:0101328 gene name (MPOX) orthopoxvirus gene 143 (MPOX) A gene name that denotes the opg143 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551538 + GENEPIO:0101329 gene name (MPOX) orthopoxvirus gene 144 (MPOX) A gene name that denotes the opg144 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551539 + GENEPIO:0101330 gene name (MPOX) orthopoxvirus gene 145 (MPOX) A gene name that denotes the opg145 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551540 + GENEPIO:0101331 gene name (MPOX) orthopoxvirus gene 146 (MPOX) A gene name that denotes the opg146 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551541 + GENEPIO:0101332 gene name (MPOX) orthopoxvirus gene 147 (MPOX) A gene name that denotes the opg147 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551542 + GENEPIO:0101333 gene name (MPOX) orthopoxvirus gene 148 (MPOX) A gene name that denotes the opg148 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551543 + GENEPIO:0101334 gene name (MPOX) orthopoxvirus gene 149 (MPOX) A gene name that denotes the opg149 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551544 + GENEPIO:0101335 gene name (MPOX) orthopoxvirus gene 150 (MPOX) A gene name that denotes the opg150 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551545 + GENEPIO:0101336 gene name (MPOX) orthopoxvirus gene 151 (MPOX) A gene name that denotes the opg151 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551546 + GENEPIO:0101337 gene name (MPOX) orthopoxvirus gene 153 (MPOX) A gene name that denotes the opg153 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551547 + GENEPIO:0101338 gene name (MPOX) orthopoxvirus gene 154 (MPOX) A gene name that denotes the opg154 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551548 + GENEPIO:0101339 gene name (MPOX) orthopoxvirus gene 155 (MPOX) A gene name that denotes the opg155 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551549 + GENEPIO:0101340 gene name (MPOX) orthopoxvirus gene 156 (MPOX) A gene name that denotes the opg156 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551550 + GENEPIO:0101341 gene name (MPOX) orthopoxvirus gene 157 (MPOX) A gene name that denotes the opg157 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551551 + GENEPIO:0101342 gene name (MPOX) orthopoxvirus gene 158 (MPOX) A gene name that denotes the opg158 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551552 + GENEPIO:0101343 gene name (MPOX) orthopoxvirus gene 159 (MPOX) A gene name that denotes the opg159 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551553 + GENEPIO:0101344 gene name (MPOX) orthopoxvirus gene 160 (MPOX) A gene name that denotes the opg160 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551554 + GENEPIO:0101345 gene name (MPOX) orthopoxvirus gene 161 (MPOX) A gene name that denotes the opg161 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551555 + GENEPIO:0101346 gene name (MPOX) orthopoxvirus gene 162 (MPOX) A gene name that denotes the opg162 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551556 + GENEPIO:0101347 gene name (MPOX) orthopoxvirus gene 163 (MPOX) A gene name that denotes the opg163 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551557 + GENEPIO:0101348 gene name (MPOX) orthopoxvirus gene 164 (MPOX) A gene name that denotes the opg164 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551558 + GENEPIO:0101349 gene name (MPOX) orthopoxvirus gene 165 (MPOX) A gene name that denotes the opg165 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551559 + GENEPIO:0101350 gene name (MPOX) orthopoxvirus gene 166 (MPOX) A gene name that denotes the opg166 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551560 + GENEPIO:0101351 gene name (MPOX) orthopoxvirus gene 167 (MPOX) A gene name that denotes the opg167 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551561 + GENEPIO:0101352 gene name (MPOX) orthopoxvirus gene 170 (MPOX) A gene name that denotes the opg170 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551562 + GENEPIO:0101353 gene name (MPOX) orthopoxvirus gene 171 (MPOX) A gene name that denotes the opg171 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551563 + GENEPIO:0101354 gene name (MPOX) orthopoxvirus gene 172 (MPOX) A gene name that denotes the opg172 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551564 + GENEPIO:0101355 gene name (MPOX) orthopoxvirus gene 173 (MPOX) A gene name that denotes the opg173 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551565 + GENEPIO:0101356 gene name (MPOX) orthopoxvirus gene 174 (MPOX) A gene name that denotes the opg174 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551566 + GENEPIO:0101357 gene name (MPOX) orthopoxvirus gene 175 (MPOX) A gene name that denotes the opg175 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551567 + GENEPIO:0101358 gene name (MPOX) orthopoxvirus gene 176 (MPOX) A gene name that denotes the opg176 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551568 + GENEPIO:0101359 gene name (MPOX) orthopoxvirus gene 178 (MPOX) A gene name that denotes the opg178 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551569 + GENEPIO:0101360 gene name (MPOX) orthopoxvirus gene 180 (MPOX) A gene name that denotes the opg180 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551570 + GENEPIO:0101361 gene name (MPOX) orthopoxvirus gene 181 (MPOX) A gene name that denotes the opg181 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551571 + GENEPIO:0101362 gene name (MPOX) orthopoxvirus gene 185 (MPOX) A gene name that denotes the opg185 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551572 + GENEPIO:0101363 gene name (MPOX) orthopoxvirus gene 187 (MPOX) A gene name that denotes the opg187 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551573 + GENEPIO:0101364 gene name (MPOX) orthopoxvirus gene 188 (MPOX) A gene name that denotes the opg188 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551574 + GENEPIO:0101365 gene name (MPOX) orthopoxvirus gene 189 (MPOX) A gene name that denotes the opg189 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551575 + GENEPIO:0101366 gene name (MPOX) orthopoxvirus gene 190 (MPOX) A gene name that denotes the opg190 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551576 + GENEPIO:0101367 gene name (MPOX) orthopoxvirus gene 191 (MPOX) A gene name that denotes the opg191 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551577 + GENEPIO:0101368 gene name (MPOX) orthopoxvirus gene 192 (MPOX) A gene name that denotes the opg192 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551578 + GENEPIO:0101369 gene name (MPOX) orthopoxvirus gene 193 (MPOX) A gene name that denotes the opg193 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551579 + GENEPIO:0101370 gene name (MPOX) orthopoxvirus gene 195 (MPOX) A gene name that denotes the opg195 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551580 + GENEPIO:0101371 gene name (MPOX) orthopoxvirus gene 197 (MPOX) A gene name that denotes the opg197 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551581 + GENEPIO:0101372 gene name (MPOX) orthopoxvirus gene 198 (MPOX) A gene name that denotes the opg198 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551582 + GENEPIO:0101373 gene name (MPOX) orthopoxvirus gene 199 (MPOX) A gene name that denotes the opg199 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551583 + GENEPIO:0101374 gene name (MPOX) orthopoxvirus gene 200 (MPOX) A gene name that denotes the opg200 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551584 + GENEPIO:0101375 gene name (MPOX) orthopoxvirus gene 204 (MPOX) A gene name that denotes the opg204 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551585 + GENEPIO:0101376 gene name (MPOX) orthopoxvirus gene 205 (MPOX) A gene name that denotes the opg205 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551586 + GENEPIO:0101377 gene name (MPOX) orthopoxvirus gene 208 (MPOX) A gene name that denotes the opg208 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551587 + GENEPIO:0101378 gene name (MPOX) orthopoxvirus gene 209 (MPOX) A gene name that denotes the opg209 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551588 + GENEPIO:0101379 gene name (MPOX) orthopoxvirus gene 210 (MPOX) A gene name that denotes the opg210 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551589 + GENEPIO:0101380 gene name (MPOX) orthopoxvirus gene 005 (MPOX) A gene name that denotes the opg005 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551590 + GENEPIO:0101381 gene name (MPOX) orthopoxvirus gene 016 (MPOX) A gene name that denotes the opg016 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551591 + GENEPIO:0101382 gene symbol (MPOX) opg001 gene (MPOX) A gene symbol that denotes the opg001 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551607 + GENEPIO:0101382 gene symbol (MPOX) opg001 gene (MPOX) A gene symbol that denotes the opg001 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551595 + GENEPIO:0101383 gene symbol (MPOX) opg002 gene (MPOX) A gene symbol that denotes the opg002 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551418 + GENEPIO:0101383 gene symbol (MPOX) opg002 gene (MPOX) A gene symbol that denotes the opg002 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551594 + GENEPIO:0101384 gene symbol (MPOX) opg003 gene (MPOX) A gene symbol that denotes the opg003 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551419 + GENEPIO:0101384 gene symbol (MPOX) opg003 gene (MPOX) A gene symbol that denotes the opg003 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551593 + GENEPIO:0101385 gene symbol (MPOX) opg015 gene (MPOX) A gene symbol that denotes the opg015 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551420 + GENEPIO:0101385 gene symbol (MPOX) opg015 gene (MPOX) A gene symbol that denotes the opg015 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551592 + GENEPIO:0101386 gene symbol (MPOX) opg019 gene (MPOX) A gene symbol that denotes the opg019 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551421 + GENEPIO:0101387 gene symbol (MPOX) opg021 gene (MPOX) A gene symbol that denotes the opg021 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551422 + GENEPIO:0101388 gene symbol (MPOX) opg022 gene (MPOX) A gene symbol that denotes the opg022 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551423 + GENEPIO:0101389 gene symbol (MPOX) opg023 gene (MPOX) A gene symbol that denotes the opg023 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551424 + GENEPIO:0101390 gene symbol (MPOX) opg024 gene (MPOX) A gene symbol that denotes the opg024 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551425 + GENEPIO:0101391 gene symbol (MPOX) opg025 gene (MPOX) A gene symbol that denotes the opg025 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551426 + GENEPIO:0101392 gene symbol (MPOX) opg027 gene (MPOX) A gene symbol that denotes the opg027 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551427 + GENEPIO:0101393 gene symbol (MPOX) opg029 gene (MPOX) A gene symbol that denotes the opg029 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551428 + GENEPIO:0101394 gene symbol (MPOX) opg030 gene (MPOX) A gene symbol that denotes the opg030 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551429 + GENEPIO:0101395 gene symbol (MPOX) opg031 gene (MPOX) A gene symbol that denotes the opg031 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551430 + GENEPIO:0101396 gene symbol (MPOX) opg034 gene (MPOX) A gene symbol that denotes the opg034 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551431 + GENEPIO:0101397 gene symbol (MPOX) opg035 gene (MPOX) A gene symbol that denotes the opg035 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551432 + GENEPIO:0101399 gene symbol (MPOX) opg037 gene (MPOX) A gene symbol that denotes the opg037 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551434 + GENEPIO:0101400 gene symbol (MPOX) opg038 gene (MPOX) A gene symbol that denotes the opg038 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551435 + GENEPIO:0101401 gene symbol (MPOX) opg039 gene (MPOX) A gene symbol that denotes the opg039 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551436 + GENEPIO:0101402 gene symbol (MPOX) opg040 gene (MPOX) A gene symbol that denotes the opg040 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551437 + GENEPIO:0101403 gene symbol (MPOX) opg042 gene (MPOX) A gene symbol that denotes the opg042 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551438 + GENEPIO:0101404 gene symbol (MPOX) opg043 gene (MPOX) A gene symbol that denotes the opg043 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551439 + GENEPIO:0101406 gene symbol (MPOX) opg045 gene (MPOX) A gene symbol that denotes the opg045 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551441 + GENEPIO:0101407 gene symbol (MPOX) opg046 gene (MPOX) A gene symbol that denotes the opg046 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551442 + GENEPIO:0101408 gene symbol (MPOX) opg047 gene (MPOX) A gene symbol that denotes the opg047 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551443 + GENEPIO:0101409 gene symbol (MPOX) opg048 gene (MPOX) A gene symbol that denotes the opg048 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551444 + GENEPIO:0101410 gene symbol (MPOX) opg049 gene (MPOX) A gene symbol that denotes the opg049 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551445 + GENEPIO:0101411 gene symbol (MPOX) opg050 gene (MPOX) A gene symbol that denotes the opg050 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551446 + GENEPIO:0101412 gene symbol (MPOX) opg051 gene (MPOX) A gene symbol that denotes the opg051 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551447 + GENEPIO:0101413 gene symbol (MPOX) opg052 gene (MPOX) A gene symbol that denotes the opg052 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551448 + GENEPIO:0101414 gene symbol (MPOX) opg053 gene (MPOX) A gene symbol that denotes the opg053 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551449 + GENEPIO:0101415 gene symbol (MPOX) opg054 gene (MPOX) A gene symbol that denotes the opg054 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551450 + GENEPIO:0101416 gene symbol (MPOX) opg055 gene (MPOX) A gene symbol that denotes the opg055 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551451 + GENEPIO:0101417 gene symbol (MPOX) opg056 gene (MPOX) A gene symbol that denotes the opg056 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551452 + GENEPIO:0101418 gene symbol (MPOX) opg057 gene (MPOX) A gene symbol that denotes the opg057 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551453 + GENEPIO:0101419 gene symbol (MPOX) opg058 gene (MPOX) A gene symbol that denotes the opg058 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551454 + GENEPIO:0101420 gene symbol (MPOX) opg059 gene (MPOX) A gene symbol that denotes the opg059 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551455 + GENEPIO:0101421 gene symbol (MPOX) opg060 gene (MPOX) A gene symbol that denotes the opg060 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551456 + GENEPIO:0101422 gene symbol (MPOX) opg061 gene (MPOX) A gene symbol that denotes the opg061 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551457 + GENEPIO:0101423 gene symbol (MPOX) opg062 gene (MPOX) A gene symbol that denotes the opg062 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551458 + GENEPIO:0101424 gene symbol (MPOX) opg063 gene (MPOX) A gene symbol that denotes the opg063 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551459 + GENEPIO:0101425 gene symbol (MPOX) opg064 gene (MPOX) A gene symbol that denotes the opg064 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551460 + GENEPIO:0101426 gene symbol (MPOX) opg065 gene (MPOX) A gene symbol that denotes the opg065 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551461 + GENEPIO:0101427 gene symbol (MPOX) opg066 gene (MPOX) A gene symbol that denotes the opg066 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551462 + GENEPIO:0101428 gene symbol (MPOX) opg068 gene (MPOX) A gene symbol that denotes the opg068 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551463 + GENEPIO:0101429 gene symbol (MPOX) opg069 gene (MPOX) A gene symbol that denotes the opg069 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551464 + GENEPIO:0101430 gene symbol (MPOX) opg070 gene (MPOX) A gene symbol that denotes the opg070 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551465 + GENEPIO:0101431 gene symbol (MPOX) opg071 gene (MPOX) A gene symbol that denotes the opg071 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551466 + GENEPIO:0101432 gene symbol (MPOX) opg072 gene (MPOX) A gene symbol that denotes the opg072 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551467 + GENEPIO:0101433 gene symbol (MPOX) opg073 gene (MPOX) A gene symbol that denotes the opg073 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551468 + GENEPIO:0101434 gene symbol (MPOX) opg074 gene (MPOX) A gene symbol that denotes the opg074 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551469 + GENEPIO:0101435 gene symbol (MPOX) opg075 gene (MPOX) A gene symbol that denotes the opg075 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551470 + GENEPIO:0101437 gene symbol (MPOX) opg077 gene (MPOX) A gene symbol that denotes the opg077 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551472 + GENEPIO:0101438 gene symbol (MPOX) opg078 gene (MPOX) A gene symbol that denotes the opg078 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551473 + GENEPIO:0101439 gene symbol (MPOX) opg079 gene (MPOX) A gene symbol that denotes the opg079 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551474 + GENEPIO:0101440 gene symbol (MPOX) opg080 gene (MPOX) A gene symbol that denotes the opg080 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551475 + GENEPIO:0101441 gene symbol (MPOX) opg081 gene (MPOX) A gene symbol that denotes the opg081 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551476 + GENEPIO:0101442 gene symbol (MPOX) opg082 gene (MPOX) A gene symbol that denotes the opg082 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551477 + GENEPIO:0101443 gene symbol (MPOX) opg083 gene (MPOX) A gene symbol that denotes the opg083 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551478 + GENEPIO:0101444 gene symbol (MPOX) opg084 gene (MPOX) A gene symbol that denotes the opg084 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551479 + GENEPIO:0101445 gene symbol (MPOX) opg085 gene (MPOX) A gene symbol that denotes the opg085 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551480 + GENEPIO:0101446 gene symbol (MPOX) opg086 gene (MPOX) A gene symbol that denotes the opg086 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551481 + GENEPIO:0101447 gene symbol (MPOX) opg087 gene (MPOX) A gene symbol that denotes the opg087 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551482 + GENEPIO:0101448 gene symbol (MPOX) opg088 gene (MPOX) A gene symbol that denotes the opg088 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551483 + GENEPIO:0101449 gene symbol (MPOX) opg089 gene (MPOX) A gene symbol that denotes the opg089 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551484 + GENEPIO:0101450 gene symbol (MPOX) opg090 gene (MPOX) A gene symbol that denotes the opg090 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551485 + GENEPIO:0101451 gene symbol (MPOX) opg091 gene (MPOX) A gene symbol that denotes the opg091 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551486 + GENEPIO:0101452 gene symbol (MPOX) opg092 gene (MPOX) A gene symbol that denotes the opg092 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551487 + GENEPIO:0101453 gene symbol (MPOX) opg093 gene (MPOX) A gene symbol that denotes the opg093 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551488 + GENEPIO:0101454 gene symbol (MPOX) opg094 gene (MPOX) A gene symbol that denotes the opg094 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551489 + GENEPIO:0101455 gene symbol (MPOX) opg095 gene (MPOX) A gene symbol that denotes the opg095 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551490 + GENEPIO:0101456 gene symbol (MPOX) opg096 gene (MPOX) A gene symbol that denotes the opg096 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551491 + GENEPIO:0101457 gene symbol (MPOX) opg097 gene (MPOX) A gene symbol that denotes the opg097 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551492 + GENEPIO:0101458 gene symbol (MPOX) opg098 gene (MPOX) A gene symbol that denotes the opg098 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551493 + GENEPIO:0101459 gene symbol (MPOX) opg099 gene (MPOX) A gene symbol that denotes the opg099 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551494 + GENEPIO:0101460 gene symbol (MPOX) opg100 gene (MPOX) A gene symbol that denotes the opg100 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551495 + GENEPIO:0101461 gene symbol (MPOX) opg101 gene (MPOX) A gene symbol that denotes the opg101 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551496 + GENEPIO:0101462 gene symbol (MPOX) opg102 gene (MPOX) A gene symbol that denotes the opg102 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551497 + GENEPIO:0101463 gene symbol (MPOX) opg103 gene (MPOX) A gene symbol that denotes the opg103 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551498 + GENEPIO:0101464 gene symbol (MPOX) opg104 gene (MPOX) A gene symbol that denotes the opg104 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551499 + GENEPIO:0101465 gene symbol (MPOX) opg105 gene (MPOX) A gene symbol that denotes the opg105 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551500 + GENEPIO:0101466 gene symbol (MPOX) opg106 gene (MPOX) A gene symbol that denotes the opg106 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551501 + GENEPIO:0101467 gene symbol (MPOX) opg107 gene (MPOX) A gene symbol that denotes the opg107 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551502 + GENEPIO:0101468 gene symbol (MPOX) opg108 gene (MPOX) A gene symbol that denotes the opg108 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551503 + GENEPIO:0101469 gene symbol (MPOX) opg109 gene (MPOX) A gene symbol that denotes the opg109 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551504 + GENEPIO:0101470 gene symbol (MPOX) opg110 gene (MPOX) A gene symbol that denotes the opg110 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551505 + GENEPIO:0101471 gene symbol (MPOX) opg111 gene (MPOX) A gene symbol that denotes the opg111 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551506 + GENEPIO:0101472 gene symbol (MPOX) opg112 gene (MPOX) A gene symbol that denotes the opg112 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551507 + GENEPIO:0101473 gene symbol (MPOX) opg113 gene (MPOX) A gene symbol that denotes the opg113 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551508 + GENEPIO:0101474 gene symbol (MPOX) opg114 gene (MPOX) A gene symbol that denotes the opg114 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551509 + GENEPIO:0101475 gene symbol (MPOX) opg115 gene (MPOX) A gene symbol that denotes the opg115 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551510 + GENEPIO:0101476 gene symbol (MPOX) opg116 gene (MPOX) A gene symbol that denotes the opg116 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551511 + GENEPIO:0101477 gene symbol (MPOX) opg117 gene (MPOX) A gene symbol that denotes the opg117 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551512 + GENEPIO:0101478 gene symbol (MPOX) opg118 gene (MPOX) A gene symbol that denotes the opg118 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551513 + GENEPIO:0101479 gene symbol (MPOX) opg119 gene (MPOX) A gene symbol that denotes the opg119 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551514 + GENEPIO:0101480 gene symbol (MPOX) opg120 gene (MPOX) A gene symbol that denotes the opg120 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551515 + GENEPIO:0101481 gene symbol (MPOX) opg121 gene (MPOX) A gene symbol that denotes the opg121 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551516 + GENEPIO:0101482 gene symbol (MPOX) opg122 gene (MPOX) A gene symbol that denotes the opg122 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551517 + GENEPIO:0101483 gene symbol (MPOX) opg123 gene (MPOX) A gene symbol that denotes the opg123 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551518 + GENEPIO:0101484 gene symbol (MPOX) opg124 gene (MPOX) A gene symbol that denotes the opg124 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551519 + GENEPIO:0101485 gene symbol (MPOX) opg125 gene (MPOX) A gene symbol that denotes the opg125 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551520 + GENEPIO:0101486 gene symbol (MPOX) opg126 gene (MPOX) A gene symbol that denotes the opg126 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551521 + GENEPIO:0101487 gene symbol (MPOX) opg127 gene (MPOX) A gene symbol that denotes the opg127 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551522 + GENEPIO:0101488 gene symbol (MPOX) opg128 gene (MPOX) A gene symbol that denotes the opg128 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551523 + GENEPIO:0101489 gene symbol (MPOX) opg129 gene (MPOX) A gene symbol that denotes the opg129 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551524 + GENEPIO:0101490 gene symbol (MPOX) opg130 gene (MPOX) A gene symbol that denotes the opg130 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551525 + GENEPIO:0101491 gene symbol (MPOX) opg131 gene (MPOX) A gene symbol that denotes the opg131 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551526 + GENEPIO:0101492 gene symbol (MPOX) opg132 gene (MPOX) A gene symbol that denotes the opg132 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551527 + GENEPIO:0101493 gene symbol (MPOX) opg133 gene (MPOX) A gene symbol that denotes the opg133 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551528 + GENEPIO:0101494 gene symbol (MPOX) opg134 gene (MPOX) A gene symbol that denotes the opg134 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551529 + GENEPIO:0101495 gene symbol (MPOX) opg135 gene (MPOX) A gene symbol that denotes the opg135 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551530 + GENEPIO:0101496 gene symbol (MPOX) opg136 gene (MPOX) A gene symbol that denotes the opg136 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551531 + GENEPIO:0101497 gene symbol (MPOX) opg137 gene (MPOX) A gene symbol that denotes the opg137 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551532 + GENEPIO:0101498 gene symbol (MPOX) opg138 gene (MPOX) A gene symbol that denotes the opg138 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551533 + GENEPIO:0101499 gene symbol (MPOX) opg139 gene (MPOX) A gene symbol that denotes the opg139 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551534 + GENEPIO:0101500 gene symbol (MPOX) opg140 gene (MPOX) A gene symbol that denotes the opg140 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551535 + GENEPIO:0101501 gene symbol (MPOX) opg141 gene (MPOX) A gene symbol that denotes the opg141 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551536 + GENEPIO:0101502 gene symbol (MPOX) opg142 gene (MPOX) A gene symbol that denotes the opg142 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551537 + GENEPIO:0101503 gene symbol (MPOX) opg143 gene (MPOX) A gene symbol that denotes the opg143 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551538 + GENEPIO:0101504 gene symbol (MPOX) opg144 gene (MPOX) A gene symbol that denotes the opg144 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551539 + GENEPIO:0101505 gene symbol (MPOX) opg145 gene (MPOX) A gene symbol that denotes the opg145 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551540 + GENEPIO:0101506 gene symbol (MPOX) opg146 gene (MPOX) A gene symbol that denotes the opg146 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551541 + GENEPIO:0101507 gene symbol (MPOX) opg147 gene (MPOX) A gene symbol that denotes the opg147 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551542 + GENEPIO:0101508 gene symbol (MPOX) opg148 gene (MPOX) A gene symbol that denotes the opg148 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551543 + GENEPIO:0101509 gene symbol (MPOX) opg149 gene (MPOX) A gene symbol that denotes the opg149 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551544 + GENEPIO:0101510 gene symbol (MPOX) opg150 gene (MPOX) A gene symbol that denotes the opg150 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551545 + GENEPIO:0101511 gene symbol (MPOX) opg151 gene (MPOX) A gene symbol that denotes the opg151 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551546 + GENEPIO:0101512 gene symbol (MPOX) opg153 gene (MPOX) A gene symbol that denotes the opg153 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551547 + GENEPIO:0101513 gene symbol (MPOX) opg154 gene (MPOX) A gene symbol that denotes the opg154 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551548 + GENEPIO:0101514 gene symbol (MPOX) opg155 gene (MPOX) A gene symbol that denotes the opg155 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551549 + GENEPIO:0101515 gene symbol (MPOX) opg156 gene (MPOX) A gene symbol that denotes the opg156 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551550 + GENEPIO:0101516 gene symbol (MPOX) opg157 gene (MPOX) A gene symbol that denotes the opg157 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551551 + GENEPIO:0101517 gene symbol (MPOX) opg158 gene (MPOX) A gene symbol that denotes the opg158 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551552 + GENEPIO:0101518 gene symbol (MPOX) opg159 gene (MPOX) A gene symbol that denotes the opg159 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551553 + GENEPIO:0101519 gene symbol (MPOX) opg160 gene (MPOX) A gene symbol that denotes the opg160 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551554 + GENEPIO:0101520 gene symbol (MPOX) opg161 gene (MPOX) A gene symbol that denotes the opg161 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551555 + GENEPIO:0101521 gene symbol (MPOX) opg162 gene (MPOX) A gene symbol that denotes the opg162 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551556 + GENEPIO:0101522 gene symbol (MPOX) opg163 gene (MPOX) A gene symbol that denotes the opg163 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551557 + GENEPIO:0101523 gene symbol (MPOX) opg164 gene (MPOX) A gene symbol that denotes the opg164 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551558 + GENEPIO:0101524 gene symbol (MPOX) opg165 gene (MPOX) A gene symbol that denotes the opg165 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551559 + GENEPIO:0101525 gene symbol (MPOX) opg166 gene (MPOX) A gene symbol that denotes the opg166 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551560 + GENEPIO:0101526 gene symbol (MPOX) opg167 gene (MPOX) A gene symbol that denotes the opg167 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551561 + GENEPIO:0101527 gene symbol (MPOX) opg170 gene (MPOX) A gene symbol that denotes the opg170 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551562 + GENEPIO:0101528 gene symbol (MPOX) opg171 gene (MPOX) A gene symbol that denotes the opg171 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551563 + GENEPIO:0101529 gene symbol (MPOX) opg172 gene (MPOX) A gene symbol that denotes the opg172 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551564 + GENEPIO:0101530 gene symbol (MPOX) opg173 gene (MPOX) A gene symbol that denotes the opg173 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551565 + GENEPIO:0101531 gene symbol (MPOX) opg174 gene (MPOX) A gene symbol that denotes the opg174 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551566 + GENEPIO:0101532 gene symbol (MPOX) opg175 gene (MPOX) A gene symbol that denotes the opg175 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551567 + GENEPIO:0101533 gene symbol (MPOX) opg176 gene (MPOX) A gene symbol that denotes the opg176 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551568 + GENEPIO:0101534 gene symbol (MPOX) opg178 gene (MPOX) A gene symbol that denotes the opg178 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551569 + GENEPIO:0101535 gene symbol (MPOX) opg180 gene (MPOX) A gene symbol that denotes the opg180 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551570 + GENEPIO:0101536 gene symbol (MPOX) opg181 gene (MPOX) A gene symbol that denotes the opg181 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551571 + GENEPIO:0101537 gene symbol (MPOX) opg185 gene (MPOX) A gene symbol that denotes the opg185 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551572 + GENEPIO:0101538 gene symbol (MPOX) opg187 gene (MPOX) A gene symbol that denotes the opg187 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551573 + GENEPIO:0101539 gene symbol (MPOX) opg188 gene (MPOX) A gene symbol that denotes the opg188 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551574 + GENEPIO:0101540 gene symbol (MPOX) opg189 gene (MPOX) A gene symbol that denotes the opg189 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551575 + GENEPIO:0101541 gene symbol (MPOX) opg190 gene (MPOX) A gene symbol that denotes the opg190 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551576 + GENEPIO:0101542 gene symbol (MPOX) opg191 gene (MPOX) A gene symbol that denotes the opg191 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551577 + GENEPIO:0101543 gene symbol (MPOX) opg192 gene (MPOX) A gene symbol that denotes the opg192 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551578 + GENEPIO:0101544 gene symbol (MPOX) opg193 gene (MPOX) A gene symbol that denotes the opg193 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551579 + GENEPIO:0101545 gene symbol (MPOX) opg195 gene (MPOX) A gene symbol that denotes the opg195 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551580 + GENEPIO:0101546 gene symbol (MPOX) opg197 gene (MPOX) A gene symbol that denotes the opg197 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551581 + GENEPIO:0101547 gene symbol (MPOX) opg198 gene (MPOX) A gene symbol that denotes the opg198 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551582 + GENEPIO:0101548 gene symbol (MPOX) opg199 gene (MPOX) A gene symbol that denotes the opg199 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551583 + GENEPIO:0101549 gene symbol (MPOX) opg200 gene (MPOX) A gene symbol that denotes the opg200 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551584 + GENEPIO:0101550 gene symbol (MPOX) opg204 gene (MPOX) A gene symbol that denotes the opg204 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551585 + GENEPIO:0101551 gene symbol (MPOX) opg205 gene (MPOX) A gene symbol that denotes the opg205 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551586 + GENEPIO:0101552 gene symbol (MPOX) opg208 gene (MPOX) A gene symbol that denotes the opg208 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551587 + GENEPIO:0101553 gene symbol (MPOX) opg209 gene (MPOX) A gene symbol that denotes the opg209 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551588 + GENEPIO:0101554 gene symbol (MPOX) opg210 gene (MPOX) A gene symbol that denotes the opg210 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551589 + GENEPIO:0101555 gene symbol (MPOX) opg005 gene (MPOX) A gene symbol that denotes the opg005 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551590 + GENEPIO:0101556 gene symbol (MPOX) opg016 gene (MPOX) A gene symbol that denotes the opg016 gene (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GeneID:72551591 + GENEPIO:0101557 protein name (MPOX) Chemokine binding protein (MPOX) A protein name that denotes the Chemokine binding protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377002.1,GeneID:72551607 + GENEPIO:0101557 protein name (MPOX) Chemokine binding protein (MPOX) A protein name that denotes the Chemokine binding protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377148.1,GeneID:72551562 + GENEPIO:0101557 protein name (MPOX) Chemokine binding protein (MPOX) A protein name that denotes the Chemokine binding protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377182.1,GeneID:72551595 + GENEPIO:0101558 protein name (MPOX) Crm-B secreted TNF-alpha-receptor-like protein (MPOX) A protein name that denotes the Crm-B secreted TNF-alpha-receptor-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377003.1,GeneID:72551418 + GENEPIO:0101558 protein name (MPOX) Crm-B secreted TNF-alpha-receptor-like protein (MPOX) A protein name that denotes the Crm-B secreted TNF-alpha-receptor-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377181.1,GeneID:72551594 + GENEPIO:0101559 protein name (MPOX) Ankyrin repeat protein (25) (MPOX) A protein name that denotes the Ankyrin repeat protein (25) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377004.1,GeneID:72551419 + GENEPIO:0101559 protein name (MPOX) Ankyrin repeat protein (25) (MPOX) A protein name that denotes the Ankyrin repeat protein (25) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377161.1,GeneID:72551575 + GENEPIO:0101559 protein name (MPOX) Ankyrin repeat protein (25) (MPOX) A protein name that denotes the Ankyrin repeat protein (25) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377180.1,GeneID:72551593 + GENEPIO:0101560 protein name (MPOX) Ankyrin repeat protein (39) (MPOX) A protein name that denotes the Ankyrin repeat protein (39) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377005.1,GeneID:72551420 + GENEPIO:0101560 protein name (MPOX) Ankyrin repeat protein (39) (MPOX) A protein name that denotes the Ankyrin repeat protein (39) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377179.1,GeneID:72551592 + GENEPIO:0101561 protein name (MPOX) EGF-like domain protein (MPOX) A protein name that denotes the EGF-like domain protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377006.1,GeneID:72551421 + GENEPIO:0101562 protein name (MPOX) Zinc finger-like protein (2) (MPOX) A protein name that denotes the Zinc finger-like protein (2) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377007.1,GeneID:72551422 + GENEPIO:0101563 protein name (MPOX) Interleukin-18-binding protein (MPOX) A protein name that denotes the Interleukin-18-binding protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377008.1,GeneID:72551423 + GENEPIO:0101564 protein name (MPOX) Ankyrin repeat protein (2) (MPOX) A protein name that denotes the Ankyrin repeat protein (2) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377009.1,GeneID:72551424 + GENEPIO:0101565 protein name (MPOX) retroviral pseudoprotease-like protein (MPOX) A protein name that denotes the retroviral pseudoprotease-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377010.1,GeneID:72551425 + GENEPIO:0101566 protein name (MPOX) Ankyrin repeat protein (14) (MPOX) A protein name that denotes the Ankyrin repeat protein (14) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377011.1,GeneID:72551426 + GENEPIO:0101567 protein name (MPOX) Host range protein (MPOX) A protein name that denotes the Host range protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377012.1,GeneID:72551427 + GENEPIO:0101568 protein name (MPOX) Bcl-2-like protein (MPOX) A protein name that denotes the Bcl-2-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377013.1,GeneID:72551428 + GENEPIO:0101568 protein name (MPOX) Bcl-2-like protein (MPOX) A protein name that denotes the Bcl-2-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377017.1,GeneID:72551431 + GENEPIO:0101568 protein name (MPOX) Bcl-2-like protein (MPOX) A protein name that denotes the Bcl-2-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377018.1,GeneID:72551432 + GENEPIO:0101568 protein name (MPOX) Bcl-2-like protein (MPOX) A protein name that denotes the Bcl-2-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377154.1,GeneID:72551568 + GENEPIO:0101568 protein name (MPOX) Bcl-2-like protein (MPOX) A protein name that denotes the Bcl-2-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377170.1,GeneID:72551584 + GENEPIO:0101568 protein name (MPOX) Bcl-2-like protein (MPOX) A protein name that denotes the Bcl-2-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377177.1,GeneID:72551590 + GENEPIO:0101569 protein name (MPOX) Kelch-like protein (1) (MPOX) A protein name that denotes the Kelch-like protein (1) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377014.1,GeneID:72551429 + GENEPIO:0101570 protein name (MPOX) C4L/C10L-like family protein (MPOX) A protein name that denotes the C4L/C10L-like family protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377015.1,GeneID:72551430 + GENEPIO:0101571 protein name (MPOX) Ankyrin-like protein (1) (MPOX) A protein name that denotes the Ankyrin-like protein (1) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377020.1,GeneID:72551434 + GENEPIO:0101572 protein name (MPOX) NFkB inhibitor protein (MPOX) A protein name that denotes the NFkB inhibitor protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377021.1,GeneID:72551435 + GENEPIO:0101573 protein name (MPOX) Ankyrin-like protein (3) (MPOX) A protein name that denotes the Ankyrin-like protein (3) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377022.1,GeneID:72551436 + GENEPIO:0101574 protein name (MPOX) Serpin protein (MPOX) A protein name that denotes the Serpin protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377023.1,GeneID:72551437 + GENEPIO:0101574 protein name (MPOX) Serpin protein (MPOX) A protein name that denotes the Serpin protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377169.1,GeneID:72551583 + GENEPIO:0101574 protein name (MPOX) Serpin protein (MPOX) A protein name that denotes the Serpin protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377174.1,GeneID:72551587 + GENEPIO:0101575 protein name (MPOX) Phospholipase-D-like protein (MPOX) A protein name that denotes the Phospholipase-D-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377025.1,GeneID:72551438 + GENEPIO:0101576 protein name (MPOX) Putative monoglyceride lipase protein (MPOX) A protein name that denotes the Putative monoglyceride lipase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377026.1,GeneID:72551439 + GENEPIO:0101577 protein name (MPOX) Caspase-9 inhibitor protein (MPOX) A protein name that denotes the Caspase-9 inhibitor protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377028.1,GeneID:72551441 + GENEPIO:0101578 protein name (MPOX) dUTPase protein (MPOX) A protein name that denotes the dUTPase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377029.1,GeneID:72551442 + GENEPIO:0101579 protein name (MPOX) Kelch-like protein (2) (MPOX) A protein name that denotes the Kelch-like protein (2) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377030.1,GeneID:72551443 + GENEPIO:0101580 protein name (MPOX) Ribonucleotide reductase small subunit protein (MPOX) A protein name that denotes the Ribonucleotide reductase small subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377031.1,GeneID:72551444 + GENEPIO:0101581 protein name (MPOX) Telomere-binding protein I6 (1) (MPOX) A protein name that denotes the Telomere-binding protein I6 (1) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377032.1,GeneID:72551445 + GENEPIO:0101582 protein name (MPOX) CPXV053 protein (MPOX) A protein name that denotes the CPXV053 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377033.1,GeneID:72551446 + GENEPIO:0101583 protein name (MPOX) CPXV054 protein (MPOX) A protein name that denotes the CPXV054 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377034.1,GeneID:72551447 + GENEPIO:0101584 protein name (MPOX) Cytoplasmic protein (MPOX) A protein name that denotes the Cytoplasmic protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377035.1,GeneID:72551448 + GENEPIO:0101585 protein name (MPOX) IMV membrane protein L1R (MPOX) A protein name that denotes the IMV membrane protein L1R (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377036.1,GeneID:72551449 + GENEPIO:0101585 protein name (MPOX) IMV membrane protein L1R (MPOX) A protein name that denotes the IMV membrane protein L1R (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377077.1,GeneID:72551490 + GENEPIO:0101586 protein name (MPOX) Serine/threonine-protein kinase (MPOX) A protein name that denotes the Serine/threonine-protein kinase (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377037.1,GeneID:72551450 + GENEPIO:0101587 protein name (MPOX) Protein F11 protein (MPOX) A protein name that denotes the Protein F11 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377038.1,GeneID:72551451 + GENEPIO:0101588 protein name (MPOX) EEV maturation protein (MPOX) A protein name that denotes the EEV maturation protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377039.1,GeneID:72551452 + GENEPIO:0101589 protein name (MPOX) Palmytilated EEV membrane protein (MPOX) A protein name that denotes the Palmytilated EEV membrane protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377040.1,GeneID:72551453 + GENEPIO:0101590 protein name (MPOX) Protein F14 (1) protein (MPOX) A protein name that denotes the Protein F14 (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377041.1,GeneID:72551454 + GENEPIO:0101591 protein name (MPOX) Cytochrome C oxidase protein (MPOX) A protein name that denotes the Cytochrome C oxidase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377042.1,GeneID:72551455 + GENEPIO:0101592 protein name (MPOX) Protein F15 protein (MPOX) A protein name that denotes the Protein F15 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377043.1,GeneID:72551456 + GENEPIO:0101593 protein name (MPOX) Protein F16 (1) protein (MPOX) A protein name that denotes the Protein F16 (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377044.1,GeneID:72551457 + GENEPIO:0101594 protein name (MPOX) DNA-binding phosphoprotein (1) (MPOX) A protein name that denotes the DNA-binding phosphoprotein (1) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377045.1,GeneID:72551458 + GENEPIO:0101595 protein name (MPOX) Poly(A) polymerase catalytic subunit (3) protein (MPOX) A protein name that denotes the Poly(A) polymerase catalytic subunit (3) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377046.1,GeneID:72551459 + GENEPIO:0101596 protein name (MPOX) Iev morphogenesis protein (MPOX) A protein name that denotes the Iev morphogenesis protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377047.1,GeneID:72551460 + GENEPIO:0101596 protein name (MPOX) Iev morphogenesis protein (MPOX) A protein name that denotes the Iev morphogenesis protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377057.1,GeneID:72551469 + GENEPIO:0101597 protein name (MPOX) Double-stranded RNA binding protein (MPOX) A protein name that denotes the Double-stranded RNA binding protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377048.1,GeneID:72551461 + GENEPIO:0101598 protein name (MPOX) DNA-directed RNA polymerase 30 kDa polypeptide protein (MPOX) A protein name that denotes the DNA-directed RNA polymerase 30 kDa polypeptide protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377049.1,GeneID:72551462 + GENEPIO:0101599 protein name (MPOX) IMV membrane protein E6 (MPOX) A protein name that denotes the IMV membrane protein E6 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377051.1,GeneID:72551463 + GENEPIO:0101600 protein name (MPOX) Myristoylated protein E7 (MPOX) A protein name that denotes the Myristoylated protein E7 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377052.1,GeneID:72551464 + GENEPIO:0101601 protein name (MPOX) Membrane protein E8 (MPOX) A protein name that denotes the Membrane protein E8 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377053.1,GeneID:72551465 + GENEPIO:0101602 protein name (MPOX) DNA polymerase (2) protein (MPOX) A protein name that denotes the DNA polymerase (2) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377054.1,GeneID:72551466 + GENEPIO:0101603 protein name (MPOX) Sulfhydryl oxidase protein (MPOX) A protein name that denotes the Sulfhydryl oxidase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377055.1,GeneID:72551467 + GENEPIO:0101604 protein name (MPOX) Virion core protein E11 (MPOX) A protein name that denotes the Virion core protein E11 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377056.1,GeneID:72551468 + GENEPIO:0101605 protein name (MPOX) Glutaredoxin-1 protein (MPOX) A protein name that denotes the Glutaredoxin-1 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377058.1,GeneID:72551470 + GENEPIO:0101607 protein name (MPOX) Telomere-binding protein I1 (MPOX) A protein name that denotes the Telomere-binding protein I1 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377059.1,GeneID:72551472 + GENEPIO:0101608 protein name (MPOX) IMV membrane protein I2 (MPOX) A protein name that denotes the IMV membrane protein I2 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377060.1,GeneID:72551473 + GENEPIO:0101609 protein name (MPOX) DNA-binding phosphoprotein (2) (MPOX) A protein name that denotes the DNA-binding phosphoprotein (2) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377061.1,GeneID:72551474 + GENEPIO:0101610 protein name (MPOX) Ribonucleoside-diphosphate reductase (2) protein (MPOX) A protein name that denotes the Ribonucleoside-diphosphate reductase (2) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377062.1,GeneID:72551475 + GENEPIO:0101611 protein name (MPOX) IMV membrane protein I5 (MPOX) A protein name that denotes the IMV membrane protein I5 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377063.1,GeneID:72551476 + GENEPIO:0101612 protein name (MPOX) Telomere-binding protein (MPOX) A protein name that denotes the Telomere-binding protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377064.1,GeneID:72551477 + GENEPIO:0101613 protein name (MPOX) Viral core cysteine proteinase (MPOX) A protein name that denotes the Viral core cysteine proteinase (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377065.1,GeneID:72551478 + GENEPIO:0101614 protein name (MPOX) RNA helicase NPH-II (2) protein (MPOX) A protein name that denotes the RNA helicase NPH-II (2) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377066.1,GeneID:72551479 + GENEPIO:0101615 protein name (MPOX) Metalloendopeptidase protein (MPOX) A protein name that denotes the Metalloendopeptidase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377067.1,GeneID:72551480 + GENEPIO:0101616 protein name (MPOX) Entry/fusion complex component protein (MPOX) A protein name that denotes the Entry/fusion complex component protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377068.1,GeneID:72551481 + GENEPIO:0101617 protein name (MPOX) Late transcription elongation factor protein (MPOX) A protein name that denotes the Late transcription elongation factor protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377069.1,GeneID:72551482 + GENEPIO:0101618 protein name (MPOX) Glutaredoxin-2 protein (MPOX) A protein name that denotes the Glutaredoxin-2 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377070.1,GeneID:72551483 + GENEPIO:0101619 protein name (MPOX) FEN1-like nuclease protein (MPOX) A protein name that denotes the FEN1-like nuclease protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377071.1,GeneID:72551484 + GENEPIO:0101620 protein name (MPOX) DNA-directed RNA polymerase 7 kDa subunit protein (MPOX) A protein name that denotes the DNA-directed RNA polymerase 7 kDa subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377072.1,GeneID:72551485 + GENEPIO:0101621 protein name (MPOX) Nlpc/p60 superfamily protein (MPOX) A protein name that denotes the Nlpc/p60 superfamily protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377073.1,GeneID:72551486 + GENEPIO:0101622 protein name (MPOX) Assembly protein G7 (MPOX) A protein name that denotes the Assembly protein G7 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377074.1,GeneID:72551487 + GENEPIO:0101623 protein name (MPOX) Late transcription factor VLTF-1 protein (MPOX) A protein name that denotes the Late transcription factor VLTF-1 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377075.1,GeneID:72551488 + GENEPIO:0101624 protein name (MPOX) Myristylated protein (MPOX) A protein name that denotes the Myristylated protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377076.1,GeneID:72551489 + GENEPIO:0101624 protein name (MPOX) Myristylated protein (MPOX) A protein name that denotes the Myristylated protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377086.1,GeneID:72551499 + GENEPIO:0101624 protein name (MPOX) Myristylated protein (MPOX) A protein name that denotes the Myristylated protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377125.1,GeneID:72551538 + GENEPIO:0101625 protein name (MPOX) Crescent membrane and immature virion formation protein (MPOX) A protein name that denotes the Crescent membrane and immature virion formation protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377078.1,GeneID:72551491 + GENEPIO:0101626 protein name (MPOX) Internal virion L3/FP4 protein (MPOX) A protein name that denotes the Internal virion L3/FP4 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377079.1,GeneID:72551492 + GENEPIO:0101627 protein name (MPOX) Nucleic acid binding protein VP8/L4R (MPOX) A protein name that denotes the Nucleic acid binding protein VP8/L4R (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377080.1,GeneID:72551493 + GENEPIO:0101628 protein name (MPOX) Membrane protein CL5 (MPOX) A protein name that denotes the Membrane protein CL5 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377081.1,GeneID:72551494 + GENEPIO:0101629 protein name (MPOX) IMV membrane protein J1 (MPOX) A protein name that denotes the IMV membrane protein J1 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377082.1,GeneID:72551495 + GENEPIO:0101630 protein name (MPOX) Thymidine kinase protein (MPOX) A protein name that denotes the Thymidine kinase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377083.1,GeneID:72551496 + GENEPIO:0101631 protein name (MPOX) Cap-specific mRNA protein (MPOX) A protein name that denotes the Cap-specific mRNA protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377084.1,GeneID:72551497 + GENEPIO:0101632 protein name (MPOX) DNA-directed RNA polymerase subunit protein (MPOX) A protein name that denotes the DNA-directed RNA polymerase subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377085.1,GeneID:72551498 + GENEPIO:0101633 protein name (MPOX) DNA-dependent RNA polymerase subunit rpo147 protein (MPOX) A protein name that denotes the DNA-dependent RNA polymerase subunit rpo147 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377087.1,GeneID:72551500 + GENEPIO:0101634 protein name (MPOX) Tyr/ser protein phosphatase (MPOX) A protein name that denotes the Tyr/ser protein phosphatase (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377088.1,GeneID:72551501 + GENEPIO:0101635 protein name (MPOX) Entry-fusion complex essential component protein (MPOX) A protein name that denotes the Entry-fusion complex essential component protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377089.1,GeneID:72551502 + GENEPIO:0101636 protein name (MPOX) IMV heparin binding surface protein (MPOX) A protein name that denotes the IMV heparin binding surface protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377090.1,GeneID:72551503 + GENEPIO:0101637 protein name (MPOX) RNA polymerase-associated transcription-specificity factor RAP94 protein (MPOX) A protein name that denotes the RNA polymerase-associated transcription-specificity factor RAP94 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377091.1,GeneID:72551504 + GENEPIO:0101638 protein name (MPOX) Late transcription factor VLTF-4 (1) protein (MPOX) A protein name that denotes the Late transcription factor VLTF-4 (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377092.1,GeneID:72551505 + GENEPIO:0101639 protein name (MPOX) DNA topoisomerase type I protein (MPOX) A protein name that denotes the DNA topoisomerase type I protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377093.1,GeneID:72551506 + GENEPIO:0101640 protein name (MPOX) Late protein H7 (MPOX) A protein name that denotes the Late protein H7 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377094.1,GeneID:72551507 + GENEPIO:0101641 protein name (MPOX) mRNA capping enzyme large subunit protein (MPOX) A protein name that denotes the mRNA capping enzyme large subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377095.1,GeneID:72551508 + GENEPIO:0101642 protein name (MPOX) Virion protein D2 (MPOX) A protein name that denotes the Virion protein D2 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377096.1,GeneID:72551509 + GENEPIO:0101643 protein name (MPOX) Virion core protein D3 (MPOX) A protein name that denotes the Virion core protein D3 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377097.1,GeneID:72551510 + GENEPIO:0101644 protein name (MPOX) Uracil DNA glycosylase superfamily protein (MPOX) A protein name that denotes the Uracil DNA glycosylase superfamily protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377098.1,GeneID:72551511 + GENEPIO:0101645 protein name (MPOX) NTPase (1) protein (MPOX) A protein name that denotes the NTPase (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377099.1,GeneID:72551512 + GENEPIO:0101646 protein name (MPOX) Early transcription factor 70 kDa subunit protein (MPOX) A protein name that denotes the Early transcription factor 70 kDa subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377100.1,GeneID:72551513 + GENEPIO:0101647 protein name (MPOX) RNA polymerase subunit RPO18 protein (MPOX) A protein name that denotes the RNA polymerase subunit RPO18 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377101.1,GeneID:72551514 + GENEPIO:0101648 protein name (MPOX) Carbonic anhydrase protein (MPOX) A protein name that denotes the Carbonic anhydrase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377102.1,GeneID:72551515 + GENEPIO:0101649 protein name (MPOX) NUDIX domain protein (MPOX) A protein name that denotes the NUDIX domain protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377103.1,GeneID:72551516 + GENEPIO:0101650 protein name (MPOX) MutT motif protein (MPOX) A protein name that denotes the MutT motif protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377104.1,GeneID:72551517 + GENEPIO:0101651 protein name (MPOX) Nucleoside triphosphatase I protein (MPOX) A protein name that denotes the Nucleoside triphosphatase I protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377105.1,GeneID:72551518 + GENEPIO:0101652 protein name (MPOX) mRNA capping enzyme small subunit protein (MPOX) A protein name that denotes the mRNA capping enzyme small subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377106.1,GeneID:72551519 + GENEPIO:0101653 protein name (MPOX) Rifampicin resistance protein (MPOX) A protein name that denotes the Rifampicin resistance protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377107.1,GeneID:72551520 + GENEPIO:0101654 protein name (MPOX) Late transcription factor VLTF-2 (2) protein (MPOX) A protein name that denotes the Late transcription factor VLTF-2 (2) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377108.1,GeneID:72551521 + GENEPIO:0101655 protein name (MPOX) Late transcription factor VLTF-3 (1) protein (MPOX) A protein name that denotes the Late transcription factor VLTF-3 (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377109.1,GeneID:72551522 + GENEPIO:0101656 protein name (MPOX) S-S bond formation pathway protein (MPOX) A protein name that denotes the S-S bond formation pathway protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377110.1,GeneID:72551523 + GENEPIO:0101657 protein name (MPOX) Virion core protein P4b (MPOX) A protein name that denotes the Virion core protein P4b (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377111.1,GeneID:72551524 + GENEPIO:0101658 protein name (MPOX) A5L protein-like (MPOX) A protein name that denotes the A5L protein-like (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377112.1,GeneID:72551525 + GENEPIO:0101659 protein name (MPOX) DNA-directed RNA polymerase 19 kDa subunit protein (MPOX) A protein name that denotes the DNA-directed RNA polymerase 19 kDa subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377113.1,GeneID:72551526 + GENEPIO:0101660 protein name (MPOX) Virion morphogenesis protein (MPOX) A protein name that denotes the Virion morphogenesis protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377114.1,GeneID:72551527 + GENEPIO:0101661 protein name (MPOX) Early transcription factor 82 kDa subunit protein (MPOX) A protein name that denotes the Early transcription factor 82 kDa subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377115.1,GeneID:72551528 + GENEPIO:0101662 protein name (MPOX) Intermediate transcription factor VITF-3 (1) protein (MPOX) A protein name that denotes the Intermediate transcription factor VITF-3 (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377116.1,GeneID:72551529 + GENEPIO:0101663 protein name (MPOX) IMV membrane protein A9 (MPOX) A protein name that denotes the IMV membrane protein A9 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377117.1,GeneID:72551530 + GENEPIO:0101664 protein name (MPOX) Virion core protein P4a (MPOX) A protein name that denotes the Virion core protein P4a (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377118.1,GeneID:72551531 + GENEPIO:0101665 protein name (MPOX) Viral membrane formation protein (MPOX) A protein name that denotes the Viral membrane formation protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377119.1,GeneID:72551532 + GENEPIO:0101666 protein name (MPOX) A12 protein (MPOX) A protein name that denotes the A12 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377120.1,GeneID:72551533 + GENEPIO:0101667 protein name (MPOX) IMV membrane protein A13L (MPOX) A protein name that denotes the IMV membrane protein A13L (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377121.1,GeneID:72551534 + GENEPIO:0101668 protein name (MPOX) IMV membrane protein A14 (MPOX) A protein name that denotes the IMV membrane protein A14 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377122.1,GeneID:72551535 + GENEPIO:0101669 protein name (MPOX) DUF1029 domain protein (MPOX) A protein name that denotes the DUF1029 domain protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377123.1,GeneID:72551536 + GENEPIO:0101670 protein name (MPOX) Core protein A15 (MPOX) A protein name that denotes the Core protein A15 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377124.1,GeneID:72551537 + GENEPIO:0101671 protein name (MPOX) IMV membrane protein P21 (MPOX) A protein name that denotes the IMV membrane protein P21 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377126.1,GeneID:72551539 + GENEPIO:0101672 protein name (MPOX) DNA helicase protein (MPOX) A protein name that denotes the DNA helicase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377127.1,GeneID:72551540 + GENEPIO:0101673 protein name (MPOX) Zinc finger-like protein (1) (MPOX) A protein name that denotes the Zinc finger-like protein (1) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377128.1,GeneID:72551541 + GENEPIO:0101674 protein name (MPOX) IMV membrane protein A21 (MPOX) A protein name that denotes the IMV membrane protein A21 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377129.1,GeneID:72551542 + GENEPIO:0101675 protein name (MPOX) DNA polymerase processivity factor protein (MPOX) A protein name that denotes the DNA polymerase processivity factor protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377130.1,GeneID:72551543 + GENEPIO:0101676 protein name (MPOX) Holliday junction resolvase protein (MPOX) A protein name that denotes the Holliday junction resolvase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377131.1,GeneID:72551544 + GENEPIO:0101677 protein name (MPOX) Intermediate transcription factor VITF-3 (2) protein (MPOX) A protein name that denotes the Intermediate transcription factor VITF-3 (2) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377132.1,GeneID:72551545 + GENEPIO:0101678 protein name (MPOX) DNA-dependent RNA polymerase subunit rpo132 protein (MPOX) A protein name that denotes the DNA-dependent RNA polymerase subunit rpo132 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377133.1,GeneID:72551546 + GENEPIO:0101679 protein name (MPOX) Orthopoxvirus A26L/A30L protein (MPOX) A protein name that denotes the Orthopoxvirus A26L/A30L protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377134.1,GeneID:72551547 + GENEPIO:0101680 protein name (MPOX) IMV surface fusion protein (MPOX) A protein name that denotes the IMV surface fusion protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377135.1,GeneID:72551548 + GENEPIO:0101681 protein name (MPOX) Envelope protein A28 homolog (MPOX) A protein name that denotes the Envelope protein A28 homolog (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377136.1,GeneID:72551549 + GENEPIO:0101682 protein name (MPOX) DNA-directed RNA polymerase 35 kDa subunit protein (MPOX) A protein name that denotes the DNA-directed RNA polymerase 35 kDa subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377137.1,GeneID:72551550 + GENEPIO:0101683 protein name (MPOX) IMV membrane protein A30 (MPOX) A protein name that denotes the IMV membrane protein A30 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377138.1,GeneID:72551551 + GENEPIO:0101684 protein name (MPOX) A32.5L protein (MPOX) A protein name that denotes the A32.5L protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377139.1,GeneID:72551552 + GENEPIO:0101685 protein name (MPOX) CPXV166 protein (MPOX) A protein name that denotes the CPXV166 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377140.1,GeneID:72551553 + GENEPIO:0101686 protein name (MPOX) ATPase A32 protein (MPOX) A protein name that denotes the ATPase A32 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377141.1,GeneID:72551554 + GENEPIO:0101687 protein name (MPOX) EEV glycoprotein (1) (MPOX) A protein name that denotes the EEV glycoprotein (1) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377142.1,GeneID:72551555 + GENEPIO:0101688 protein name (MPOX) EEV glycoprotein (2) (MPOX) A protein name that denotes the EEV glycoprotein (2) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377143.1,GeneID:72551556 + GENEPIO:0101689 protein name (MPOX) MHC class II antigen presentation inhibitor protein (MPOX) A protein name that denotes the MHC class II antigen presentation inhibitor protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377144.1,GeneID:72551557 + GENEPIO:0101690 protein name (MPOX) IEV transmembrane phosphoprotein (MPOX) A protein name that denotes the IEV transmembrane phosphoprotein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377145.1,GeneID:72551558 + GENEPIO:0101691 protein name (MPOX) CPXV173 protein (MPOX) A protein name that denotes the CPXV173 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377146.1,GeneID:72551559 + GENEPIO:0101692 protein name (MPOX) hypothetical protein (MPOX) A protein name that denotes the hypothetical protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010415322.1,GeneID:72551560 + GENEPIO:0101693 protein name (MPOX) CD47-like protein (MPOX) A protein name that denotes the CD47-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377147.1,GeneID:72551561 + GENEPIO:0101694 protein name (MPOX) Profilin domain protein (MPOX) A protein name that denotes the Profilin domain protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377149.1,GeneID:72551563 + GENEPIO:0101695 protein name (MPOX) Type-I membrane glycoprotein (MPOX) A protein name that denotes the Type-I membrane glycoprotein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377150.1,GeneID:72551564 + GENEPIO:0101696 protein name (MPOX) MPXVgp154 protein (MPOX) A protein name that denotes the MPXVgp154 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377151.1,GeneID:72551565 + GENEPIO:0101697 protein name (MPOX) Hydroxysteroid dehydrogenase protein (MPOX) A protein name that denotes the Hydroxysteroid dehydrogenase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377152.1,GeneID:72551566 + GENEPIO:0101698 protein name (MPOX) Copper/zinc superoxide dismutase protein (MPOX) A protein name that denotes the Copper/zinc superoxide dismutase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377153.1,GeneID:72551567 + GENEPIO:0101699 protein name (MPOX) Thymidylate kinase protein (MPOX) A protein name that denotes the Thymidylate kinase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377155.1,GeneID:72551569 + GENEPIO:0101700 protein name (MPOX) DNA ligase (2) protein (MPOX) A protein name that denotes the DNA ligase (2) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377156.1,GeneID:72551570 + GENEPIO:0101701 protein name (MPOX) M137R protein (MPOX) A protein name that denotes the M137R protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377157.1,GeneID:72551571 + GENEPIO:0101702 protein name (MPOX) Hemagglutinin protein (MPOX) A protein name that denotes the Hemagglutinin protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377158.1,GeneID:72551572 + GENEPIO:0101703 protein name (MPOX) Ser/thr kinase protein (MPOX) A protein name that denotes the Ser/thr kinase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377159.1,GeneID:72551573 + GENEPIO:0101703 protein name (MPOX) Ser/thr kinase protein (MPOX) A protein name that denotes the Ser/thr kinase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377168.1,GeneID:72551582 + GENEPIO:0101704 protein name (MPOX) Schlafen (1) protein (MPOX) A protein name that denotes the Schlafen (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377160.1,GeneID:72551574 + GENEPIO:0101705 protein name (MPOX) EEV type-I membrane glycoprotein (MPOX) A protein name that denotes the EEV type-I membrane glycoprotein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377162.1,GeneID:72551576 + GENEPIO:0101706 protein name (MPOX) Ankyrin-like protein (46) (MPOX) A protein name that denotes the Ankyrin-like protein (46) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377163.1,GeneID:72551577 + GENEPIO:0101707 protein name (MPOX) Virulence protein (MPOX) A protein name that denotes the Virulence protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377164.1,GeneID:72551578 + GENEPIO:0101707 protein name (MPOX) Virulence protein (MPOX) A protein name that denotes the Virulence protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377175.1,GeneID:72551588 + GENEPIO:0101708 protein name (MPOX) Soluble interferon-gamma receptor-like protein (MPOX) A protein name that denotes the Soluble interferon-gamma receptor-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377165.1,GeneID:72551579 + GENEPIO:0101709 protein name (MPOX) Intracellular viral protein (MPOX) A protein name that denotes the Intracellular viral protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377166.1,GeneID:72551580 + GENEPIO:0101710 protein name (MPOX) CPXV205 protein (MPOX) A protein name that denotes the CPXV205 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377167.1,GeneID:72551581 + GENEPIO:0101711 protein name (MPOX) IFN-alpha/beta-receptor-like secreted glycoprotein (MPOX) A protein name that denotes the IFN-alpha/beta-receptor-like secreted glycoprotein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377172.1,GeneID:72551585 + GENEPIO:0101712 protein name (MPOX) Ankyrin repeat protein (44) (MPOX) A protein name that denotes the Ankyrin repeat protein (44) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377173.1,GeneID:72551586 + GENEPIO:0101713 protein name (MPOX) B22R family protein (MPOX) A protein name that denotes the B22R family protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377176.1,GeneID:72551589 + GENEPIO:0101714 protein name (MPOX) Brix domain protein (MPOX) A protein name that denotes the Brix domain protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377184.1,GeneID:72551591 + GENEPIO:0101720 protein symbol (MPOX) Opg001 protein (MPOX) A protein symbol that denotes the Chemokine binding protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377002.1,GeneID:72551607 + GENEPIO:0101720 protein symbol (MPOX) Opg001 protein (MPOX) A protein symbol that denotes the Chemokine binding protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377182.1,GeneID:72551595 + GENEPIO:0101721 protein symbol (MPOX) Opg002 protein (MPOX) A protein symbol that denotes the Crm-B secreted TNF-alpha-receptor-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377003.1,GeneID:72551418 + GENEPIO:0101721 protein symbol (MPOX) Opg002 protein (MPOX) A protein symbol that denotes the Crm-B secreted TNF-alpha-receptor-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377181.1,GeneID:72551594 + GENEPIO:0101722 protein symbol (MPOX) Opg003 protein (MPOX) A protein symbol that denotes the Ankyrin repeat protein (25) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377004.1,GeneID:72551419 + GENEPIO:0101722 protein symbol (MPOX) Opg003 protein (MPOX) A protein symbol that denotes the Ankyrin repeat protein (25) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377180.1,GeneID:72551593 + GENEPIO:0101723 protein symbol (MPOX) Opg015 protein (MPOX) A protein symbol that denotes the Ankyrin repeat protein (39) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377005.1,GeneID:72551420 + GENEPIO:0101723 protein symbol (MPOX) Opg015 protein (MPOX) A protein symbol that denotes the Ankyrin repeat protein (39) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377179.1,GeneID:72551592 + GENEPIO:0101724 protein symbol (MPOX) Opg019 protein (MPOX) A protein symbol that denotes the EGF-like domain protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377006.1,GeneID:72551421 + GENEPIO:0101725 protein symbol (MPOX) Opg021 protein (MPOX) A protein symbol that denotes the Zinc finger-like protein (2) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377007.1,GeneID:72551422 + GENEPIO:0101726 protein symbol (MPOX) Opg022 protein (MPOX) A protein symbol that denotes the Interleukin-18-binding protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377008.1,GeneID:72551423 + GENEPIO:0101727 protein symbol (MPOX) Opg023 protein (MPOX) A protein symbol that denotes the Ankyrin repeat protein (2) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377009.1,GeneID:72551424 + GENEPIO:0101728 protein symbol (MPOX) Opg024 protein (MPOX) A protein symbol that denotes the retroviral pseudoprotease-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377010.1,GeneID:72551425 + GENEPIO:0101729 protein symbol (MPOX) Opg025 protein (MPOX) A protein symbol that denotes the Ankyrin repeat protein (14) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377011.1,GeneID:72551426 + GENEPIO:0101730 protein symbol (MPOX) Opg027 protein (MPOX) A protein symbol that denotes the Host range protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377012.1,GeneID:72551427 + GENEPIO:0101731 protein symbol (MPOX) Opg029 protein (MPOX) A protein symbol that denotes the Bcl-2-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377013.1,GeneID:72551428 + GENEPIO:0101732 protein symbol (MPOX) Opg030 protein (MPOX) A protein symbol that denotes the Kelch-like protein (1) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377014.1,GeneID:72551429 + GENEPIO:0101733 protein symbol (MPOX) Opg031 protein (MPOX) A protein symbol that denotes the C4L/C10L-like family protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377015.1,GeneID:72551430 + GENEPIO:0101734 protein symbol (MPOX) Opg034 protein (MPOX) A protein symbol that denotes the Bcl-2-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377017.1,GeneID:72551431 + GENEPIO:0101735 protein symbol (MPOX) Opg035 protein (MPOX) A protein symbol that denotes the Bcl-2-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377018.1,GeneID:72551432 + GENEPIO:0101736 protein symbol (MPOX) Opg037 protein (MPOX) A protein symbol that denotes the Ankyrin-like protein (1) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377020.1,GeneID:72551434 + GENEPIO:0101737 protein symbol (MPOX) Opg038 protein (MPOX) A protein symbol that denotes the NFkB inhibitor protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377021.1,GeneID:72551435 + GENEPIO:0101738 protein symbol (MPOX) Opg039 protein (MPOX) A protein symbol that denotes the Ankyrin-like protein (3) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377022.1,GeneID:72551436 + GENEPIO:0101739 protein symbol (MPOX) Opg040 protein (MPOX) A protein symbol that denotes the Serpin protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377023.1,GeneID:72551437 + GENEPIO:0101740 protein symbol (MPOX) Opg042 protein (MPOX) A protein symbol that denotes the Phospholipase-D-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377025.1,GeneID:72551438 + GENEPIO:0101741 protein symbol (MPOX) Opg043 protein (MPOX) A protein symbol that denotes the Putative monoglyceride lipase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377026.1,GeneID:72551439 + GENEPIO:0101742 protein symbol (MPOX) Opg045 protein (MPOX) A protein symbol that denotes the Caspase-9 inhibitor protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377028.1,GeneID:72551441 + GENEPIO:0101743 protein symbol (MPOX) Opg046 protein (MPOX) A protein symbol that denotes the dUTPase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377029.1,GeneID:72551442 + GENEPIO:0101744 protein symbol (MPOX) Opg047 protein (MPOX) A protein symbol that denotes the Kelch-like protein (2) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377030.1,GeneID:72551443 + GENEPIO:0101745 protein symbol (MPOX) Opg048 protein (MPOX) A protein symbol that denotes the Ribonucleotide reductase small subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377031.1,GeneID:72551444 + GENEPIO:0101746 protein symbol (MPOX) Opg049 protein (MPOX) A protein symbol that denotes the Telomere-binding protein I6 (1) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377032.1,GeneID:72551445 + GENEPIO:0101747 protein symbol (MPOX) Opg050 protein (MPOX) A protein symbol that denotes the CPXV053 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377033.1,GeneID:72551446 + GENEPIO:0101748 protein symbol (MPOX) Opg051 protein (MPOX) A protein symbol that denotes the CPXV054 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377034.1,GeneID:72551447 + GENEPIO:0101749 protein symbol (MPOX) Opg052 protein (MPOX) A protein symbol that denotes the Cytoplasmic protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377035.1,GeneID:72551448 + GENEPIO:0101750 protein symbol (MPOX) Opg053 protein (MPOX) A protein symbol that denotes the IMV membrane protein L1R (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377036.1,GeneID:72551449 + GENEPIO:0101751 protein symbol (MPOX) Opg054 protein (MPOX) A protein symbol that denotes the Serine/threonine-protein kinase (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377037.1,GeneID:72551450 + GENEPIO:0101752 protein symbol (MPOX) Opg055 protein (MPOX) A protein symbol that denotes the Protein F11 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377038.1,GeneID:72551451 + GENEPIO:0101753 protein symbol (MPOX) Opg056 protein (MPOX) A protein symbol that denotes the EEV maturation protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377039.1,GeneID:72551452 + GENEPIO:0101754 protein symbol (MPOX) Opg057 protein (MPOX) A protein symbol that denotes the Palmytilated EEV membrane protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377040.1,GeneID:72551453 + GENEPIO:0101755 protein symbol (MPOX) Opg058 protein (MPOX) A protein symbol that denotes the Protein F14 (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377041.1,GeneID:72551454 + GENEPIO:0101756 protein symbol (MPOX) Opg059 protein (MPOX) A protein symbol that denotes the Cytochrome C oxidase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377042.1,GeneID:72551455 + GENEPIO:0101757 protein symbol (MPOX) Opg060 protein (MPOX) A protein symbol that denotes the Protein F15 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377043.1,GeneID:72551456 + GENEPIO:0101758 protein symbol (MPOX) Opg061 protein (MPOX) A protein symbol that denotes the Protein F16 (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377044.1,GeneID:72551457 + GENEPIO:0101759 protein symbol (MPOX) Opg062 protein (MPOX) A protein symbol that denotes the DNA-binding phosphoprotein (1) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377045.1,GeneID:72551458 + GENEPIO:0101760 protein symbol (MPOX) Opg063 protein (MPOX) A protein symbol that denotes the Poly(A) polymerase catalytic subunit (3) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377046.1,GeneID:72551459 + GENEPIO:0101761 protein symbol (MPOX) Opg064 protein (MPOX) A protein symbol that denotes the Iev morphogenesis protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377047.1,GeneID:72551460 + GENEPIO:0101762 protein symbol (MPOX) Opg065 protein (MPOX) A protein symbol that denotes the Double-stranded RNA binding protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377048.1,GeneID:72551461 + GENEPIO:0101763 protein symbol (MPOX) Opg066 protein (MPOX) A protein symbol that denotes the DNA-directed RNA polymerase 30 kDa polypeptide protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377049.1,GeneID:72551462 + GENEPIO:0101764 protein symbol (MPOX) Opg068 protein (MPOX) A protein symbol that denotes the IMV membrane protein E6 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377051.1,GeneID:72551463 + GENEPIO:0101765 protein symbol (MPOX) Opg069 protein (MPOX) A protein symbol that denotes the Myristoylated protein E7 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377052.1,GeneID:72551464 + GENEPIO:0101766 protein symbol (MPOX) Opg070 protein (MPOX) A protein symbol that denotes the Membrane protein E8 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377053.1,GeneID:72551465 + GENEPIO:0101767 protein symbol (MPOX) Opg071 protein (MPOX) A protein symbol that denotes the DNA polymerase (2) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377054.1,GeneID:72551466 + GENEPIO:0101768 protein symbol (MPOX) Opg072 protein (MPOX) A protein symbol that denotes the Sulfhydryl oxidase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377055.1,GeneID:72551467 + GENEPIO:0101769 protein symbol (MPOX) Opg073 protein (MPOX) A protein symbol that denotes the Virion core protein E11 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377056.1,GeneID:72551468 + GENEPIO:0101770 protein symbol (MPOX) Opg074 protein (MPOX) A protein symbol that denotes the Iev morphogenesis protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377057.1,GeneID:72551469 + GENEPIO:0101771 protein symbol (MPOX) Opg075 protein (MPOX) A protein symbol that denotes the Glutaredoxin-1 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377058.1,GeneID:72551470 + GENEPIO:0101772 protein symbol (MPOX) Opg077 protein (MPOX) A protein symbol that denotes the Telomere-binding protein I1 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377059.1,GeneID:72551472 + GENEPIO:0101773 protein symbol (MPOX) Opg078 protein (MPOX) A protein symbol that denotes the IMV membrane protein I2 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377060.1,GeneID:72551473 + GENEPIO:0101774 protein symbol (MPOX) Opg079 protein (MPOX) A protein symbol that denotes the DNA-binding phosphoprotein (2) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377061.1,GeneID:72551474 + GENEPIO:0101775 protein symbol (MPOX) Opg080 protein (MPOX) A protein symbol that denotes the Ribonucleoside-diphosphate reductase (2) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377062.1,GeneID:72551475 + GENEPIO:0101776 protein symbol (MPOX) Opg081 protein (MPOX) A protein symbol that denotes the IMV membrane protein I5 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377063.1,GeneID:72551476 + GENEPIO:0101777 protein symbol (MPOX) Opg082 protein (MPOX) A protein symbol that denotes the Telomere-binding protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377064.1,GeneID:72551477 + GENEPIO:0101778 protein symbol (MPOX) Opg083 protein (MPOX) A protein symbol that denotes the Viral core cysteine proteinase (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377065.1,GeneID:72551478 + GENEPIO:0101779 protein symbol (MPOX) Opg084 protein (MPOX) A protein symbol that denotes the RNA helicase NPH-II (2) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377066.1,GeneID:72551479 + GENEPIO:0101780 protein symbol (MPOX) Opg085 protein (MPOX) A protein symbol that denotes the Metalloendopeptidase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377067.1,GeneID:72551480 + GENEPIO:0101781 protein symbol (MPOX) Opg086 protein (MPOX) A protein symbol that denotes the Entry/fusion complex component protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377068.1,GeneID:72551481 + GENEPIO:0101782 protein symbol (MPOX) Opg087 protein (MPOX) A protein symbol that denotes the Late transcription elongation factor protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377069.1,GeneID:72551482 + GENEPIO:0101783 protein symbol (MPOX) Opg088 protein (MPOX) A protein symbol that denotes the Glutaredoxin-2 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377070.1,GeneID:72551483 + GENEPIO:0101784 protein symbol (MPOX) Opg089 protein (MPOX) A protein symbol that denotes the FEN1-like nuclease protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377071.1,GeneID:72551484 + GENEPIO:0101785 protein symbol (MPOX) Opg090 protein (MPOX) A protein symbol that denotes the DNA-directed RNA polymerase 7 kDa subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377072.1,GeneID:72551485 + GENEPIO:0101786 protein symbol (MPOX) Opg091 protein (MPOX) A protein symbol that denotes the Nlpc/p60 superfamily protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377073.1,GeneID:72551486 + GENEPIO:0101787 protein symbol (MPOX) Opg092 protein (MPOX) A protein symbol that denotes the Assembly protein G7 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377074.1,GeneID:72551487 + GENEPIO:0101788 protein symbol (MPOX) Opg093 protein (MPOX) A protein symbol that denotes the Late transcription factor VLTF-1 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377075.1,GeneID:72551488 + GENEPIO:0101789 protein symbol (MPOX) Opg094 protein (MPOX) A protein symbol that denotes the Myristylated protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377076.1,GeneID:72551489 + GENEPIO:0101790 protein symbol (MPOX) Opg095 protein (MPOX) A protein symbol that denotes the IMV membrane protein L1R (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377077.1,GeneID:72551490 + GENEPIO:0101791 protein symbol (MPOX) Opg096 protein (MPOX) A protein symbol that denotes the Crescent membrane and immature virion formation protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377078.1,GeneID:72551491 + GENEPIO:0101792 protein symbol (MPOX) Opg097 protein (MPOX) A protein symbol that denotes the Internal virion L3/FP4 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377079.1,GeneID:72551492 + GENEPIO:0101793 protein symbol (MPOX) Opg098 protein (MPOX) A protein symbol that denotes the Nucleic acid binding protein VP8/L4R (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377080.1,GeneID:72551493 + GENEPIO:0101794 protein symbol (MPOX) Opg099 protein (MPOX) A protein symbol that denotes the Membrane protein CL5 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377081.1,GeneID:72551494 + GENEPIO:0101795 protein symbol (MPOX) Opg100 protein (MPOX) A protein symbol that denotes the IMV membrane protein J1 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377082.1,GeneID:72551495 + GENEPIO:0101796 protein symbol (MPOX) Opg101 protein (MPOX) A protein symbol that denotes the Thymidine kinase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377083.1,GeneID:72551496 + GENEPIO:0101797 protein symbol (MPOX) Opg102 protein (MPOX) A protein symbol that denotes the Cap-specific mRNA protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377084.1,GeneID:72551497 + GENEPIO:0101798 protein symbol (MPOX) Opg103 protein (MPOX) A protein symbol that denotes the DNA-directed RNA polymerase subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377085.1,GeneID:72551498 + GENEPIO:0101799 protein symbol (MPOX) Opg104 protein (MPOX) A protein symbol that denotes the Myristylated protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377086.1,GeneID:72551499 + GENEPIO:0101800 protein symbol (MPOX) Opg105 protein (MPOX) A protein symbol that denotes the DNA-dependent RNA polymerase subunit rpo147 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377087.1,GeneID:72551500 + GENEPIO:0101801 protein symbol (MPOX) Opg106 protein (MPOX) A protein symbol that denotes the Tyr/ser protein phosphatase (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377088.1,GeneID:72551501 + GENEPIO:0101802 protein symbol (MPOX) Opg107 protein (MPOX) A protein symbol that denotes the Entry-fusion complex essential component protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377089.1,GeneID:72551502 + GENEPIO:0101803 protein symbol (MPOX) Opg108 protein (MPOX) A protein symbol that denotes the IMV heparin binding surface protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377090.1,GeneID:72551503 + GENEPIO:0101804 protein symbol (MPOX) Opg109 protein (MPOX) A protein symbol that denotes the RNA polymerase-associated transcription-specificity factor RAP94 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377091.1,GeneID:72551504 + GENEPIO:0101805 protein symbol (MPOX) Opg110 protein (MPOX) A protein symbol that denotes the Late transcription factor VLTF-4 (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377092.1,GeneID:72551505 + GENEPIO:0101806 protein symbol (MPOX) Opg111 protein (MPOX) A protein symbol that denotes the DNA topoisomerase type I protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377093.1,GeneID:72551506 + GENEPIO:0101807 protein symbol (MPOX) Opg112 protein (MPOX) A protein symbol that denotes the Late protein H7 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377094.1,GeneID:72551507 + GENEPIO:0101808 protein symbol (MPOX) Opg113 protein (MPOX) A protein symbol that denotes the mRNA capping enzyme large subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377095.1,GeneID:72551508 + GENEPIO:0101809 protein symbol (MPOX) Opg114 protein (MPOX) A protein symbol that denotes the Virion protein D2 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377096.1,GeneID:72551509 + GENEPIO:0101810 protein symbol (MPOX) Opg115 protein (MPOX) A protein symbol that denotes the Virion core protein D3 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377097.1,GeneID:72551510 + GENEPIO:0101811 protein symbol (MPOX) Opg116 protein (MPOX) A protein symbol that denotes the Uracil DNA glycosylase superfamily protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377098.1,GeneID:72551511 + GENEPIO:0101812 protein symbol (MPOX) Opg117 protein (MPOX) A protein symbol that denotes the NTPase (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377099.1,GeneID:72551512 + GENEPIO:0101813 protein symbol (MPOX) Opg118 protein (MPOX) A protein symbol that denotes the Early transcription factor 70 kDa subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377100.1,GeneID:72551513 + GENEPIO:0101814 protein symbol (MPOX) Opg119 protein (MPOX) A protein symbol that denotes the RNA polymerase subunit RPO18 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377101.1,GeneID:72551514 + GENEPIO:0101815 protein symbol (MPOX) Opg120 protein (MPOX) A protein symbol that denotes the Carbonic anhydrase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377102.1,GeneID:72551515 + GENEPIO:0101816 protein symbol (MPOX) Opg121 protein (MPOX) A protein symbol that denotes the NUDIX domain protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377103.1,GeneID:72551516 + GENEPIO:0101817 protein symbol (MPOX) Opg122 protein (MPOX) A protein symbol that denotes the MutT motif protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377104.1,GeneID:72551517 + GENEPIO:0101818 protein symbol (MPOX) Opg123 protein (MPOX) A protein symbol that denotes the Nucleoside triphosphatase I protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377105.1,GeneID:72551518 + GENEPIO:0101819 protein symbol (MPOX) Opg124 protein (MPOX) A protein symbol that denotes the mRNA capping enzyme small subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377106.1,GeneID:72551519 + GENEPIO:0101820 protein symbol (MPOX) Opg125 protein (MPOX) A protein symbol that denotes the Rifampicin resistance protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377107.1,GeneID:72551520 + GENEPIO:0101821 protein symbol (MPOX) Opg126 protein (MPOX) A protein symbol that denotes the Late transcription factor VLTF-2 (2) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377108.1,GeneID:72551521 + GENEPIO:0101822 protein symbol (MPOX) Opg127 protein (MPOX) A protein symbol that denotes the Late transcription factor VLTF-3 (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377109.1,GeneID:72551522 + GENEPIO:0101823 protein symbol (MPOX) Opg128 protein (MPOX) A protein symbol that denotes the S-S bond formation pathway protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377110.1,GeneID:72551523 + GENEPIO:0101824 protein symbol (MPOX) Opg129 protein (MPOX) A protein symbol that denotes the Virion core protein P4b (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377111.1,GeneID:72551524 + GENEPIO:0101825 protein symbol (MPOX) Opg130 protein (MPOX) A protein symbol that denotes the A5L protein-like (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377112.1,GeneID:72551525 + GENEPIO:0101826 protein symbol (MPOX) Opg131 protein (MPOX) A protein symbol that denotes the DNA-directed RNA polymerase 19 kDa subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377113.1,GeneID:72551526 + GENEPIO:0101827 protein symbol (MPOX) Opg132 protein (MPOX) A protein symbol that denotes the Virion morphogenesis protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377114.1,GeneID:72551527 + GENEPIO:0101828 protein symbol (MPOX) Opg133 protein (MPOX) A protein symbol that denotes the Early transcription factor 82 kDa subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377115.1,GeneID:72551528 + GENEPIO:0101829 protein symbol (MPOX) Opg134 protein (MPOX) A protein symbol that denotes the Intermediate transcription factor VITF-3 (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377116.1,GeneID:72551529 + GENEPIO:0101830 protein symbol (MPOX) Opg135 protein (MPOX) A protein symbol that denotes the IMV membrane protein A9 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377117.1,GeneID:72551530 + GENEPIO:0101831 protein symbol (MPOX) Opg136 protein (MPOX) A protein symbol that denotes the Virion core protein P4a (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377118.1,GeneID:72551531 + GENEPIO:0101832 protein symbol (MPOX) Opg137 protein (MPOX) A protein symbol that denotes the Viral membrane formation protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377119.1,GeneID:72551532 + GENEPIO:0101833 protein symbol (MPOX) Opg138 protein (MPOX) A protein symbol that denotes the A12 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377120.1,GeneID:72551533 + GENEPIO:0101834 protein symbol (MPOX) Opg139 protein (MPOX) A protein symbol that denotes the IMV membrane protein A13L (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377121.1,GeneID:72551534 + GENEPIO:0101835 protein symbol (MPOX) Opg140 protein (MPOX) A protein symbol that denotes the IMV membrane protein A14 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377122.1,GeneID:72551535 + GENEPIO:0101836 protein symbol (MPOX) Opg141 protein (MPOX) A protein symbol that denotes the DUF1029 domain protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377123.1,GeneID:72551536 + GENEPIO:0101837 protein symbol (MPOX) Opg142 protein (MPOX) A protein symbol that denotes the Core protein A15 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377124.1,GeneID:72551537 + GENEPIO:0101838 protein symbol (MPOX) Opg143 protein (MPOX) A protein symbol that denotes the Myristylated protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377125.1,GeneID:72551538 + GENEPIO:0101839 protein symbol (MPOX) Opg144 protein (MPOX) A protein symbol that denotes the IMV membrane protein P21 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377126.1,GeneID:72551539 + GENEPIO:0101840 protein symbol (MPOX) Opg145 protein (MPOX) A protein symbol that denotes the DNA helicase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377127.1,GeneID:72551540 + GENEPIO:0101841 protein symbol (MPOX) Opg146 protein (MPOX) A protein symbol that denotes the Zinc finger-like protein (1) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377128.1,GeneID:72551541 + GENEPIO:0101842 protein symbol (MPOX) Opg147 protein (MPOX) A protein symbol that denotes the IMV membrane protein A21 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377129.1,GeneID:72551542 + GENEPIO:0101843 protein symbol (MPOX) Opg148 protein (MPOX) A protein symbol that denotes the DNA polymerase processivity factor protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377130.1,GeneID:72551543 + GENEPIO:0101844 protein symbol (MPOX) Opg149 protein (MPOX) A protein symbol that denotes the Holliday junction resolvase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377131.1,GeneID:72551544 + GENEPIO:0101845 protein symbol (MPOX) Opg150 protein (MPOX) A protein symbol that denotes the Intermediate transcription factor VITF-3 (2) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377132.1,GeneID:72551545 + GENEPIO:0101846 protein symbol (MPOX) Opg151 protein (MPOX) A protein symbol that denotes the DNA-dependent RNA polymerase subunit rpo132 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377133.1,GeneID:72551546 + GENEPIO:0101847 protein symbol (MPOX) Opg153 protein (MPOX) A protein symbol that denotes the Orthopoxvirus A26L/A30L protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377134.1,GeneID:72551547 + GENEPIO:0101848 protein symbol (MPOX) Opg154 protein (MPOX) A protein symbol that denotes the IMV surface fusion protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377135.1,GeneID:72551548 + GENEPIO:0101849 protein symbol (MPOX) Opg155 protein (MPOX) A protein symbol that denotes the Envelope protein A28 homolog (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377136.1,GeneID:72551549 + GENEPIO:0101850 protein symbol (MPOX) Opg156 protein (MPOX) A protein symbol that denotes the DNA-directed RNA polymerase 35 kDa subunit protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377137.1,GeneID:72551550 + GENEPIO:0101851 protein symbol (MPOX) Opg157 protein (MPOX) A protein symbol that denotes the IMV membrane protein A30 (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377138.1,GeneID:72551551 + GENEPIO:0101852 protein symbol (MPOX) Opg158 protein (MPOX) A protein symbol that denotes the A32.5L protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377139.1,GeneID:72551552 + GENEPIO:0101853 protein symbol (MPOX) Opg159 protein (MPOX) A protein symbol that denotes the CPXV166 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377140.1,GeneID:72551553 + GENEPIO:0101854 protein symbol (MPOX) Opg160 protein (MPOX) A protein symbol that denotes the ATPase A32 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377141.1,GeneID:72551554 + GENEPIO:0101855 protein symbol (MPOX) Opg161 protein (MPOX) A protein symbol that denotes the EEV glycoprotein (1) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377142.1,GeneID:72551555 + GENEPIO:0101856 protein symbol (MPOX) Opg162 protein (MPOX) A protein symbol that denotes the EEV glycoprotein (2) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377143.1,GeneID:72551556 + GENEPIO:0101857 protein symbol (MPOX) Opg163 protein (MPOX) A protein symbol that denotes the MHC class II antigen presentation inhibitor protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377144.1,GeneID:72551557 + GENEPIO:0101858 protein symbol (MPOX) Opg164 protein (MPOX) A protein symbol that denotes the IEV transmembrane phosphoprotein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377145.1,GeneID:72551558 + GENEPIO:0101859 protein symbol (MPOX) Opg165 protein (MPOX) A protein symbol that denotes the CPXV173 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377146.1,GeneID:72551559 + GENEPIO:0101860 protein symbol (MPOX) Opg166 protein (MPOX) A protein symbol that denotes the hypothetical protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010415322.1,GeneID:72551560 + GENEPIO:0101861 protein symbol (MPOX) Opg167 protein (MPOX) A protein symbol that denotes the CD47-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377147.1,GeneID:72551561 + GENEPIO:0101862 protein symbol (MPOX) Opg170 protein (MPOX) A protein symbol that denotes the Chemokine binding protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377148.1,GeneID:72551562 + GENEPIO:0101863 protein symbol (MPOX) Opg171 protein (MPOX) A protein symbol that denotes the Profilin domain protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377149.1,GeneID:72551563 + GENEPIO:0101864 protein symbol (MPOX) Opg172 protein (MPOX) A protein symbol that denotes the Type-I membrane glycoprotein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377150.1,GeneID:72551564 + GENEPIO:0101865 protein symbol (MPOX) Opg173 protein (MPOX) A protein symbol that denotes the MPXVgp154 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377151.1,GeneID:72551565 + GENEPIO:0101866 protein symbol (MPOX) Opg174 protein (MPOX) A protein symbol that denotes the Hydroxysteroid dehydrogenase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377152.1,GeneID:72551566 + GENEPIO:0101867 protein symbol (MPOX) Opg175 protein (MPOX) A protein symbol that denotes the Copper/zinc superoxide dismutase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377153.1,GeneID:72551567 + GENEPIO:0101868 protein symbol (MPOX) Opg176 protein (MPOX) A protein symbol that denotes the Bcl-2-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377154.1,GeneID:72551568 + GENEPIO:0101869 protein symbol (MPOX) Opg178 protein (MPOX) A protein symbol that denotes the Thymidylate kinase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377155.1,GeneID:72551569 + GENEPIO:0101870 protein symbol (MPOX) Opg180 protein (MPOX) A protein symbol that denotes the DNA ligase (2) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377156.1,GeneID:72551570 + GENEPIO:0101871 protein symbol (MPOX) Opg181 protein (MPOX) A protein symbol that denotes the M137R protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377157.1,GeneID:72551571 + GENEPIO:0101872 protein symbol (MPOX) Opg185 protein (MPOX) A protein symbol that denotes the Hemagglutinin protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377158.1,GeneID:72551572 + GENEPIO:0101873 protein symbol (MPOX) Opg187 protein (MPOX) A protein symbol that denotes the Ser/thr kinase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377159.1,GeneID:72551573 + GENEPIO:0101874 protein symbol (MPOX) Opg188 protein (MPOX) A protein symbol that denotes the Schlafen (1) protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377160.1,GeneID:72551574 + GENEPIO:0101875 protein symbol (MPOX) Opg189 protein (MPOX) A protein symbol that denotes the Ankyrin repeat protein (25) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377161.1,GeneID:72551575 + GENEPIO:0101876 protein symbol (MPOX) Opg190 protein (MPOX) A protein symbol that denotes the EEV type-I membrane glycoprotein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377162.1,GeneID:72551576 + GENEPIO:0101877 protein symbol (MPOX) Opg191 protein (MPOX) A protein symbol that denotes the Ankyrin-like protein (46) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377163.1,GeneID:72551577 + GENEPIO:0101878 protein symbol (MPOX) Opg192 protein (MPOX) A protein symbol that denotes the Virulence protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377164.1,GeneID:72551578 + GENEPIO:0101879 protein symbol (MPOX) Opg193 protein (MPOX) A protein symbol that denotes the Soluble interferon-gamma receptor-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377165.1,GeneID:72551579 + GENEPIO:0101880 protein symbol (MPOX) Opg195 protein (MPOX) A protein symbol that denotes the Intracellular viral protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377166.1,GeneID:72551580 + GENEPIO:0101881 protein symbol (MPOX) Opg197 protein (MPOX) A protein symbol that denotes the CPXV205 protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377167.1,GeneID:72551581 + GENEPIO:0101882 protein symbol (MPOX) Opg198 protein (MPOX) A protein symbol that denotes the Ser/thr kinase protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377168.1,GeneID:72551582 + GENEPIO:0101883 protein symbol (MPOX) Opg199 protein (MPOX) A protein symbol that denotes the Serpin protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377169.1,GeneID:72551583 + GENEPIO:0101884 protein symbol (MPOX) Opg200 protein (MPOX) A protein symbol that denotes the Bcl-2-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377170.1,GeneID:72551584 + GENEPIO:0101885 protein symbol (MPOX) Opg204 protein (MPOX) A protein symbol that denotes the IFN-alpha/beta-receptor-like secreted glycoprotein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377172.1,GeneID:72551585 + GENEPIO:0101886 protein symbol (MPOX) Opg205 protein (MPOX) A protein symbol that denotes the Ankyrin repeat protein (44) (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377173.1,GeneID:72551586 + GENEPIO:0101887 protein symbol (MPOX) Opg208 protein (MPOX) A protein symbol that denotes the Serpin protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377174.1,GeneID:72551587 + GENEPIO:0101888 protein symbol (MPOX) Opg209 protein (MPOX) A protein symbol that denotes the Virulence protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377175.1,GeneID:72551588 + GENEPIO:0101889 protein symbol (MPOX) Opg210 protein (MPOX) A protein symbol that denotes the B22R family protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377176.1,GeneID:72551589 + GENEPIO:0101890 protein symbol (MPOX) Opg005 protein (MPOX) A protein symbol that denotes the Bcl-2-like protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377177.1,GeneID:72551590 + GENEPIO:0101891 protein symbol (MPOX) Opg016 protein (MPOX) A protein symbol that denotes the Brix domain protein (MPOX). Instance 2024-09-02T20:03:59.988Z https://orcid.org/0000-0002-0548-891X GenBank:YP_010377184.1,GeneID:72551591 From bd967d566ccf4cc9114f659f0239c38255bb3fbe Mon Sep 17 00:00:00 2001 From: miseminger Date: Fri, 27 Sep 2024 15:22:54 -0700 Subject: [PATCH 041/161] update for MPOX --- bin/robot2json.py | 59 +++++++++++++++++++++++++++++++++-------------- 1 file changed, 42 insertions(+), 17 deletions(-) diff --git a/bin/robot2json.py b/bin/robot2json.py index f1bbcbd4..74bdf868 100644 --- a/bin/robot2json.py +++ b/bin/robot2json.py @@ -1,7 +1,8 @@ # temporary code for making JSON files out of ROBOT tables # ROBOT table: -# example run: +# example runs: # python robot2json.py --robot "/home/madeline/Downloads/VIRUS-MVP GENEPIO_ROBOT Tables - sc2_gene_protein_data.tsv" --ontology_genes '/home/madeline/Desktop/git_temp/nf-ncov-voc/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_genes.json' --ontology_proteins '/home/madeline/Desktop/git_temp/nf-ncov-voc/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_proteins.json' +# python robot2json.py --robot ~/Desktop/git_temp/nf-ncov-voc/assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ROBOT.tsv --ontology_genes '/home/madeline/Desktop/git_temp/nf-ncov-voc/assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ontology_genes.json' --ontology_proteins '/home/madeline/Desktop/git_temp/nf-ncov-voc/assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ontology_proteins.json' # remove orf1a gene name and symbol from TSV as they aren't used in the existing JSON import pandas as pd @@ -30,52 +31,74 @@ def parse_args(): proteins_file_path = args.ontology_proteins # load ROBOT file - sars = pd.read_csv(robot_path, header=0, sep='\t', usecols=['JSON_match', 'Ontology ID', 'parent class', 'label', 'is about', 'is about label']) + sars = pd.read_csv(robot_path, header=0, sep='\t', usecols=['Dbxref', 'Ontology ID', 'parent class', 'label']) # process genes - gene_names = sars[sars['parent class'].str.contains("gene name")] + gene_names = sars[sars['parent class'].str.contains("gene name")].copy(deep=True) gene_names['gene_name'] = gene_names['label'] gene_names['gene_name_id'] = gene_names['Ontology ID'] - gene_names['Dbxref'] = gene_names['JSON_match'].str.replace("GeneID", "NCBIGene") - gene_names = gene_names[['Dbxref', 'gene_name', 'gene_name_id', 'is about label']] + gene_names['Dbxref'] = gene_names['Dbxref'].str.replace("GeneID", "NCBIGene") #'JSON_match' + gene_names = gene_names[['Dbxref', 'gene_name', 'gene_name_id']] + gene_names.to_csv("GENE_NAMES_HAVOC.tsv", sep='\t', header=True, index=False) - gene_symbols = sars[sars['parent class'].str.contains("gene symbol")] + gene_symbols = sars[sars['parent class'].str.contains("gene symbol")].copy(deep=True) gene_symbols['gene_symbol'] = gene_symbols['label'] gene_symbols['gene_symbol_id'] = gene_symbols['Ontology ID'] - gene_symbols = gene_symbols[['gene_symbol', 'gene_symbol_id', 'is about label']] + gene_symbols = gene_symbols[['Dbxref', 'gene_symbol', 'gene_symbol_id']] + gene_symbols['Dbxref'] = gene_symbols['Dbxref'].str.replace("GeneID", "NCBIGene") #'JSON_match' + gene_symbols.to_csv("GENE_SYMBOLS_HAVOC.tsv", sep='\t', header=True, index=False) - genes = pd.merge(gene_names, gene_symbols, on='is about label', how='left') + genes = pd.merge(gene_names, gene_symbols, on='Dbxref', how='left') + + # add strand orientation + genes['strand_orientation'] = "sense strand orientation" + genes['strand_orientation_id'] = "GENEPIO:0700002" + + # add gene orientation + genes['gene_orientation'] = "forward gene orientation" + genes['gene_orientation_id'] = "GENEPIO:0700004" + reverse_gene_ids = ["NCBIGene:72551595", "NCBIGene:72551594", "NCBIGene:72551593", "NCBIGene:72551592"] + #print(genes[genes['gene_symbol'].duplicated(keep=False)]) #show which genes are duplicated + genes.loc[genes["Dbxref"].isin(reverse_gene_ids), 'gene_orientation'] = "reverse gene orientation" + genes.loc[genes["Dbxref"].isin(reverse_gene_ids), 'gene_orientation_id'] = "GENEPIO:0700005" + + genes.to_csv("GENES_HAVOC.tsv", sep='\t', header=True, index=False) # Define a custom function to create a nested structure + # ncbigene and the gene name are all the same, this is causing HAVOC def custom_nested_structure_genes(row): - return {row['Dbxref']: {'type': 'gene', 'Dbxref': row['Dbxref'], 'gene_name': {'label': row['gene_name'], 'uri': row['gene_name_id']}, 'gene_symbol': {'label': row['gene_symbol'], 'uri': row['gene_symbol_id']}}} + return {row['Dbxref']: {'type': 'gene', 'Dbxref': row['Dbxref'], 'gene_name': {'label': row['gene_name'], 'uri': row['gene_name_id']}, 'gene_symbol': {'label': row['gene_symbol'], 'uri': row['gene_symbol_id']}, 'gene_orientation': {'label': row['gene_orientation'], 'uri': row['gene_orientation_id']}}} # Apply the custom function to each row of the DataFrame json_data_custom = genes.apply(custom_nested_structure_genes, axis=1).tolist() # saves a list of dicts - json_data = {k: v for d in json_data_custom for k, v in d.items()} # transform to a single dict + json_data = {k:v for d in json_data_custom for k, v in d.items()} # transform to a single dict # Convert the dictionary of features to a JSON string json_str = json.dumps(json_data, indent=4) + #print(json_str) # Write the JSON string to a file with open(genes_file_path, "w") as genes_json_file: genes_json_file.write(json_str) + print("Gene terms saved as " + genes_file_path) + # now do proteins - protein_names = sars[sars['parent class'].str.contains("protein name")] + protein_names = sars[sars['parent class'].str.contains("protein name")].copy(deep=True) protein_names['protein_name'] = protein_names['label'] protein_names['protein_name_id'] = protein_names['Ontology ID'] - protein_names['protein_id'] = protein_names['JSON_match'] - protein_names = protein_names[['protein_id', 'protein_name', 'protein_name_id', 'is about label']] + protein_names['protein_id'] = protein_names['Dbxref'].str.split(pat=",", expand=True)[0].str.split(":", expand=True)[1] # extract eg. "YP_010377182.1" from "GenBank:YP_010377182.1,GeneID:72551595" + protein_names = protein_names[['protein_id', 'protein_name', 'protein_name_id']] - protein_symbols = sars[sars['parent class'].str.contains("protein symbol")] + protein_symbols = sars[sars['parent class'].str.contains("protein symbol")].copy(deep=True) protein_symbols['protein_symbol'] = protein_symbols['label'] protein_symbols['protein_symbol_id'] = protein_symbols['Ontology ID'] - protein_symbols = protein_symbols[['protein_symbol', 'protein_symbol_id', 'is about label']] + protein_symbols['protein_id'] = protein_symbols['Dbxref'].str.split(pat=",", expand=True)[0].str.split(":", expand=True)[1] # extract eg. "YP_010377182.1" from "GenBank:YP_010377182.1,GeneID:72551595" + protein_symbols = protein_symbols[['protein_id', 'protein_symbol', 'protein_symbol_id']] - proteins = pd.merge(protein_names, protein_symbols, on='is about label', how='left') + proteins = pd.merge(protein_names, protein_symbols, on='protein_id', how='left') # Define a custom function to create a nested structure def custom_nested_structure_proteins(row): @@ -90,4 +113,6 @@ def custom_nested_structure_proteins(row): # Write the JSON string to a file with open(proteins_file_path, "w") as protein_json_file: - protein_json_file.write(json_str) \ No newline at end of file + protein_json_file.write(json_str) + + print("Protein terms saved as " + proteins_file_path) \ No newline at end of file From fba32a95e335b868b01d4a9af3ddfaca53936ab3 Mon Sep 17 00:00:00 2001 From: miseminger Date: Fri, 27 Sep 2024 15:24:51 -0700 Subject: [PATCH 042/161] Add ontology term JSONs for MPOX --- .../NC_063383.1_ontology_genes.json | 2818 +++++++++++++++++ .../NC_063383.1_ontology_proteins.json | 2114 +++++++++++++ 2 files changed, 4932 insertions(+) create mode 100644 assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ontology_genes.json create mode 100644 assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ontology_proteins.json diff --git a/assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ontology_genes.json b/assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ontology_genes.json new file mode 100644 index 00000000..58f2f08b --- /dev/null +++ b/assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ontology_genes.json @@ -0,0 +1,2818 @@ +{ + "NCBIGene:72551607": { + "type": "gene", + "Dbxref": "NCBIGene:72551607", + "gene_name": { + "label": "orthopoxvirus gene 001 (MPOX)", + "uri": "GENEPIO:0101207" + }, + "gene_symbol": { + "label": "opg001 gene (MPOX)", + "uri": "GENEPIO:0101382" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551595": { + "type": "gene", + "Dbxref": "NCBIGene:72551595", + "gene_name": { + "label": "orthopoxvirus gene 001 (MPOX)", + "uri": "GENEPIO:0101207" + }, + "gene_symbol": { + "label": "opg001 gene (MPOX)", + "uri": "GENEPIO:0101382" + }, + "gene_orientation": { + "label": "reverse gene orientation", + "uri": "GENEPIO:0700005" + } + }, + "NCBIGene:72551418": { + "type": "gene", + "Dbxref": "NCBIGene:72551418", + "gene_name": { + "label": "orthopoxvirus gene 002 (MPOX)", + "uri": "GENEPIO:0101208" + }, + "gene_symbol": { + "label": "opg002 gene (MPOX)", + "uri": "GENEPIO:0101383" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551594": { + "type": "gene", + "Dbxref": "NCBIGene:72551594", + "gene_name": { + "label": "orthopoxvirus gene 002 (MPOX)", + "uri": "GENEPIO:0101208" + }, + "gene_symbol": { + "label": "opg002 gene (MPOX)", + "uri": "GENEPIO:0101383" + }, + "gene_orientation": { + "label": "reverse gene orientation", + "uri": "GENEPIO:0700005" + } + }, + "NCBIGene:72551419": { + "type": "gene", + "Dbxref": "NCBIGene:72551419", + "gene_name": { + "label": "orthopoxvirus gene 003 (MPOX)", + "uri": "GENEPIO:0101209" + }, + "gene_symbol": { + "label": "opg003 gene (MPOX)", + "uri": "GENEPIO:0101384" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551593": { + "type": "gene", + "Dbxref": "NCBIGene:72551593", + "gene_name": { + "label": "orthopoxvirus gene 003 (MPOX)", + "uri": "GENEPIO:0101209" + }, + "gene_symbol": { + "label": "opg003 gene (MPOX)", + "uri": "GENEPIO:0101384" + }, + "gene_orientation": { + "label": "reverse gene orientation", + "uri": "GENEPIO:0700005" + } + }, + "NCBIGene:72551420": { + "type": "gene", + "Dbxref": "NCBIGene:72551420", + "gene_name": { + "label": "orthopoxvirus gene 015 (MPOX)", + "uri": "GENEPIO:0101210" + }, + "gene_symbol": { + "label": "opg015 gene (MPOX)", + "uri": "GENEPIO:0101385" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551592": { + "type": "gene", + "Dbxref": "NCBIGene:72551592", + "gene_name": { + "label": "orthopoxvirus gene 015 (MPOX)", + "uri": "GENEPIO:0101210" + }, + "gene_symbol": { + "label": "opg015 gene (MPOX)", + "uri": "GENEPIO:0101385" + }, + "gene_orientation": { + "label": "reverse gene orientation", + "uri": "GENEPIO:0700005" + } + }, + "NCBIGene:72551421": { + "type": "gene", + "Dbxref": "NCBIGene:72551421", + "gene_name": { + "label": "orthopoxvirus gene 019 (MPOX)", + "uri": "GENEPIO:0101211" + }, + "gene_symbol": { + "label": "opg019 gene (MPOX)", + "uri": "GENEPIO:0101386" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551422": { + "type": "gene", + "Dbxref": "NCBIGene:72551422", + "gene_name": { + "label": "orthopoxvirus gene 021 (MPOX)", + "uri": "GENEPIO:0101212" + }, + "gene_symbol": { + "label": "opg021 gene (MPOX)", + "uri": "GENEPIO:0101387" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551423": { + "type": "gene", + "Dbxref": "NCBIGene:72551423", + "gene_name": { + "label": "orthopoxvirus gene 022 (MPOX)", + "uri": "GENEPIO:0101213" + }, + "gene_symbol": { + "label": "opg022 gene (MPOX)", + "uri": "GENEPIO:0101388" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551424": { + "type": "gene", + "Dbxref": "NCBIGene:72551424", + "gene_name": { + "label": "orthopoxvirus gene 023 (MPOX)", + "uri": "GENEPIO:0101214" + }, + "gene_symbol": { + "label": "opg023 gene (MPOX)", + "uri": "GENEPIO:0101389" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551425": { + "type": "gene", + "Dbxref": "NCBIGene:72551425", + "gene_name": { + "label": "orthopoxvirus gene 024 (MPOX)", + "uri": "GENEPIO:0101215" + }, + "gene_symbol": { + "label": "opg024 gene (MPOX)", + "uri": "GENEPIO:0101390" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551426": { + "type": "gene", + "Dbxref": "NCBIGene:72551426", + "gene_name": { + "label": "orthopoxvirus gene 025 (MPOX)", + "uri": "GENEPIO:0101216" + }, + "gene_symbol": { + "label": "opg025 gene (MPOX)", + "uri": "GENEPIO:0101391" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551427": { + "type": "gene", + "Dbxref": "NCBIGene:72551427", + "gene_name": { + "label": "orthopoxvirus gene 027 (MPOX)", + "uri": "GENEPIO:0101217" + }, + "gene_symbol": { + "label": "opg027 gene (MPOX)", + "uri": "GENEPIO:0101392" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551428": { + "type": "gene", + "Dbxref": "NCBIGene:72551428", + "gene_name": { + "label": "orthopoxvirus gene 029 (MPOX)", + "uri": "GENEPIO:0101218" + }, + "gene_symbol": { + "label": "opg029 gene (MPOX)", + "uri": "GENEPIO:0101393" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551429": { + "type": "gene", + "Dbxref": "NCBIGene:72551429", + "gene_name": { + "label": "orthopoxvirus gene 030 (MPOX)", + "uri": "GENEPIO:0101219" + }, + "gene_symbol": { + "label": "opg030 gene (MPOX)", + "uri": "GENEPIO:0101394" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551430": { + "type": "gene", + "Dbxref": "NCBIGene:72551430", + "gene_name": { + "label": "orthopoxvirus gene 031 (MPOX)", + "uri": "GENEPIO:0101220" + }, + "gene_symbol": { + "label": "opg031 gene (MPOX)", + "uri": "GENEPIO:0101395" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551431": { + "type": "gene", + "Dbxref": "NCBIGene:72551431", + "gene_name": { + "label": "orthopoxvirus gene 034 (MPOX)", + "uri": "GENEPIO:0101221" + }, + "gene_symbol": { + "label": "opg034 gene (MPOX)", + "uri": "GENEPIO:0101396" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551432": { + "type": "gene", + "Dbxref": "NCBIGene:72551432", + "gene_name": { + "label": "orthopoxvirus gene 035 (MPOX)", + "uri": "GENEPIO:0101222" + }, + "gene_symbol": { + "label": "opg035 gene (MPOX)", + "uri": "GENEPIO:0101397" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551434": { + "type": "gene", + "Dbxref": "NCBIGene:72551434", + "gene_name": { + "label": "orthopoxvirus gene 037 (MPOX)", + "uri": "GENEPIO:0101224" + }, + "gene_symbol": { + "label": "opg037 gene (MPOX)", + "uri": "GENEPIO:0101399" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551435": { + "type": "gene", + "Dbxref": "NCBIGene:72551435", + "gene_name": { + "label": "orthopoxvirus gene 038 (MPOX)", + "uri": "GENEPIO:0101225" + }, + "gene_symbol": { + "label": "opg038 gene (MPOX)", + "uri": "GENEPIO:0101400" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551436": { + "type": "gene", + "Dbxref": "NCBIGene:72551436", + "gene_name": { + "label": "orthopoxvirus gene 039 (MPOX)", + "uri": "GENEPIO:0101226" + }, + "gene_symbol": { + "label": "opg039 gene (MPOX)", + "uri": "GENEPIO:0101401" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551437": { + "type": "gene", + "Dbxref": "NCBIGene:72551437", + "gene_name": { + "label": "orthopoxvirus gene 040 (MPOX)", + "uri": "GENEPIO:0101227" + }, + "gene_symbol": { + "label": "opg040 gene (MPOX)", + "uri": "GENEPIO:0101402" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551438": { + "type": "gene", + "Dbxref": "NCBIGene:72551438", + "gene_name": { + "label": "orthopoxvirus gene 042 (MPOX)", + "uri": "GENEPIO:0101228" + }, + "gene_symbol": { + "label": "opg042 gene (MPOX)", + "uri": "GENEPIO:0101403" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551439": { + "type": "gene", + "Dbxref": "NCBIGene:72551439", + "gene_name": { + "label": "orthopoxvirus gene 043 (MPOX)", + "uri": "GENEPIO:0101229" + }, + "gene_symbol": { + "label": "opg043 gene (MPOX)", + "uri": "GENEPIO:0101404" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551441": { + "type": "gene", + "Dbxref": "NCBIGene:72551441", + "gene_name": { + "label": "orthopoxvirus gene 045 (MPOX)", + "uri": "GENEPIO:0101231" + }, + "gene_symbol": { + "label": "opg045 gene (MPOX)", + "uri": "GENEPIO:0101406" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551442": { + "type": "gene", + "Dbxref": "NCBIGene:72551442", + "gene_name": { + "label": "orthopoxvirus gene 046 (MPOX)", + "uri": "GENEPIO:0101232" + }, + "gene_symbol": { + "label": "opg046 gene (MPOX)", + "uri": "GENEPIO:0101407" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551443": { + "type": "gene", + "Dbxref": "NCBIGene:72551443", + "gene_name": { + "label": "orthopoxvirus gene 047 (MPOX)", + "uri": "GENEPIO:0101233" + }, + "gene_symbol": { + "label": "opg047 gene (MPOX)", + "uri": "GENEPIO:0101408" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551444": { + "type": "gene", + "Dbxref": "NCBIGene:72551444", + "gene_name": { + "label": "orthopoxvirus gene 048 (MPOX)", + "uri": "GENEPIO:0101234" + }, + "gene_symbol": { + "label": "opg048 gene (MPOX)", + "uri": "GENEPIO:0101409" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551445": { + "type": "gene", + "Dbxref": "NCBIGene:72551445", + "gene_name": { + "label": "orthopoxvirus gene 049 (MPOX)", + "uri": "GENEPIO:0101235" + }, + "gene_symbol": { + "label": "opg049 gene (MPOX)", + "uri": "GENEPIO:0101410" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551446": { + "type": "gene", + "Dbxref": "NCBIGene:72551446", + "gene_name": { + "label": "orthopoxvirus gene 050 (MPOX)", + "uri": "GENEPIO:0101236" + }, + "gene_symbol": { + "label": "opg050 gene (MPOX)", + "uri": "GENEPIO:0101411" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551447": { + "type": "gene", + "Dbxref": "NCBIGene:72551447", + "gene_name": { + "label": "orthopoxvirus gene 051 (MPOX)", + "uri": "GENEPIO:0101237" + }, + "gene_symbol": { + "label": "opg051 gene (MPOX)", + "uri": "GENEPIO:0101412" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551448": { + "type": "gene", + "Dbxref": "NCBIGene:72551448", + "gene_name": { + "label": "orthopoxvirus gene 052 (MPOX)", + "uri": "GENEPIO:0101238" + }, + "gene_symbol": { + "label": "opg052 gene (MPOX)", + "uri": "GENEPIO:0101413" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551449": { + "type": "gene", + "Dbxref": "NCBIGene:72551449", + "gene_name": { + "label": "orthopoxvirus gene 053 (MPOX)", + "uri": "GENEPIO:0101239" + }, + "gene_symbol": { + "label": "opg053 gene (MPOX)", + "uri": "GENEPIO:0101414" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551450": { + "type": "gene", + "Dbxref": "NCBIGene:72551450", + "gene_name": { + "label": "orthopoxvirus gene 054 (MPOX)", + "uri": "GENEPIO:0101240" + }, + "gene_symbol": { + "label": "opg054 gene (MPOX)", + "uri": "GENEPIO:0101415" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551451": { + "type": "gene", + "Dbxref": "NCBIGene:72551451", + "gene_name": { + "label": "orthopoxvirus gene 055 (MPOX)", + "uri": "GENEPIO:0101241" + }, + "gene_symbol": { + "label": "opg055 gene (MPOX)", + "uri": "GENEPIO:0101416" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551452": { + "type": "gene", + "Dbxref": "NCBIGene:72551452", + "gene_name": { + "label": "orthopoxvirus gene 056 (MPOX)", + "uri": "GENEPIO:0101242" + }, + "gene_symbol": { + "label": "opg056 gene (MPOX)", + "uri": "GENEPIO:0101417" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551453": { + "type": "gene", + "Dbxref": "NCBIGene:72551453", + "gene_name": { + "label": "orthopoxvirus gene 057 (MPOX)", + "uri": "GENEPIO:0101243" + }, + "gene_symbol": { + "label": "opg057 gene (MPOX)", + "uri": "GENEPIO:0101418" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551454": { + "type": "gene", + "Dbxref": "NCBIGene:72551454", + "gene_name": { + "label": "orthopoxvirus gene 058 (MPOX)", + "uri": "GENEPIO:0101244" + }, + "gene_symbol": { + "label": "opg058 gene (MPOX)", + "uri": "GENEPIO:0101419" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551455": { + "type": "gene", + "Dbxref": "NCBIGene:72551455", + "gene_name": { + "label": "orthopoxvirus gene 059 (MPOX)", + "uri": "GENEPIO:0101245" + }, + "gene_symbol": { + "label": "opg059 gene (MPOX)", + "uri": "GENEPIO:0101420" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551456": { + "type": "gene", + "Dbxref": "NCBIGene:72551456", + "gene_name": { + "label": "orthopoxvirus gene 060 (MPOX)", + "uri": "GENEPIO:0101246" + }, + "gene_symbol": { + "label": "opg060 gene (MPOX)", + "uri": "GENEPIO:0101421" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551457": { + "type": "gene", + "Dbxref": "NCBIGene:72551457", + "gene_name": { + "label": "orthopoxvirus gene 061 (MPOX)", + "uri": "GENEPIO:0101247" + }, + "gene_symbol": { + "label": "opg061 gene (MPOX)", + "uri": "GENEPIO:0101422" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551458": { + "type": "gene", + "Dbxref": "NCBIGene:72551458", + "gene_name": { + "label": "orthopoxvirus gene 062 (MPOX)", + "uri": "GENEPIO:0101248" + }, + "gene_symbol": { + "label": "opg062 gene (MPOX)", + "uri": "GENEPIO:0101423" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551459": { + "type": "gene", + "Dbxref": "NCBIGene:72551459", + "gene_name": { + "label": "orthopoxvirus gene 063 (MPOX)", + "uri": "GENEPIO:0101249" + }, + "gene_symbol": { + "label": "opg063 gene (MPOX)", + "uri": "GENEPIO:0101424" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551460": { + "type": "gene", + "Dbxref": "NCBIGene:72551460", + "gene_name": { + "label": "orthopoxvirus gene 064 (MPOX)", + "uri": "GENEPIO:0101250" + }, + "gene_symbol": { + "label": "opg064 gene (MPOX)", + "uri": "GENEPIO:0101425" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } + }, + "NCBIGene:72551461": { + "type": "gene", + "Dbxref": "NCBIGene:72551461", + "gene_name": { + "label": "orthopoxvirus gene 065 (MPOX)", + 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"Ser/thr kinase protein (MPOX)", + "uri": "GENEPIO:0101703" + }, + "protein_symbol": { + "label": "Opg187 protein (MPOX)", + "uri": "GENEPIO:0101873" + } + }, + "YP_010377168.1": { + "type": "CDS", + "protein_id": "YP_010377168.1", + "protein_name": { + "label": "Ser/thr kinase protein (MPOX)", + "uri": "GENEPIO:0101703" + }, + "protein_symbol": { + "label": "Opg198 protein (MPOX)", + "uri": "GENEPIO:0101882" + } + }, + "YP_010377160.1": { + "type": "CDS", + "protein_id": "YP_010377160.1", + "protein_name": { + "label": "Schlafen (1) protein (MPOX)", + "uri": "GENEPIO:0101704" + }, + "protein_symbol": { + "label": "Opg188 protein (MPOX)", + "uri": "GENEPIO:0101874" + } + }, + "YP_010377162.1": { + "type": "CDS", + "protein_id": "YP_010377162.1", + "protein_name": { + "label": "EEV type-I membrane glycoprotein (MPOX)", + "uri": "GENEPIO:0101705" + }, + "protein_symbol": { + "label": "Opg190 protein (MPOX)", + "uri": "GENEPIO:0101876" + } + }, + "YP_010377163.1": { + "type": "CDS", + "protein_id": "YP_010377163.1", + "protein_name": { + "label": "Ankyrin-like protein (46) (MPOX)", + "uri": "GENEPIO:0101706" + }, + "protein_symbol": { + "label": "Opg191 protein (MPOX)", + "uri": "GENEPIO:0101877" + } + }, + "YP_010377164.1": { + "type": "CDS", + "protein_id": "YP_010377164.1", + "protein_name": { + "label": "Virulence protein (MPOX)", + "uri": "GENEPIO:0101707" + }, + "protein_symbol": { + "label": "Opg192 protein (MPOX)", + "uri": "GENEPIO:0101878" + } + }, + "YP_010377175.1": { + "type": "CDS", + "protein_id": "YP_010377175.1", + "protein_name": { + "label": "Virulence protein (MPOX)", + "uri": "GENEPIO:0101707" + }, + "protein_symbol": { + "label": "Opg209 protein (MPOX)", + "uri": "GENEPIO:0101888" + } + }, + "YP_010377165.1": { + "type": "CDS", + "protein_id": "YP_010377165.1", + "protein_name": { + "label": "Soluble interferon-gamma receptor-like protein (MPOX)", + "uri": "GENEPIO:0101708" + }, + "protein_symbol": { + "label": "Opg193 protein (MPOX)", + "uri": "GENEPIO:0101879" + } + }, + "YP_010377166.1": { + "type": "CDS", + "protein_id": "YP_010377166.1", + "protein_name": { + "label": "Intracellular viral protein (MPOX)", + "uri": "GENEPIO:0101709" + }, + "protein_symbol": { + "label": "Opg195 protein (MPOX)", + "uri": "GENEPIO:0101880" + } + }, + "YP_010377167.1": { + "type": "CDS", + "protein_id": "YP_010377167.1", + "protein_name": { + "label": "CPXV205 protein (MPOX)", + "uri": "GENEPIO:0101710" + }, + "protein_symbol": { + "label": "Opg197 protein (MPOX)", + "uri": "GENEPIO:0101881" + } + }, + "YP_010377172.1": { + "type": "CDS", + "protein_id": "YP_010377172.1", + "protein_name": { + "label": "IFN-alpha/beta-receptor-like secreted glycoprotein (MPOX)", + "uri": "GENEPIO:0101711" + }, + "protein_symbol": { + "label": "Opg204 protein (MPOX)", + "uri": "GENEPIO:0101885" + } + }, + "YP_010377173.1": { + "type": "CDS", + "protein_id": "YP_010377173.1", + "protein_name": { + "label": "Ankyrin repeat protein (44) (MPOX)", + "uri": "GENEPIO:0101712" + }, + "protein_symbol": { + "label": "Opg205 protein (MPOX)", + "uri": "GENEPIO:0101886" + } + }, + "YP_010377176.1": { + "type": "CDS", + "protein_id": "YP_010377176.1", + "protein_name": { + "label": "B22R family protein (MPOX)", + "uri": "GENEPIO:0101713" + }, + "protein_symbol": { + "label": "Opg210 protein (MPOX)", + "uri": "GENEPIO:0101889" + } + }, + "YP_010377184.1": { + "type": "CDS", + "protein_id": "YP_010377184.1", + "protein_name": { + "label": "Brix domain protein (MPOX)", + "uri": "GENEPIO:0101714" + }, + "protein_symbol": { + "label": "Opg016 protein (MPOX)", + "uri": "GENEPIO:0101891" + } + } +} \ No newline at end of file From a4f40bb09ebd9157fd711755eb450fc791824950 Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 30 Sep 2024 18:20:01 -0700 Subject: [PATCH 043/161] Add strand orientation for MPOX --- .../NC_063383.1_ontology_genes.json | 704 ++++++++++++++++++ bin/robot2json.py | 11 +- 2 files changed, 713 insertions(+), 2 deletions(-) diff --git a/assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ontology_genes.json b/assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ontology_genes.json index 58f2f08b..8e54f762 100644 --- a/assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ontology_genes.json +++ b/assets/virus_ontologyTerms/NC_063383.1/NC_063383.1_ontology_genes.json @@ -10,6 +10,10 @@ "label": "opg001 gene (MPOX)", "uri": "GENEPIO:0101382" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -26,6 +30,10 @@ "label": "opg001 gene (MPOX)", "uri": "GENEPIO:0101382" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "reverse gene orientation", "uri": "GENEPIO:0700005" @@ -42,6 +50,10 @@ "label": "opg002 gene (MPOX)", "uri": "GENEPIO:0101383" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -58,6 +70,10 @@ "label": "opg002 gene (MPOX)", "uri": "GENEPIO:0101383" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "reverse gene orientation", "uri": "GENEPIO:0700005" @@ -74,6 +90,10 @@ "label": "opg003 gene (MPOX)", "uri": "GENEPIO:0101384" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -90,6 +110,10 @@ "label": "opg003 gene (MPOX)", "uri": "GENEPIO:0101384" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "reverse gene orientation", "uri": "GENEPIO:0700005" @@ -106,6 +130,10 @@ "label": "opg015 gene (MPOX)", "uri": "GENEPIO:0101385" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -122,6 +150,10 @@ "label": "opg015 gene (MPOX)", "uri": "GENEPIO:0101385" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "reverse gene orientation", "uri": "GENEPIO:0700005" @@ -138,6 +170,10 @@ "label": "opg019 gene (MPOX)", "uri": "GENEPIO:0101386" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -154,6 +190,10 @@ "label": "opg021 gene (MPOX)", "uri": "GENEPIO:0101387" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -170,6 +210,10 @@ "label": "opg022 gene (MPOX)", "uri": "GENEPIO:0101388" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -186,6 +230,10 @@ "label": "opg023 gene (MPOX)", "uri": "GENEPIO:0101389" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -202,6 +250,10 @@ "label": "opg024 gene (MPOX)", "uri": "GENEPIO:0101390" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -218,6 +270,10 @@ "label": "opg025 gene (MPOX)", "uri": "GENEPIO:0101391" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -234,6 +290,10 @@ "label": "opg027 gene (MPOX)", "uri": "GENEPIO:0101392" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -250,6 +310,10 @@ "label": "opg029 gene (MPOX)", "uri": "GENEPIO:0101393" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -266,6 +330,10 @@ "label": "opg030 gene (MPOX)", "uri": "GENEPIO:0101394" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -282,6 +350,10 @@ "label": "opg031 gene (MPOX)", "uri": "GENEPIO:0101395" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -298,6 +370,10 @@ "label": "opg034 gene (MPOX)", "uri": "GENEPIO:0101396" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -314,6 +390,10 @@ "label": "opg035 gene (MPOX)", "uri": "GENEPIO:0101397" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -330,6 +410,10 @@ "label": "opg037 gene (MPOX)", "uri": "GENEPIO:0101399" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -346,6 +430,10 @@ "label": "opg038 gene (MPOX)", "uri": "GENEPIO:0101400" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -362,6 +450,10 @@ "label": "opg039 gene (MPOX)", "uri": "GENEPIO:0101401" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -378,6 +470,10 @@ "label": "opg040 gene (MPOX)", "uri": "GENEPIO:0101402" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -394,6 +490,10 @@ "label": "opg042 gene (MPOX)", "uri": "GENEPIO:0101403" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -410,6 +510,10 @@ "label": "opg043 gene (MPOX)", "uri": "GENEPIO:0101404" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -426,6 +530,10 @@ "label": "opg045 gene (MPOX)", "uri": "GENEPIO:0101406" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -442,6 +550,10 @@ "label": "opg046 gene (MPOX)", "uri": "GENEPIO:0101407" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -458,6 +570,10 @@ "label": "opg047 gene (MPOX)", "uri": "GENEPIO:0101408" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -474,6 +590,10 @@ "label": "opg048 gene (MPOX)", "uri": "GENEPIO:0101409" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -490,6 +610,10 @@ "label": "opg049 gene (MPOX)", "uri": "GENEPIO:0101410" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -506,6 +630,10 @@ "label": "opg050 gene (MPOX)", "uri": "GENEPIO:0101411" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -522,6 +650,10 @@ "label": "opg051 gene (MPOX)", "uri": "GENEPIO:0101412" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -538,6 +670,10 @@ "label": "opg052 gene (MPOX)", "uri": "GENEPIO:0101413" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -554,6 +690,10 @@ "label": "opg053 gene (MPOX)", "uri": "GENEPIO:0101414" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -570,6 +710,10 @@ "label": "opg054 gene (MPOX)", "uri": "GENEPIO:0101415" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -586,6 +730,10 @@ "label": "opg055 gene (MPOX)", "uri": "GENEPIO:0101416" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -602,6 +750,10 @@ "label": "opg056 gene (MPOX)", "uri": "GENEPIO:0101417" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -618,6 +770,10 @@ "label": "opg057 gene (MPOX)", "uri": "GENEPIO:0101418" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -634,6 +790,10 @@ "label": "opg058 gene (MPOX)", "uri": "GENEPIO:0101419" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -650,6 +810,10 @@ "label": "opg059 gene (MPOX)", "uri": "GENEPIO:0101420" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -666,6 +830,10 @@ "label": "opg060 gene (MPOX)", "uri": "GENEPIO:0101421" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -682,6 +850,10 @@ "label": "opg061 gene (MPOX)", "uri": "GENEPIO:0101422" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -698,6 +870,10 @@ "label": "opg062 gene (MPOX)", "uri": "GENEPIO:0101423" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -714,6 +890,10 @@ "label": "opg063 gene (MPOX)", "uri": "GENEPIO:0101424" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -730,6 +910,10 @@ "label": "opg064 gene (MPOX)", "uri": "GENEPIO:0101425" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -746,6 +930,10 @@ "label": "opg065 gene (MPOX)", "uri": "GENEPIO:0101426" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -762,6 +950,10 @@ "label": "opg066 gene (MPOX)", "uri": "GENEPIO:0101427" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -778,6 +970,10 @@ "label": "opg068 gene (MPOX)", "uri": "GENEPIO:0101428" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -794,6 +990,10 @@ "label": "opg069 gene (MPOX)", "uri": "GENEPIO:0101429" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -810,6 +1010,10 @@ "label": "opg070 gene (MPOX)", "uri": "GENEPIO:0101430" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -826,6 +1030,10 @@ "label": "opg071 gene (MPOX)", "uri": "GENEPIO:0101431" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -842,6 +1050,10 @@ "label": "opg072 gene (MPOX)", "uri": "GENEPIO:0101432" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -858,6 +1070,10 @@ "label": "opg073 gene (MPOX)", "uri": "GENEPIO:0101433" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -874,6 +1090,10 @@ "label": "opg074 gene (MPOX)", "uri": "GENEPIO:0101434" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -890,6 +1110,10 @@ "label": "opg075 gene (MPOX)", "uri": "GENEPIO:0101435" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -906,6 +1130,10 @@ "label": "opg077 gene (MPOX)", "uri": "GENEPIO:0101437" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -922,6 +1150,10 @@ "label": "opg078 gene (MPOX)", "uri": "GENEPIO:0101438" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -938,6 +1170,10 @@ "label": "opg079 gene (MPOX)", "uri": "GENEPIO:0101439" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -954,6 +1190,10 @@ "label": "opg080 gene (MPOX)", "uri": "GENEPIO:0101440" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -970,6 +1210,10 @@ "label": "opg081 gene (MPOX)", "uri": "GENEPIO:0101441" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -986,6 +1230,10 @@ "label": "opg082 gene (MPOX)", "uri": "GENEPIO:0101442" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1002,6 +1250,10 @@ "label": "opg083 gene (MPOX)", "uri": "GENEPIO:0101443" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1018,6 +1270,10 @@ "label": "opg084 gene (MPOX)", "uri": "GENEPIO:0101444" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1034,6 +1290,10 @@ "label": "opg085 gene (MPOX)", "uri": "GENEPIO:0101445" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1050,6 +1310,10 @@ "label": "opg086 gene (MPOX)", "uri": "GENEPIO:0101446" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1066,6 +1330,10 @@ "label": "opg087 gene (MPOX)", "uri": "GENEPIO:0101447" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1082,6 +1350,10 @@ "label": "opg088 gene (MPOX)", "uri": "GENEPIO:0101448" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1098,6 +1370,10 @@ "label": "opg089 gene (MPOX)", "uri": "GENEPIO:0101449" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1114,6 +1390,10 @@ "label": "opg090 gene (MPOX)", "uri": "GENEPIO:0101450" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1130,6 +1410,10 @@ "label": "opg091 gene (MPOX)", "uri": "GENEPIO:0101451" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1146,6 +1430,10 @@ "label": "opg092 gene (MPOX)", "uri": "GENEPIO:0101452" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1162,6 +1450,10 @@ "label": "opg093 gene (MPOX)", "uri": "GENEPIO:0101453" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1178,6 +1470,10 @@ "label": "opg094 gene (MPOX)", "uri": "GENEPIO:0101454" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1194,6 +1490,10 @@ "label": "opg095 gene (MPOX)", "uri": "GENEPIO:0101455" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1210,6 +1510,10 @@ "label": "opg096 gene (MPOX)", "uri": "GENEPIO:0101456" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1226,6 +1530,10 @@ "label": "opg097 gene (MPOX)", "uri": "GENEPIO:0101457" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1242,6 +1550,10 @@ "label": "opg098 gene (MPOX)", "uri": "GENEPIO:0101458" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1258,6 +1570,10 @@ "label": "opg099 gene (MPOX)", "uri": "GENEPIO:0101459" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1274,6 +1590,10 @@ "label": "opg100 gene (MPOX)", "uri": "GENEPIO:0101460" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1290,6 +1610,10 @@ "label": "opg101 gene (MPOX)", "uri": "GENEPIO:0101461" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1306,6 +1630,10 @@ "label": "opg102 gene (MPOX)", "uri": "GENEPIO:0101462" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1322,6 +1650,10 @@ "label": "opg103 gene (MPOX)", "uri": "GENEPIO:0101463" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1338,6 +1670,10 @@ "label": "opg104 gene (MPOX)", "uri": "GENEPIO:0101464" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1354,6 +1690,10 @@ "label": "opg105 gene (MPOX)", "uri": "GENEPIO:0101465" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1370,6 +1710,10 @@ "label": "opg106 gene (MPOX)", "uri": "GENEPIO:0101466" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1386,6 +1730,10 @@ "label": "opg107 gene (MPOX)", "uri": "GENEPIO:0101467" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1402,6 +1750,10 @@ "label": "opg108 gene (MPOX)", "uri": "GENEPIO:0101468" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1418,6 +1770,10 @@ "label": "opg109 gene (MPOX)", "uri": "GENEPIO:0101469" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1434,6 +1790,10 @@ "label": "opg110 gene (MPOX)", "uri": "GENEPIO:0101470" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1450,6 +1810,10 @@ "label": "opg111 gene (MPOX)", "uri": "GENEPIO:0101471" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1466,6 +1830,10 @@ "label": "opg112 gene (MPOX)", "uri": "GENEPIO:0101472" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1482,6 +1850,10 @@ "label": "opg113 gene (MPOX)", "uri": "GENEPIO:0101473" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1498,6 +1870,10 @@ "label": "opg114 gene (MPOX)", "uri": "GENEPIO:0101474" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1514,6 +1890,10 @@ "label": "opg115 gene (MPOX)", "uri": "GENEPIO:0101475" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1530,6 +1910,10 @@ "label": "opg116 gene (MPOX)", "uri": "GENEPIO:0101476" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1546,6 +1930,10 @@ "label": "opg117 gene (MPOX)", "uri": "GENEPIO:0101477" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1562,6 +1950,10 @@ "label": "opg118 gene (MPOX)", "uri": "GENEPIO:0101478" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1578,6 +1970,10 @@ "label": "opg119 gene (MPOX)", "uri": "GENEPIO:0101479" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1594,6 +1990,10 @@ "label": "opg120 gene (MPOX)", "uri": "GENEPIO:0101480" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1610,6 +2010,10 @@ "label": "opg121 gene (MPOX)", "uri": "GENEPIO:0101481" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1626,6 +2030,10 @@ "label": "opg122 gene (MPOX)", "uri": "GENEPIO:0101482" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1642,6 +2050,10 @@ "label": "opg123 gene (MPOX)", "uri": "GENEPIO:0101483" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1658,6 +2070,10 @@ "label": "opg124 gene (MPOX)", "uri": "GENEPIO:0101484" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1674,6 +2090,10 @@ "label": "opg125 gene (MPOX)", "uri": "GENEPIO:0101485" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1690,6 +2110,10 @@ "label": "opg126 gene (MPOX)", "uri": "GENEPIO:0101486" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1706,6 +2130,10 @@ "label": "opg127 gene (MPOX)", "uri": "GENEPIO:0101487" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1722,6 +2150,10 @@ "label": "opg128 gene (MPOX)", "uri": "GENEPIO:0101488" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1738,6 +2170,10 @@ "label": "opg129 gene (MPOX)", "uri": "GENEPIO:0101489" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1754,6 +2190,10 @@ "label": "opg130 gene (MPOX)", "uri": "GENEPIO:0101490" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1770,6 +2210,10 @@ "label": "opg131 gene (MPOX)", "uri": "GENEPIO:0101491" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1786,6 +2230,10 @@ "label": "opg132 gene (MPOX)", "uri": "GENEPIO:0101492" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1802,6 +2250,10 @@ "label": "opg133 gene (MPOX)", "uri": "GENEPIO:0101493" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1818,6 +2270,10 @@ "label": "opg134 gene (MPOX)", "uri": "GENEPIO:0101494" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1834,6 +2290,10 @@ "label": "opg135 gene (MPOX)", "uri": "GENEPIO:0101495" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1850,6 +2310,10 @@ "label": "opg136 gene (MPOX)", "uri": "GENEPIO:0101496" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1866,6 +2330,10 @@ "label": "opg137 gene (MPOX)", "uri": "GENEPIO:0101497" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1882,6 +2350,10 @@ "label": "opg138 gene (MPOX)", "uri": "GENEPIO:0101498" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1898,6 +2370,10 @@ "label": "opg139 gene (MPOX)", "uri": "GENEPIO:0101499" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1914,6 +2390,10 @@ "label": "opg140 gene (MPOX)", "uri": "GENEPIO:0101500" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1930,6 +2410,10 @@ "label": "opg141 gene (MPOX)", "uri": "GENEPIO:0101501" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1946,6 +2430,10 @@ "label": "opg142 gene (MPOX)", "uri": "GENEPIO:0101502" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1962,6 +2450,10 @@ "label": "opg143 gene (MPOX)", "uri": "GENEPIO:0101503" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1978,6 +2470,10 @@ "label": "opg144 gene (MPOX)", "uri": "GENEPIO:0101504" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -1994,6 +2490,10 @@ "label": "opg145 gene (MPOX)", "uri": "GENEPIO:0101505" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2010,6 +2510,10 @@ "label": "opg146 gene (MPOX)", "uri": "GENEPIO:0101506" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2026,6 +2530,10 @@ "label": "opg147 gene (MPOX)", "uri": "GENEPIO:0101507" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2042,6 +2550,10 @@ "label": "opg148 gene (MPOX)", "uri": "GENEPIO:0101508" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2058,6 +2570,10 @@ "label": "opg149 gene (MPOX)", "uri": "GENEPIO:0101509" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2074,6 +2590,10 @@ "label": "opg150 gene (MPOX)", "uri": "GENEPIO:0101510" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2090,6 +2610,10 @@ "label": "opg151 gene (MPOX)", "uri": "GENEPIO:0101511" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2106,6 +2630,10 @@ "label": "opg153 gene (MPOX)", "uri": "GENEPIO:0101512" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2122,6 +2650,10 @@ "label": "opg154 gene (MPOX)", "uri": "GENEPIO:0101513" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2138,6 +2670,10 @@ "label": "opg155 gene (MPOX)", "uri": "GENEPIO:0101514" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2154,6 +2690,10 @@ "label": "opg156 gene (MPOX)", "uri": "GENEPIO:0101515" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2170,6 +2710,10 @@ "label": "opg157 gene (MPOX)", "uri": "GENEPIO:0101516" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2186,6 +2730,10 @@ "label": "opg158 gene (MPOX)", "uri": "GENEPIO:0101517" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2202,6 +2750,10 @@ "label": "opg159 gene (MPOX)", "uri": "GENEPIO:0101518" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2218,6 +2770,10 @@ "label": "opg160 gene (MPOX)", "uri": "GENEPIO:0101519" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2234,6 +2790,10 @@ "label": "opg161 gene (MPOX)", "uri": "GENEPIO:0101520" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2250,6 +2810,10 @@ "label": "opg162 gene (MPOX)", "uri": "GENEPIO:0101521" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2266,6 +2830,10 @@ "label": "opg163 gene (MPOX)", "uri": "GENEPIO:0101522" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2282,6 +2850,10 @@ "label": "opg164 gene (MPOX)", "uri": "GENEPIO:0101523" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2298,6 +2870,10 @@ "label": "opg165 gene (MPOX)", "uri": "GENEPIO:0101524" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2314,6 +2890,10 @@ "label": "opg166 gene (MPOX)", "uri": "GENEPIO:0101525" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2330,6 +2910,10 @@ "label": "opg167 gene (MPOX)", "uri": "GENEPIO:0101526" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2346,6 +2930,10 @@ "label": "opg170 gene (MPOX)", "uri": "GENEPIO:0101527" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2362,6 +2950,10 @@ "label": "opg171 gene (MPOX)", "uri": "GENEPIO:0101528" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2378,6 +2970,10 @@ "label": "opg172 gene (MPOX)", "uri": "GENEPIO:0101529" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2394,6 +2990,10 @@ "label": "opg173 gene (MPOX)", "uri": "GENEPIO:0101530" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2410,6 +3010,10 @@ "label": "opg174 gene (MPOX)", "uri": "GENEPIO:0101531" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2426,6 +3030,10 @@ "label": "opg175 gene (MPOX)", "uri": "GENEPIO:0101532" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2442,6 +3050,10 @@ "label": "opg176 gene (MPOX)", "uri": "GENEPIO:0101533" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2458,6 +3070,10 @@ "label": "opg178 gene (MPOX)", "uri": "GENEPIO:0101534" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2474,6 +3090,10 @@ "label": "opg180 gene (MPOX)", "uri": "GENEPIO:0101535" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2490,6 +3110,10 @@ "label": "opg181 gene (MPOX)", "uri": "GENEPIO:0101536" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2506,6 +3130,10 @@ "label": "opg185 gene (MPOX)", "uri": "GENEPIO:0101537" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2522,6 +3150,10 @@ "label": "opg187 gene (MPOX)", "uri": "GENEPIO:0101538" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2538,6 +3170,10 @@ "label": "opg188 gene (MPOX)", "uri": "GENEPIO:0101539" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2554,6 +3190,10 @@ "label": "opg189 gene (MPOX)", "uri": "GENEPIO:0101540" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2570,6 +3210,10 @@ "label": "opg190 gene (MPOX)", "uri": "GENEPIO:0101541" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2586,6 +3230,10 @@ "label": "opg191 gene (MPOX)", "uri": "GENEPIO:0101542" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2602,6 +3250,10 @@ "label": "opg192 gene (MPOX)", "uri": "GENEPIO:0101543" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2618,6 +3270,10 @@ "label": "opg193 gene (MPOX)", "uri": "GENEPIO:0101544" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2634,6 +3290,10 @@ "label": "opg195 gene (MPOX)", "uri": "GENEPIO:0101545" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2650,6 +3310,10 @@ "label": "opg197 gene (MPOX)", "uri": "GENEPIO:0101546" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2666,6 +3330,10 @@ "label": "opg198 gene (MPOX)", "uri": "GENEPIO:0101547" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2682,6 +3350,10 @@ "label": "opg199 gene (MPOX)", "uri": "GENEPIO:0101548" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2698,6 +3370,10 @@ "label": "opg200 gene (MPOX)", "uri": "GENEPIO:0101549" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2714,6 +3390,10 @@ "label": "opg204 gene (MPOX)", "uri": "GENEPIO:0101550" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2730,6 +3410,10 @@ "label": "opg205 gene (MPOX)", "uri": "GENEPIO:0101551" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2746,6 +3430,10 @@ "label": "opg208 gene (MPOX)", "uri": "GENEPIO:0101552" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2762,6 +3450,10 @@ "label": "opg209 gene (MPOX)", "uri": "GENEPIO:0101553" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2778,6 +3470,10 @@ "label": "opg210 gene (MPOX)", "uri": "GENEPIO:0101554" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2794,6 +3490,10 @@ "label": "opg005 gene (MPOX)", "uri": "GENEPIO:0101555" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" @@ -2810,6 +3510,10 @@ "label": "opg016 gene (MPOX)", "uri": "GENEPIO:0101556" }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, "gene_orientation": { "label": "forward gene orientation", "uri": "GENEPIO:0700004" diff --git a/bin/robot2json.py b/bin/robot2json.py index 74bdf868..a1518ddd 100644 --- a/bin/robot2json.py +++ b/bin/robot2json.py @@ -67,7 +67,12 @@ def parse_args(): # Define a custom function to create a nested structure # ncbigene and the gene name are all the same, this is causing HAVOC def custom_nested_structure_genes(row): - return {row['Dbxref']: {'type': 'gene', 'Dbxref': row['Dbxref'], 'gene_name': {'label': row['gene_name'], 'uri': row['gene_name_id']}, 'gene_symbol': {'label': row['gene_symbol'], 'uri': row['gene_symbol_id']}, 'gene_orientation': {'label': row['gene_orientation'], 'uri': row['gene_orientation_id']}}} + return {row['Dbxref']: {'type': 'gene', 'Dbxref': row['Dbxref'], + 'gene_name': {'label': row['gene_name'], 'uri': row['gene_name_id']}, + 'gene_symbol': {'label': row['gene_symbol'], 'uri': row['gene_symbol_id']}, + 'strand_orientation': {'label': row['strand_orientation'], 'uri': row['strand_orientation_id']}, + 'gene_orientation': {'label': row['gene_orientation'], 'uri': row['gene_orientation_id']} + }} # Apply the custom function to each row of the DataFrame json_data_custom = genes.apply(custom_nested_structure_genes, axis=1).tolist() # saves a list of dicts @@ -102,7 +107,9 @@ def custom_nested_structure_genes(row): # Define a custom function to create a nested structure def custom_nested_structure_proteins(row): - return {row['protein_id']: {'type': 'CDS', 'protein_id': row['protein_id'], 'protein_name': {'label': row['protein_name'], 'uri': row['protein_name_id']}, 'protein_symbol': {'label': row['protein_symbol'], 'uri': row['protein_symbol_id']}}} + return {row['protein_id']: {'type': 'CDS', 'protein_id': row['protein_id'], + 'protein_name': {'label': row['protein_name'], 'uri': row['protein_name_id']}, + 'protein_symbol': {'label': row['protein_symbol'], 'uri': row['protein_symbol_id']}}} # Apply the custom function to each row of the DataFrame json_data_custom = proteins.apply(custom_nested_structure_proteins, axis=1).tolist() # list of dicts From 5166d9e11a52cb3982759c6630baac6d5b0005bf Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 30 Sep 2024 18:37:58 -0700 Subject: [PATCH 044/161] add gene and strand orientation for MPOX --- .../NC_063383.1/NC_063383.1.json | 4984 +++++++++++++++-- bin/addontologyterms2json.py | 4 + 2 files changed, 4632 insertions(+), 356 deletions(-) diff --git a/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json b/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json index 32ce2aeb..4bba8b06 100644 --- a/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json +++ b/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json @@ -27,7 +27,23 @@ "gene": "OPG001", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp001", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-001" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-001", + "gene_name": { + "label": "orthopoxvirus gene 001 (MPOX)", + "uri": "GENEPIO:0101207" + }, + "gene_symbol": { + "label": "opg001 gene (MPOX)", + "uri": "GENEPIO:0101382" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp001": { "type": "CDS", @@ -45,7 +61,15 @@ "protein_id": "YP_010377002.1", "aa_start": 1, "aa_end": 246, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Chemokine binding protein (MPOX)", + "uri": "GENEPIO:0101557" + }, + "protein_symbol": { + "label": "Opg001 protein (MPOX)", + "uri": "GENEPIO:0101720" + } }, "gene-NBT03_gp002": { "type": "gene", @@ -58,7 +82,23 @@ "gene": "OPG002", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp002", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-002" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-002", + "gene_name": { + "label": "orthopoxvirus gene 002 (MPOX)", + "uri": "GENEPIO:0101208" + }, + "gene_symbol": { + "label": "opg002 gene (MPOX)", + "uri": "GENEPIO:0101383" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp002": { "type": "CDS", @@ -76,7 +116,15 @@ "protein_id": "YP_010377003.1", "aa_start": 1, "aa_end": 349, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "Crm-B secreted TNF-alpha-receptor-like protein (MPOX)", + "uri": "GENEPIO:0101558" + }, + "protein_symbol": { + "label": "Opg002 protein (MPOX)", + "uri": "GENEPIO:0101721" + } }, "gene-NBT03_gp003": { "type": "gene", @@ -89,7 +137,23 @@ "gene": "OPG003", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp003", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-003" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-003", + "gene_name": { + "label": "orthopoxvirus gene 003 (MPOX)", + "uri": "GENEPIO:0101209" + }, + "gene_symbol": { + "label": "opg003 gene (MPOX)", + "uri": "GENEPIO:0101384" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp003": { "type": "CDS", @@ -107,7 +171,15 @@ "protein_id": "YP_010377004.1", "aa_start": 1, "aa_end": 588, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "Ankyrin repeat protein (25) (MPOX)", + "uri": "GENEPIO:0101559" + }, + "protein_symbol": { + "label": "Opg003 protein (MPOX)", + "uri": "GENEPIO:0101722" + } }, "gene-NBT03_gp004": { "type": "gene", @@ -120,7 +192,23 @@ "gene": "OPG015", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp004", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-004" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-004", + "gene_name": { + "label": "orthopoxvirus gene 015 (MPOX)", + "uri": "GENEPIO:0101210" + }, + "gene_symbol": { + "label": "opg015 gene (MPOX)", + "uri": "GENEPIO:0101385" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp004": { "type": "CDS", @@ -138,7 +226,15 @@ "protein_id": "YP_010377005.1", "aa_start": 1, "aa_end": 437, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "Ankyrin repeat protein (39) (MPOX)", + "uri": "GENEPIO:0101560" + }, + "protein_symbol": { + "label": "Opg015 protein (MPOX)", + "uri": "GENEPIO:0101723" + } }, "gene-NBT03_gp005": { "type": "gene", @@ -151,7 +247,23 @@ "gene": "OPG019", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp005", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-006" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-006", + "gene_name": { + "label": "orthopoxvirus gene 019 (MPOX)", + "uri": "GENEPIO:0101211" + }, + "gene_symbol": { + "label": "opg019 gene (MPOX)", + "uri": "GENEPIO:0101386" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp006": { "type": "CDS", @@ -169,7 +281,15 @@ "protein_id": "YP_010377006.1", "aa_start": 1, "aa_end": 142, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "EGF-like domain protein (MPOX)", + "uri": "GENEPIO:0101561" + }, + "protein_symbol": { + "label": "Opg019 protein (MPOX)", + "uri": "GENEPIO:0101724" + } }, "gene-NBT03_gp006": { "type": "gene", @@ -182,7 +302,23 @@ "gene": "OPG021", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp006", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-008" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-008", + "gene_name": { + "label": "orthopoxvirus gene 021 (MPOX)", + "uri": "GENEPIO:0101212" + }, + "gene_symbol": { + "label": "opg021 gene (MPOX)", + "uri": "GENEPIO:0101387" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp008": { "type": "CDS", @@ -200,7 +336,15 @@ "protein_id": "YP_010377007.1", "aa_start": 1, "aa_end": 242, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "Zinc finger-like protein (2) (MPOX)", + "uri": "GENEPIO:0101562" + }, + "protein_symbol": { + "label": "Opg021 protein (MPOX)", + "uri": "GENEPIO:0101725" + } }, "gene-NBT03_gp007": { "type": "gene", @@ -213,7 +357,23 @@ "gene": "OPG022", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp007", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-009" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-009", + "gene_name": { + "label": "orthopoxvirus gene 022 (MPOX)", + "uri": "GENEPIO:0101213" + }, + "gene_symbol": { + "label": "opg022 gene (MPOX)", + "uri": "GENEPIO:0101388" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp009": { "type": "CDS", @@ -231,7 +391,15 @@ "protein_id": "YP_010377008.1", "aa_start": 1, "aa_end": 126, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "Interleukin-18-binding protein (MPOX)", + "uri": "GENEPIO:0101563" + }, + "protein_symbol": { + "label": "Opg022 protein (MPOX)", + "uri": "GENEPIO:0101726" + } }, "gene-NBT03_gp008": { "type": "gene", @@ -244,7 +412,23 @@ "gene": "OPG023", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp008", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-010" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-010", + "gene_name": { + "label": "orthopoxvirus gene 023 (MPOX)", + "uri": "GENEPIO:0101214" + }, + "gene_symbol": { + "label": "opg023 gene (MPOX)", + "uri": "GENEPIO:0101389" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp010": { "type": "CDS", @@ -262,7 +446,15 @@ "protein_id": "YP_010377009.1", "aa_start": 1, "aa_end": 660, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "Ankyrin repeat protein (2) (MPOX)", + "uri": "GENEPIO:0101564" + }, + "protein_symbol": { + "label": "Opg023 protein (MPOX)", + "uri": "GENEPIO:0101727" + } }, "gene-NBT03_gp009": { "type": "gene", @@ -275,7 +467,23 @@ "gene": "OPG024", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp009", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-011" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-011", + "gene_name": { + "label": "orthopoxvirus gene 024 (MPOX)", + "uri": "GENEPIO:0101215" + }, + "gene_symbol": { + "label": "opg024 gene (MPOX)", + "uri": "GENEPIO:0101390" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp011": { "type": "CDS", @@ -293,7 +501,15 @@ "protein_id": "YP_010377010.1", "aa_start": 1, "aa_end": 64, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "retroviral pseudoprotease-like protein (MPOX)", + "uri": "GENEPIO:0101565" + }, + "protein_symbol": { + "label": "Opg024 protein (MPOX)", + "uri": "GENEPIO:0101728" + } }, "gene-NBT03_gp010": { "type": "gene", @@ -306,7 +522,23 @@ "gene": "OPG025", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp010", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-012" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-012", + "gene_name": { + "label": "orthopoxvirus gene 025 (MPOX)", + "uri": "GENEPIO:0101216" + }, + "gene_symbol": { + "label": "opg025 gene (MPOX)", + "uri": "GENEPIO:0101391" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp012": { "type": "CDS", @@ -324,7 +556,15 @@ "protein_id": "YP_010377011.1", "aa_start": 1, "aa_end": 630, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "Ankyrin repeat protein (14) (MPOX)", + "uri": "GENEPIO:0101566" + }, + "protein_symbol": { + "label": "Opg025 protein (MPOX)", + "uri": "GENEPIO:0101729" + } }, "gene-NBT03_gp011": { "type": "gene", @@ -337,7 +577,23 @@ "gene": "OPG027", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp011", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-013" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-013", + "gene_name": { + "label": "orthopoxvirus gene 027 (MPOX)", + "uri": "GENEPIO:0101217" + }, + "gene_symbol": { + "label": "opg027 gene (MPOX)", + "uri": "GENEPIO:0101392" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp013": { "type": "CDS", @@ -355,7 +611,15 @@ "protein_id": "YP_010377012.1", "aa_start": 1, "aa_end": 150, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Host range protein (MPOX)", + "uri": "GENEPIO:0101567" + }, + "protein_symbol": { + "label": "Opg027 protein (MPOX)", + "uri": "GENEPIO:0101730" + } }, "gene-NBT03_gp012": { "type": "gene", @@ -368,7 +632,23 @@ "gene": "OPG029", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp012", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-014" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-014", + "gene_name": { + "label": "orthopoxvirus gene 029 (MPOX)", + "uri": "GENEPIO:0101218" + }, + "gene_symbol": { + "label": "opg029 gene (MPOX)", + "uri": "GENEPIO:0101393" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp014": { "type": "CDS", @@ -386,7 +666,15 @@ "protein_id": "YP_010377013.1", "aa_start": 1, "aa_end": 155, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "Bcl-2-like protein (MPOX)", + "uri": "GENEPIO:0101568" + }, + "protein_symbol": { + "label": "Opg029 protein (MPOX)", + "uri": "GENEPIO:0101731" + } }, "gene-NBT03_gp013": { "type": "gene", @@ -399,7 +687,23 @@ "gene": "OPG030", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp013", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-015" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-015", + "gene_name": { + "label": "orthopoxvirus gene 030 (MPOX)", + "uri": "GENEPIO:0101219" + }, + "gene_symbol": { + "label": "opg030 gene (MPOX)", + "uri": "GENEPIO:0101394" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp015": { "type": "CDS", @@ -417,7 +721,15 @@ "protein_id": "YP_010377014.1", "aa_start": 1, "aa_end": 206, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "Kelch-like protein (1) (MPOX)", + "uri": "GENEPIO:0101569" + }, + "protein_symbol": { + "label": "Opg030 protein (MPOX)", + "uri": "GENEPIO:0101732" + } }, "gene-NBT03_gp014": { "type": "gene", @@ -430,7 +742,23 @@ "gene": "OPG031", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp014", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-016" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-016", + "gene_name": { + "label": "orthopoxvirus gene 031 (MPOX)", + "uri": "GENEPIO:0101220" + }, + "gene_symbol": { + "label": "opg031 gene (MPOX)", + "uri": "GENEPIO:0101395" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp016": { "type": "CDS", @@ -448,7 +776,15 @@ "protein_id": "YP_010377015.1", "aa_start": 1, "aa_end": 316, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "C4L/C10L-like family protein (MPOX)", + "uri": "GENEPIO:0101570" + }, + "protein_symbol": { + "label": "Opg031 protein (MPOX)", + "uri": "GENEPIO:0101733" + } }, "gene-NBT03_gp015": { "type": "gene", @@ -461,7 +797,23 @@ "gene": "OPG034", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp015", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-018" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-018", + "gene_name": { + "label": "orthopoxvirus gene 034 (MPOX)", + "uri": "GENEPIO:0101221" + }, + "gene_symbol": { + "label": "opg034 gene (MPOX)", + "uri": "GENEPIO:0101396" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp022": { "type": "CDS", @@ -479,7 +831,15 @@ "protein_id": "YP_010377017.1", "aa_start": 1, "aa_end": 214, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Bcl-2-like protein (MPOX)", + "uri": "GENEPIO:0101568" + }, + "protein_symbol": { + "label": "Opg034 protein (MPOX)", + "uri": "GENEPIO:0101734" + } }, "gene-NBT03_gp016": { "type": "gene", @@ -492,7 +852,23 @@ "gene": "OPG035", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp016", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-019" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-019", + "gene_name": { + "label": "orthopoxvirus gene 035 (MPOX)", + "uri": "GENEPIO:0101222" + }, + "gene_symbol": { + "label": "opg035 gene (MPOX)", + "uri": "GENEPIO:0101397" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp023": { "type": "CDS", @@ -510,7 +886,15 @@ "protein_id": "YP_010377018.1", "aa_start": 1, "aa_end": 117, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "Bcl-2-like protein (MPOX)", + "uri": "GENEPIO:0101568" + }, + "protein_symbol": { + "label": "Opg035 protein (MPOX)", + "uri": "GENEPIO:0101735" + } }, "gene-NBT03_gp017": { "type": "gene", @@ -523,7 +907,23 @@ "gene": "OPG036", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp017", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-020" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-020", + "gene_name": { + "label": "orthopoxvirus gene 035 (MPOX)", + "uri": "GENEPIO:0101222" + }, + "gene_symbol": { + "label": "opg035 gene (MPOX)", + "uri": "GENEPIO:0101397" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp024": { "type": "CDS", @@ -541,7 +941,15 @@ "protein_id": "YP_010377019.1", "aa_start": 1, "aa_end": 177, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "Bcl-2-like protein (MPOX)", + "uri": "GENEPIO:0101568" + }, + "protein_symbol": { + "label": "Opg035 protein (MPOX)", + "uri": "GENEPIO:0101735" + } }, "gene-NBT03_gp018": { "type": "gene", @@ -554,7 +962,23 @@ "gene": "OPG037", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp018", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-021" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-021", + "gene_name": { + "label": "orthopoxvirus gene 037 (MPOX)", + "uri": "GENEPIO:0101224" + }, + "gene_symbol": { + "label": "opg037 gene (MPOX)", + "uri": "GENEPIO:0101399" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "VP37": { "type": "CDS", @@ -573,7 +997,15 @@ "aa_start": 1, "aa_end": 442, "color": "rgb(196, 185, 69)", - "protein_alias": "VP37" + "protein_alias": "VP37", + "protein_name": { + "label": "Ankyrin-like protein (1) (MPOX)", + "uri": "GENEPIO:0101571" + }, + "protein_symbol": { + "label": "Opg037 protein (MPOX)", + "uri": "GENEPIO:0101736" + } }, "gene-NBT03_gp019": { "type": "gene", @@ -586,7 +1018,23 @@ "gene": "OPG038", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp019", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-022" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-022", + "gene_name": { + "label": "orthopoxvirus gene 038 (MPOX)", + "uri": "GENEPIO:0101225" + }, + "gene_symbol": { + "label": "opg038 gene (MPOX)", + "uri": "GENEPIO:0101400" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp026": { "type": "CDS", @@ -604,7 +1052,15 @@ "protein_id": "YP_010377021.1", "aa_start": 1, "aa_end": 220, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "NFkB inhibitor protein (MPOX)", + "uri": "GENEPIO:0101572" + }, + "protein_symbol": { + "label": "Opg038 protein (MPOX)", + "uri": "GENEPIO:0101737" + } }, "gene-NBT03_gp020": { "type": "gene", @@ -617,7 +1073,23 @@ "gene": "OPG039", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp020", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-023" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-023", + "gene_name": { + "label": "orthopoxvirus gene 039 (MPOX)", + "uri": "GENEPIO:0101226" + }, + "gene_symbol": { + "label": "opg039 gene (MPOX)", + "uri": "GENEPIO:0101401" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp027": { "type": "CDS", @@ -635,7 +1107,15 @@ "protein_id": "YP_010377022.1", "aa_start": 1, "aa_end": 284, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "Ankyrin-like protein (3) (MPOX)", + "uri": "GENEPIO:0101573" + }, + "protein_symbol": { + "label": "Opg039 protein (MPOX)", + "uri": "GENEPIO:0101738" + } }, "gene-NBT03_gp021": { "type": "gene", @@ -648,7 +1128,23 @@ "gene": "OPG040", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp021", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-024" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-024", + "gene_name": { + "label": "orthopoxvirus gene 040 (MPOX)", + "uri": "GENEPIO:0101227" + }, + "gene_symbol": { + "label": "opg040 gene (MPOX)", + "uri": "GENEPIO:0101402" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp028": { "type": "CDS", @@ -666,7 +1162,15 @@ "protein_id": "YP_010377023.1", "aa_start": 1, "aa_end": 375, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Serpin protein (MPOX)", + "uri": "GENEPIO:0101574" + }, + "protein_symbol": { + "label": "Opg040 protein (MPOX)", + "uri": "GENEPIO:0101739" + } }, "gene-NBT03_gp022": { "type": "gene", @@ -679,7 +1183,23 @@ "gene": "OPG042", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp022", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-026" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-026", + "gene_name": { + "label": "orthopoxvirus gene 042 (MPOX)", + "uri": "GENEPIO:0101228" + }, + "gene_symbol": { + "label": "opg042 gene (MPOX)", + "uri": "GENEPIO:0101403" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp030": { "type": "CDS", @@ -697,7 +1217,15 @@ "protein_id": "YP_010377025.1", "aa_start": 1, "aa_end": 424, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "Phospholipase-D-like protein (MPOX)", + "uri": "GENEPIO:0101575" + }, + "protein_symbol": { + "label": "Opg042 protein (MPOX)", + "uri": "GENEPIO:0101740" + } }, "gene-NBT03_gp023": { "type": "gene", @@ -710,7 +1238,23 @@ "gene": "OPG043", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp023", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-027" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-027", + "gene_name": { + "label": "orthopoxvirus gene 043 (MPOX)", + "uri": "GENEPIO:0101229" + }, + "gene_symbol": { + "label": "opg043 gene (MPOX)", + "uri": "GENEPIO:0101404" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp031": { "type": "CDS", @@ -728,7 +1272,15 @@ "protein_id": "YP_010377026.1", "aa_start": 1, "aa_end": 276, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "Putative monoglyceride lipase protein (MPOX)", + "uri": "GENEPIO:0101576" + }, + "protein_symbol": { + "label": "Opg043 protein (MPOX)", + "uri": "GENEPIO:0101741" + } }, "gene-NBT03_gp024": { "type": "gene", @@ -741,7 +1293,23 @@ "gene": "OPG044", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp024", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-028" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-028", + "gene_name": { + "label": "orthopoxvirus gene 043 (MPOX)", + "uri": "GENEPIO:0101229" + }, + "gene_symbol": { + "label": "opg043 gene (MPOX)", + "uri": "GENEPIO:0101404" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp032": { "type": "CDS", @@ -759,7 +1327,15 @@ "protein_id": "YP_010377027.1", "aa_start": 1, "aa_end": 149, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "Putative monoglyceride lipase protein (MPOX)", + "uri": "GENEPIO:0101576" + }, + "protein_symbol": { + "label": "Opg043 protein (MPOX)", + "uri": "GENEPIO:0101741" + } }, "gene-NBT03_gp025": { "type": "gene", @@ -772,7 +1348,23 @@ "gene": "OPG045", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp025", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-029" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-029", + "gene_name": { + "label": "orthopoxvirus gene 045 (MPOX)", + "uri": "GENEPIO:0101231" + }, + "gene_symbol": { + "label": "opg045 gene (MPOX)", + "uri": "GENEPIO:0101406" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp033": { "type": "CDS", @@ -790,7 +1382,15 @@ "protein_id": "YP_010377028.1", "aa_start": 1, "aa_end": 219, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Caspase-9 inhibitor protein (MPOX)", + "uri": "GENEPIO:0101577" + }, + "protein_symbol": { + "label": "Opg045 protein (MPOX)", + "uri": "GENEPIO:0101742" + } }, "gene-NBT03_gp026": { "type": "gene", @@ -803,7 +1403,23 @@ "gene": "OPG046", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp026", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-030" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-030", + "gene_name": { + "label": "orthopoxvirus gene 046 (MPOX)", + "uri": "GENEPIO:0101232" + }, + "gene_symbol": { + "label": "opg046 gene (MPOX)", + "uri": "GENEPIO:0101407" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp034": { "type": "CDS", @@ -821,7 +1437,15 @@ "protein_id": "YP_010377029.1", "aa_start": 1, "aa_end": 151, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "dUTPase protein (MPOX)", + "uri": "GENEPIO:0101578" + }, + "protein_symbol": { + "label": "Opg046 protein (MPOX)", + "uri": "GENEPIO:0101743" + } }, "gene-NBT03_gp027": { "type": "gene", @@ -834,7 +1458,23 @@ "gene": "OPG047", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp027", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-031" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-031", + "gene_name": { + "label": "orthopoxvirus gene 047 (MPOX)", + "uri": "GENEPIO:0101233" + }, + "gene_symbol": { + "label": "opg047 gene (MPOX)", + "uri": "GENEPIO:0101408" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp035": { "type": "CDS", @@ -852,7 +1492,15 @@ "protein_id": "YP_010377030.1", "aa_start": 1, "aa_end": 482, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "Kelch-like protein (2) (MPOX)", + "uri": "GENEPIO:0101579" + }, + "protein_symbol": { + "label": "Opg047 protein (MPOX)", + "uri": "GENEPIO:0101744" + } }, "gene-NBT03_gp028": { "type": "gene", @@ -865,7 +1513,23 @@ "gene": "OPG048", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp028", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-032" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-032", + "gene_name": { + "label": "orthopoxvirus gene 048 (MPOX)", + "uri": "GENEPIO:0101234" + }, + "gene_symbol": { + "label": "opg048 gene (MPOX)", + "uri": "GENEPIO:0101409" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp036": { "type": "CDS", @@ -883,7 +1547,15 @@ "protein_id": "YP_010377031.1", "aa_start": 1, "aa_end": 319, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "Ribonucleotide reductase small subunit protein (MPOX)", + "uri": "GENEPIO:0101580" + }, + "protein_symbol": { + "label": "Opg048 protein (MPOX)", + "uri": "GENEPIO:0101745" + } }, "gene-NBT03_gp029": { "type": "gene", @@ -896,7 +1568,23 @@ "gene": "OPG049", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp029", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-033" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-033", + "gene_name": { + "label": "orthopoxvirus gene 049 (MPOX)", + "uri": "GENEPIO:0101235" + }, + "gene_symbol": { + "label": "opg049 gene (MPOX)", + "uri": "GENEPIO:0101410" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp037": { "type": "CDS", @@ -914,7 +1602,15 @@ "protein_id": "YP_010377032.1", "aa_start": 1, "aa_end": 318, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "Telomere-binding protein I6 (1) (MPOX)", + "uri": "GENEPIO:0101581" + }, + "protein_symbol": { + "label": "Opg049 protein (MPOX)", + "uri": "GENEPIO:0101746" + } }, "gene-NBT03_gp030": { "type": "gene", @@ -927,7 +1623,23 @@ "gene": "OPG050", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp030", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-034" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-034", + "gene_name": { + "label": "orthopoxvirus gene 050 (MPOX)", + "uri": "GENEPIO:0101236" + }, + "gene_symbol": { + "label": "opg050 gene (MPOX)", + "uri": "GENEPIO:0101411" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp038": { "type": "CDS", @@ -945,7 +1657,15 @@ "protein_id": "YP_010377033.1", "aa_start": 1, "aa_end": 75, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "CPXV053 protein (MPOX)", + "uri": "GENEPIO:0101582" + }, + "protein_symbol": { + "label": "Opg050 protein (MPOX)", + "uri": "GENEPIO:0101747" + } }, "gene-NBT03_gp031": { "type": "gene", @@ -958,7 +1678,23 @@ "gene": "OPG051", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp031", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-035" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-035", + "gene_name": { + "label": "orthopoxvirus gene 051 (MPOX)", + "uri": "GENEPIO:0101237" + }, + "gene_symbol": { + "label": "opg051 gene (MPOX)", + "uri": "GENEPIO:0101412" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp039": { "type": "CDS", @@ -976,7 +1712,15 @@ "protein_id": "YP_010377034.1", "aa_start": 1, "aa_end": 74, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "CPXV054 protein (MPOX)", + "uri": "GENEPIO:0101583" + }, + "protein_symbol": { + "label": "Opg051 protein (MPOX)", + "uri": "GENEPIO:0101748" + } }, "gene-NBT03_gp032": { "type": "gene", @@ -989,7 +1733,23 @@ "gene": "OPG052", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp032", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-036" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-036", + "gene_name": { + "label": "orthopoxvirus gene 052 (MPOX)", + "uri": "GENEPIO:0101238" + }, + "gene_symbol": { + "label": "opg052 gene (MPOX)", + "uri": "GENEPIO:0101413" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp040": { "type": "CDS", @@ -1007,7 +1767,15 @@ "protein_id": "YP_010377035.1", "aa_start": 1, "aa_end": 64, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "Cytoplasmic protein (MPOX)", + "uri": "GENEPIO:0101584" + }, + "protein_symbol": { + "label": "Opg052 protein (MPOX)", + "uri": "GENEPIO:0101749" + } }, "gene-NBT03_gp033": { "type": "gene", @@ -1020,7 +1788,23 @@ "gene": "OPG053", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp033", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-037" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-037", + "gene_name": { + "label": "orthopoxvirus gene 053 (MPOX)", + "uri": "GENEPIO:0101239" + }, + "gene_symbol": { + "label": "opg053 gene (MPOX)", + "uri": "GENEPIO:0101414" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp041": { "type": "CDS", @@ -1038,7 +1822,15 @@ "protein_id": "YP_010377036.1", "aa_start": 1, "aa_end": 212, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "IMV membrane protein L1R (MPOX)", + "uri": "GENEPIO:0101585" + }, + "protein_symbol": { + "label": "Opg053 protein (MPOX)", + "uri": "GENEPIO:0101750" + } }, "gene-NBT03_gp034": { "type": "gene", @@ -1051,7 +1843,23 @@ "gene": "OPG054", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp034", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-038" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-038", + "gene_name": { + "label": "orthopoxvirus gene 054 (MPOX)", + "uri": "GENEPIO:0101240" + }, + "gene_symbol": { + "label": "opg054 gene (MPOX)", + "uri": "GENEPIO:0101415" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp042": { "type": "CDS", @@ -1069,7 +1877,15 @@ "protein_id": "YP_010377037.1", "aa_start": 1, "aa_end": 439, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "Serine/threonine-protein kinase (MPOX)", + "uri": "GENEPIO:0101586" + }, + "protein_symbol": { + "label": "Opg054 protein (MPOX)", + "uri": "GENEPIO:0101751" + } }, "gene-NBT03_gp035": { "type": "gene", @@ -1082,7 +1898,23 @@ "gene": "OPG055", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp035", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-039" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-039", + "gene_name": { + "label": "orthopoxvirus gene 055 (MPOX)", + "uri": "GENEPIO:0101241" + }, + "gene_symbol": { + "label": "opg055 gene (MPOX)", + "uri": "GENEPIO:0101416" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp043": { "type": "CDS", @@ -1100,7 +1932,15 @@ "protein_id": "YP_010377038.1", "aa_start": 1, "aa_end": 354, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Protein F11 protein (MPOX)", + "uri": "GENEPIO:0101587" + }, + "protein_symbol": { + "label": "Opg055 protein (MPOX)", + "uri": "GENEPIO:0101752" + } }, "gene-NBT03_gp036": { "type": "gene", @@ -1113,7 +1953,23 @@ "gene": "OPG056", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp036", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-040" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-040", + "gene_name": { + "label": "orthopoxvirus gene 056 (MPOX)", + "uri": "GENEPIO:0101242" + }, + "gene_symbol": { + "label": "opg056 gene (MPOX)", + "uri": "GENEPIO:0101417" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp044": { "type": "CDS", @@ -1131,7 +1987,15 @@ "protein_id": "YP_010377039.1", "aa_start": 1, "aa_end": 635, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "EEV maturation protein (MPOX)", + "uri": "GENEPIO:0101588" + }, + "protein_symbol": { + "label": "Opg056 protein (MPOX)", + "uri": "GENEPIO:0101753" + } }, "gene-NBT03_gp037": { "type": "gene", @@ -1144,7 +2008,23 @@ "gene": "OPG057", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp037", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-041" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-041", + "gene_name": { + "label": "orthopoxvirus gene 057 (MPOX)", + "uri": "GENEPIO:0101243" + }, + "gene_symbol": { + "label": "opg057 gene (MPOX)", + "uri": "GENEPIO:0101418" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp045": { "type": "CDS", @@ -1162,7 +2042,15 @@ "protein_id": "YP_010377040.1", "aa_start": 1, "aa_end": 372, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "Palmytilated EEV membrane protein (MPOX)", + "uri": "GENEPIO:0101589" + }, + "protein_symbol": { + "label": "Opg057 protein (MPOX)", + "uri": "GENEPIO:0101754" + } }, "gene-NBT03_gp038": { "type": "gene", @@ -1175,7 +2063,23 @@ "gene": "OPG058", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp038", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-042" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-042", + "gene_name": { + "label": "orthopoxvirus gene 058 (MPOX)", + "uri": "GENEPIO:0101244" + }, + "gene_symbol": { + "label": "opg058 gene (MPOX)", + "uri": "GENEPIO:0101419" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp046": { "type": "CDS", @@ -1193,7 +2097,15 @@ "protein_id": "YP_010377041.1", "aa_start": 1, "aa_end": 73, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "Protein F14 (1) protein (MPOX)", + "uri": "GENEPIO:0101590" + }, + "protein_symbol": { + "label": "Opg058 protein (MPOX)", + "uri": "GENEPIO:0101755" + } }, "gene-NBT03_gp039": { "type": "gene", @@ -1206,7 +2118,23 @@ "gene": "OPG059", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp039", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-043" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-043", + "gene_name": { + "label": "orthopoxvirus gene 059 (MPOX)", + "uri": "GENEPIO:0101245" + }, + "gene_symbol": { + "label": "opg059 gene (MPOX)", + "uri": "GENEPIO:0101420" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "C20.5L": { "type": "CDS", @@ -1223,7 +2151,15 @@ "protein_id": "YP_010377042.1", "aa_start": 1, "aa_end": 49, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "Cytochrome C oxidase protein (MPOX)", + "uri": "GENEPIO:0101591" + }, + "protein_symbol": { + "label": "Opg059 protein (MPOX)", + "uri": "GENEPIO:0101756" + } }, "gene-NBT03_gp040": { "type": "gene", @@ -1236,7 +2172,23 @@ "gene": "OPG060", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp040", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-044" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-044", + "gene_name": { + "label": "orthopoxvirus gene 060 (MPOX)", + "uri": "GENEPIO:0101246" + }, + "gene_symbol": { + "label": "opg060 gene (MPOX)", + "uri": "GENEPIO:0101421" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp047": { "type": "CDS", @@ -1254,7 +2206,15 @@ "protein_id": "YP_010377043.1", "aa_start": 1, "aa_end": 158, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "Protein F15 protein (MPOX)", + "uri": "GENEPIO:0101592" + }, + "protein_symbol": { + "label": "Opg060 protein (MPOX)", + "uri": "GENEPIO:0101757" + } }, "gene-NBT03_gp041": { "type": "gene", @@ -1267,7 +2227,23 @@ "gene": "OPG061", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp041", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-045" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-045", + "gene_name": { + "label": "orthopoxvirus gene 061 (MPOX)", + "uri": "GENEPIO:0101247" + }, + "gene_symbol": { + "label": "opg061 gene (MPOX)", + "uri": "GENEPIO:0101422" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp048": { "type": "CDS", @@ -1285,7 +2261,15 @@ "protein_id": "YP_010377044.1", "aa_start": 1, "aa_end": 231, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Protein F16 (1) protein (MPOX)", + "uri": "GENEPIO:0101593" + }, + "protein_symbol": { + "label": "Opg061 protein (MPOX)", + "uri": "GENEPIO:0101758" + } }, "gene-NBT03_gp042": { "type": "gene", @@ -1298,7 +2282,23 @@ "gene": "OPG062", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp042", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-046" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-046", + "gene_name": { + "label": "orthopoxvirus gene 062 (MPOX)", + "uri": "GENEPIO:0101248" + }, + "gene_symbol": { + "label": "opg062 gene (MPOX)", + "uri": "GENEPIO:0101423" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp049": { "type": "CDS", @@ -1316,7 +2316,15 @@ "protein_id": "YP_010377045.1", "aa_start": 1, "aa_end": 101, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "DNA-binding phosphoprotein (1) (MPOX)", + "uri": "GENEPIO:0101594" + }, + "protein_symbol": { + "label": "Opg062 protein (MPOX)", + "uri": "GENEPIO:0101759" + } }, "gene-NBT03_gp043": { "type": "gene", @@ -1329,7 +2337,23 @@ "gene": "OPG063", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp043", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-047" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-047", + "gene_name": { + "label": "orthopoxvirus gene 063 (MPOX)", + "uri": "GENEPIO:0101249" + }, + "gene_symbol": { + "label": "opg063 gene (MPOX)", + "uri": "GENEPIO:0101424" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp050": { "type": "CDS", @@ -1347,7 +2371,15 @@ "protein_id": "YP_010377046.1", "aa_start": 1, "aa_end": 479, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "Poly(A) polymerase catalytic subunit (3) protein (MPOX)", + "uri": "GENEPIO:0101595" + }, + "protein_symbol": { + "label": "Opg063 protein (MPOX)", + "uri": "GENEPIO:0101760" + } }, "gene-NBT03_gp044": { "type": "gene", @@ -1360,7 +2392,23 @@ "gene": "OPG064", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp044", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-048" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-048", + "gene_name": { + "label": "orthopoxvirus gene 064 (MPOX)", + "uri": "GENEPIO:0101250" + }, + "gene_symbol": { + "label": "opg064 gene (MPOX)", + "uri": "GENEPIO:0101425" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp051": { "type": "CDS", @@ -1378,7 +2426,15 @@ "protein_id": "YP_010377047.1", "aa_start": 1, "aa_end": 737, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "Iev morphogenesis protein (MPOX)", + "uri": "GENEPIO:0101596" + }, + "protein_symbol": { + "label": "Opg064 protein (MPOX)", + "uri": "GENEPIO:0101761" + } }, "gene-NBT03_gp045": { "type": "gene", @@ -1391,7 +2447,23 @@ "gene": "OPG065", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp045", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-049" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-049", + "gene_name": { + "label": "orthopoxvirus gene 065 (MPOX)", + "uri": "GENEPIO:0101251" + }, + "gene_symbol": { + "label": "opg065 gene (MPOX)", + "uri": "GENEPIO:0101426" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp052": { "type": "CDS", @@ -1409,7 +2481,15 @@ "protein_id": "YP_010377048.1", "aa_start": 1, "aa_end": 153, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Double-stranded RNA binding protein (MPOX)", + "uri": "GENEPIO:0101597" + }, + "protein_symbol": { + "label": "Opg065 protein (MPOX)", + "uri": "GENEPIO:0101762" + } }, "gene-NBT03_gp046": { "type": "gene", @@ -1422,7 +2502,23 @@ "gene": "OPG066", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp046", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-050" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-050", + "gene_name": { + "label": "orthopoxvirus gene 066 (MPOX)", + "uri": "GENEPIO:0101252" + }, + "gene_symbol": { + "label": "opg066 gene (MPOX)", + "uri": "GENEPIO:0101427" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp053": { "type": "CDS", @@ -1440,7 +2536,15 @@ "protein_id": "YP_010377049.1", "aa_start": 1, "aa_end": 259, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "DNA-directed RNA polymerase 30 kDa polypeptide protein (MPOX)", + "uri": "GENEPIO:0101598" + }, + "protein_symbol": { + "label": "Opg066 protein (MPOX)", + "uri": "GENEPIO:0101763" + } }, "gene-NBT03_gp047": { "type": "gene", @@ -1453,7 +2557,23 @@ "gene": "OPG068", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp047", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-052" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-052", + "gene_name": { + "label": "orthopoxvirus gene 068 (MPOX)", + "uri": "GENEPIO:0101253" + }, + "gene_symbol": { + "label": "opg068 gene (MPOX)", + "uri": "GENEPIO:0101428" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp054": { "type": "CDS", @@ -1471,7 +2591,15 @@ "protein_id": "YP_010377051.1", "aa_start": 1, "aa_end": 567, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "IMV membrane protein E6 (MPOX)", + "uri": "GENEPIO:0101599" + }, + "protein_symbol": { + "label": "Opg068 protein (MPOX)", + "uri": "GENEPIO:0101764" + } }, "gene-NBT03_gp048": { "type": "gene", @@ -1484,7 +2612,23 @@ "gene": "OPG069", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp048", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-053" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-053", + "gene_name": { + "label": "orthopoxvirus gene 069 (MPOX)", + "uri": "GENEPIO:0101254" + }, + "gene_symbol": { + "label": "opg069 gene (MPOX)", + "uri": "GENEPIO:0101429" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp055": { "type": "CDS", @@ -1502,7 +2646,15 @@ "protein_id": "YP_010377052.1", "aa_start": 1, "aa_end": 166, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "Myristoylated protein E7 (MPOX)", + "uri": "GENEPIO:0101600" + }, + "protein_symbol": { + "label": "Opg069 protein (MPOX)", + "uri": "GENEPIO:0101765" + } }, "gene-NBT03_gp049": { "type": "gene", @@ -1515,7 +2667,23 @@ "gene": "OPG070", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp049", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-054" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-054", + "gene_name": { + "label": "orthopoxvirus gene 070 (MPOX)", + "uri": "GENEPIO:0101255" + }, + "gene_symbol": { + "label": "opg070 gene (MPOX)", + "uri": "GENEPIO:0101430" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp056": { "type": "CDS", @@ -1533,7 +2701,15 @@ "protein_id": "YP_010377053.1", "aa_start": 1, "aa_end": 273, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "Membrane protein E8 (MPOX)", + "uri": "GENEPIO:0101601" + }, + "protein_symbol": { + "label": "Opg070 protein (MPOX)", + "uri": "GENEPIO:0101766" + } }, "gene-NBT03_gp050": { "type": "gene", @@ -1546,7 +2722,23 @@ "gene": "OPG071", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp050", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-055" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-055", + "gene_name": { + "label": "orthopoxvirus gene 071 (MPOX)", + "uri": "GENEPIO:0101256" + }, + "gene_symbol": { + "label": "opg071 gene (MPOX)", + "uri": "GENEPIO:0101431" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp057": { "type": "CDS", @@ -1564,7 +2756,15 @@ "protein_id": "YP_010377054.1", "aa_start": 1, "aa_end": 1006, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "DNA polymerase (2) protein (MPOX)", + "uri": "GENEPIO:0101602" + }, + "protein_symbol": { + "label": "Opg071 protein (MPOX)", + "uri": "GENEPIO:0101767" + } }, "gene-NBT03_gp051": { "type": "gene", @@ -1577,7 +2777,23 @@ "gene": "OPG072", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp051", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-056" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-056", + "gene_name": { + "label": "orthopoxvirus gene 072 (MPOX)", + "uri": "GENEPIO:0101257" + }, + "gene_symbol": { + "label": "opg072 gene (MPOX)", + "uri": "GENEPIO:0101432" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp058": { "type": "CDS", @@ -1595,7 +2811,15 @@ "protein_id": "YP_010377055.1", "aa_start": 1, "aa_end": 95, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Sulfhydryl oxidase protein (MPOX)", + "uri": "GENEPIO:0101603" + }, + "protein_symbol": { + "label": "Opg072 protein (MPOX)", + "uri": "GENEPIO:0101768" + } }, "gene-NBT03_gp052": { "type": "gene", @@ -1607,7 +2831,23 @@ "gbkey": "Gene", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp052", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-057" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-057", + "gene_name": { + "label": "orthopoxvirus gene 073 (MPOX)", + "uri": "GENEPIO:0101258" + }, + "gene_symbol": { + "label": "opg073 gene (MPOX)", + "uri": "GENEPIO:0101433" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp059": { "type": "CDS", @@ -1624,7 +2864,15 @@ "protein_id": "YP_010377056.1", "aa_start": 1, "aa_end": 129, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "Virion core protein E11 (MPOX)", + "uri": "GENEPIO:0101604" + }, + "protein_symbol": { + "label": "Opg073 protein (MPOX)", + "uri": "GENEPIO:0101769" + } }, "gene-NBT03_gp053": { "type": "gene", @@ -1637,7 +2885,23 @@ "gene": "OPG074", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp053", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-058" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-058", + "gene_name": { + "label": "orthopoxvirus gene 074 (MPOX)", + "uri": "GENEPIO:0101259" + }, + "gene_symbol": { + "label": "opg074 gene (MPOX)", + "uri": "GENEPIO:0101434" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp060": { "type": "CDS", @@ -1655,7 +2919,15 @@ "protein_id": "YP_010377057.1", "aa_start": 1, "aa_end": 665, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "Iev morphogenesis protein (MPOX)", + "uri": "GENEPIO:0101596" + }, + "protein_symbol": { + "label": "Opg074 protein (MPOX)", + "uri": "GENEPIO:0101770" + } }, "gene-NBT03_gp054": { "type": "gene", @@ -1668,7 +2940,23 @@ "gene": "OPG075", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp054", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-059" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-059", + "gene_name": { + "label": "orthopoxvirus gene 075 (MPOX)", + "uri": "GENEPIO:0101260" + }, + "gene_symbol": { + "label": "opg075 gene (MPOX)", + "uri": "GENEPIO:0101435" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp061": { "type": "CDS", @@ -1686,7 +2974,15 @@ "protein_id": "YP_010377058.1", "aa_start": 1, "aa_end": 108, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "Glutaredoxin-1 protein (MPOX)", + "uri": "GENEPIO:0101605" + }, + "protein_symbol": { + "label": "Opg075 protein (MPOX)", + "uri": "GENEPIO:0101771" + } }, "gene-NBT03_gp055": { "type": "gene", @@ -1698,7 +2994,23 @@ "gbkey": "Gene", "gene": "OPG076", "gene_biotype": "protein_coding", - "locus_tag": "NBT03_gp055" + "locus_tag": "NBT03_gp055", + "gene_name": { + "label": "orthopoxvirus gene 075 (MPOX)", + "uri": "GENEPIO:0101260" + }, + "gene_symbol": { + "label": "opg075 gene (MPOX)", + "uri": "GENEPIO:0101435" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MV membrane%2C EFC component": { "type": "CDS", @@ -1715,7 +3027,15 @@ "protein_id": "YP_010377183.1", "aa_start": 1, "aa_end": 35, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Glutaredoxin-1 protein (MPOX)", + "uri": "GENEPIO:0101605" + }, + "protein_symbol": { + "label": "Opg075 protein (MPOX)", + "uri": "GENEPIO:0101771" + } }, "gene-NBT03_gp056": { "type": "gene", @@ -1728,7 +3048,23 @@ "gene": "OPG077", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp056", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-060" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-060", + "gene_name": { + "label": "orthopoxvirus gene 077 (MPOX)", + "uri": "GENEPIO:0101262" + }, + "gene_symbol": { + "label": "opg077 gene (MPOX)", + "uri": "GENEPIO:0101437" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp062": { "type": "CDS", @@ -1746,7 +3082,15 @@ "protein_id": "YP_010377059.1", "aa_start": 1, "aa_end": 312, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "Telomere-binding protein I1 (MPOX)", + "uri": "GENEPIO:0101607" + }, + "protein_symbol": { + "label": "Opg077 protein (MPOX)", + "uri": "GENEPIO:0101772" + } }, "gene-NBT03_gp057": { "type": "gene", @@ -1759,7 +3103,23 @@ "gene": "OPG078", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp057", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-061" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-061", + "gene_name": { + "label": "orthopoxvirus gene 078 (MPOX)", + "uri": "GENEPIO:0101263" + }, + "gene_symbol": { + "label": "opg078 gene (MPOX)", + "uri": "GENEPIO:0101438" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp063": { "type": "CDS", @@ -1777,7 +3137,15 @@ "protein_id": "YP_010377060.1", "aa_start": 1, "aa_end": 73, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "IMV membrane protein I2 (MPOX)", + "uri": "GENEPIO:0101608" + }, + "protein_symbol": { + "label": "Opg078 protein (MPOX)", + "uri": "GENEPIO:0101773" + } }, "gene-NBT03_gp058": { "type": "gene", @@ -1790,7 +3158,23 @@ "gene": "OPG079", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp058", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-062" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-062", + "gene_name": { + "label": "orthopoxvirus gene 079 (MPOX)", + "uri": "GENEPIO:0101264" + }, + "gene_symbol": { + "label": "opg079 gene (MPOX)", + "uri": "GENEPIO:0101439" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp064": { "type": "CDS", @@ -1808,7 +3192,15 @@ "protein_id": "YP_010377061.1", "aa_start": 1, "aa_end": 269, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "DNA-binding phosphoprotein (2) (MPOX)", + "uri": "GENEPIO:0101609" + }, + "protein_symbol": { + "label": "Opg079 protein (MPOX)", + "uri": "GENEPIO:0101774" + } }, "gene-NBT03_gp059": { "type": "gene", @@ -1821,7 +3213,23 @@ "gene": "OPG080", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp059", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-063" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-063", + "gene_name": { + "label": "orthopoxvirus gene 080 (MPOX)", + "uri": "GENEPIO:0101265" + }, + "gene_symbol": { + "label": "opg080 gene (MPOX)", + "uri": "GENEPIO:0101440" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp065": { "type": "CDS", @@ -1839,7 +3247,15 @@ "protein_id": "YP_010377062.1", "aa_start": 1, "aa_end": 771, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "Ribonucleoside-diphosphate reductase (2) protein (MPOX)", + "uri": "GENEPIO:0101610" + }, + "protein_symbol": { + "label": "Opg080 protein (MPOX)", + "uri": "GENEPIO:0101775" + } }, "gene-NBT03_gp060": { "type": "gene", @@ -1852,7 +3268,23 @@ "gene": "OPG081", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp060", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-064" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-064", + "gene_name": { + "label": "orthopoxvirus gene 081 (MPOX)", + "uri": "GENEPIO:0101266" + }, + "gene_symbol": { + "label": "opg081 gene (MPOX)", + "uri": "GENEPIO:0101441" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp066": { "type": "CDS", @@ -1870,7 +3302,15 @@ "protein_id": "YP_010377063.1", "aa_start": 1, "aa_end": 79, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "IMV membrane protein I5 (MPOX)", + "uri": "GENEPIO:0101611" + }, + "protein_symbol": { + "label": "Opg081 protein (MPOX)", + "uri": "GENEPIO:0101776" + } }, "gene-NBT03_gp061": { "type": "gene", @@ -1883,7 +3323,23 @@ "gene": "OPG082", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp061", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-065" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-065", + "gene_name": { + "label": "orthopoxvirus gene 082 (MPOX)", + "uri": "GENEPIO:0101267" + }, + "gene_symbol": { + "label": "opg082 gene (MPOX)", + "uri": "GENEPIO:0101442" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp067": { "type": "CDS", @@ -1901,7 +3357,15 @@ "protein_id": "YP_010377064.1", "aa_start": 1, "aa_end": 382, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Telomere-binding protein (MPOX)", + "uri": "GENEPIO:0101612" + }, + "protein_symbol": { + "label": "Opg082 protein (MPOX)", + "uri": "GENEPIO:0101777" + } }, "gene-NBT03_gp062": { "type": "gene", @@ -1914,7 +3378,23 @@ "gene": "OPG083", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp062", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-066" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-066", + "gene_name": { + "label": "orthopoxvirus gene 083 (MPOX)", + "uri": "GENEPIO:0101268" + }, + "gene_symbol": { + "label": "opg083 gene (MPOX)", + "uri": "GENEPIO:0101443" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp068": { "type": "CDS", @@ -1932,7 +3412,15 @@ "protein_id": "YP_010377065.1", "aa_start": 1, "aa_end": 423, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "Viral core cysteine proteinase (MPOX)", + "uri": "GENEPIO:0101613" + }, + "protein_symbol": { + "label": "Opg083 protein (MPOX)", + "uri": "GENEPIO:0101778" + } }, "gene-NBT03_gp063": { "type": "gene", @@ -1945,7 +3433,23 @@ "gene": "OPG084", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp063", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-067" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-067", + "gene_name": { + "label": "orthopoxvirus gene 084 (MPOX)", + "uri": "GENEPIO:0101269" + }, + "gene_symbol": { + "label": "opg084 gene (MPOX)", + "uri": "GENEPIO:0101444" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp069": { "type": "CDS", @@ -1963,7 +3467,15 @@ "protein_id": "YP_010377066.1", "aa_start": 1, "aa_end": 676, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "RNA helicase NPH-II (2) protein (MPOX)", + "uri": "GENEPIO:0101614" + }, + "protein_symbol": { + "label": "Opg084 protein (MPOX)", + "uri": "GENEPIO:0101779" + } }, "gene-NBT03_gp064": { "type": "gene", @@ -1976,7 +3488,23 @@ "gene": "OPG085", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp064", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-068" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-068", + "gene_name": { + "label": "orthopoxvirus gene 085 (MPOX)", + "uri": "GENEPIO:0101270" + }, + "gene_symbol": { + "label": "opg085 gene (MPOX)", + "uri": "GENEPIO:0101445" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp070": { "type": "CDS", @@ -1994,7 +3522,15 @@ "protein_id": "YP_010377067.1", "aa_start": 1, "aa_end": 591, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "Metalloendopeptidase protein (MPOX)", + "uri": "GENEPIO:0101615" + }, + "protein_symbol": { + "label": "Opg085 protein (MPOX)", + "uri": "GENEPIO:0101780" + } }, "gene-NBT03_gp065": { "type": "gene", @@ -2007,7 +3543,23 @@ "gene": "OPG086", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp065", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-069" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-069", + "gene_name": { + "label": "orthopoxvirus gene 086 (MPOX)", + "uri": "GENEPIO:0101271" + }, + "gene_symbol": { + "label": "opg086 gene (MPOX)", + "uri": "GENEPIO:0101446" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp071": { "type": "CDS", @@ -2025,7 +3577,15 @@ "protein_id": "YP_010377068.1", "aa_start": 1, "aa_end": 111, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Entry/fusion complex component protein (MPOX)", + "uri": "GENEPIO:0101616" + }, + "protein_symbol": { + "label": "Opg086 protein (MPOX)", + "uri": "GENEPIO:0101781" + } }, "gene-NBT03_gp066": { "type": "gene", @@ -2038,7 +3598,23 @@ "gene": "OPG087", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp066", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-070" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-070", + "gene_name": { + "label": "orthopoxvirus gene 087 (MPOX)", + "uri": "GENEPIO:0101272" + }, + "gene_symbol": { + "label": "opg087 gene (MPOX)", + "uri": "GENEPIO:0101447" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp072": { "type": "CDS", @@ -2056,7 +3632,15 @@ "protein_id": "YP_010377069.1", "aa_start": 1, "aa_end": 220, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "Late transcription elongation factor protein (MPOX)", + "uri": "GENEPIO:0101617" + }, + "protein_symbol": { + "label": "Opg087 protein (MPOX)", + "uri": "GENEPIO:0101782" + } }, "gene-NBT03_gp067": { "type": "gene", @@ -2069,7 +3653,23 @@ "gene": "OPG088", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp067", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-071" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-071", + "gene_name": { + "label": "orthopoxvirus gene 088 (MPOX)", + "uri": "GENEPIO:0101273" + }, + "gene_symbol": { + "label": "opg088 gene (MPOX)", + "uri": "GENEPIO:0101448" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp073": { "type": "CDS", @@ -2087,7 +3687,15 @@ "protein_id": "YP_010377070.1", "aa_start": 1, "aa_end": 124, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "Glutaredoxin-2 protein (MPOX)", + "uri": "GENEPIO:0101618" + }, + "protein_symbol": { + "label": "Opg088 protein (MPOX)", + "uri": "GENEPIO:0101783" + } }, "gene-NBT03_gp068": { "type": "gene", @@ -2100,7 +3708,23 @@ "gene": "OPG089", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp068", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-072" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-072", + "gene_name": { + "label": "orthopoxvirus gene 089 (MPOX)", + "uri": "GENEPIO:0101274" + }, + "gene_symbol": { + "label": "opg089 gene (MPOX)", + "uri": "GENEPIO:0101449" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp074": { "type": "CDS", @@ -2118,7 +3742,15 @@ "protein_id": "YP_010377071.1", "aa_start": 1, "aa_end": 434, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "FEN1-like nuclease protein (MPOX)", + "uri": "GENEPIO:0101619" + }, + "protein_symbol": { + "label": "Opg089 protein (MPOX)", + "uri": "GENEPIO:0101784" + } }, "gene-NBT03_gp069": { "type": "gene", @@ -2131,7 +3763,23 @@ "gene": "OPG090", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp069", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-073" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-073", + "gene_name": { + "label": "orthopoxvirus gene 090 (MPOX)", + "uri": "GENEPIO:0101275" + }, + "gene_symbol": { + "label": "opg090 gene (MPOX)", + "uri": "GENEPIO:0101450" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp075": { "type": "CDS", @@ -2149,7 +3797,15 @@ "protein_id": "YP_010377072.1", "aa_start": 1, "aa_end": 63, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "DNA-directed RNA polymerase 7 kDa subunit protein (MPOX)", + "uri": "GENEPIO:0101620" + }, + "protein_symbol": { + "label": "Opg090 protein (MPOX)", + "uri": "GENEPIO:0101785" + } }, "gene-NBT03_gp070": { "type": "gene", @@ -2162,7 +3818,23 @@ "gene": "OPG091", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp070", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-074" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-074", + "gene_name": { + "label": "orthopoxvirus gene 091 (MPOX)", + "uri": "GENEPIO:0101276" + }, + "gene_symbol": { + "label": "opg091 gene (MPOX)", + "uri": "GENEPIO:0101451" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp076": { "type": "CDS", @@ -2180,7 +3852,15 @@ "protein_id": "YP_010377073.1", "aa_start": 1, "aa_end": 165, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "Nlpc/p60 superfamily protein (MPOX)", + "uri": "GENEPIO:0101621" + }, + "protein_symbol": { + "label": "Opg091 protein (MPOX)", + "uri": "GENEPIO:0101786" + } }, "gene-NBT03_gp071": { "type": "gene", @@ -2193,7 +3873,23 @@ "gene": "OPG092", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp071", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-075" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-075", + "gene_name": { + "label": "orthopoxvirus gene 092 (MPOX)", + "uri": "GENEPIO:0101277" + }, + "gene_symbol": { + "label": "opg092 gene (MPOX)", + "uri": "GENEPIO:0101452" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp077": { "type": "CDS", @@ -2211,7 +3907,15 @@ "protein_id": "YP_010377074.1", "aa_start": 1, "aa_end": 371, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Assembly protein G7 (MPOX)", + "uri": "GENEPIO:0101622" + }, + "protein_symbol": { + "label": "Opg092 protein (MPOX)", + "uri": "GENEPIO:0101787" + } }, "gene-NBT03_gp072": { "type": "gene", @@ -2224,7 +3928,23 @@ "gene": "OPG093", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp072", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-076" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-076", + "gene_name": { + "label": "orthopoxvirus gene 093 (MPOX)", + "uri": "GENEPIO:0101278" + }, + "gene_symbol": { + "label": "opg093 gene (MPOX)", + "uri": "GENEPIO:0101453" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp078": { "type": "CDS", @@ -2242,7 +3962,15 @@ "protein_id": "YP_010377075.1", "aa_start": 1, "aa_end": 260, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "Late transcription factor VLTF-1 protein (MPOX)", + "uri": "GENEPIO:0101623" + }, + "protein_symbol": { + "label": "Opg093 protein (MPOX)", + "uri": "GENEPIO:0101788" + } }, "gene-NBT03_gp073": { "type": "gene", @@ -2255,7 +3983,23 @@ "gene": "OPG094", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp073", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-077" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-077", + "gene_name": { + "label": "orthopoxvirus gene 094 (MPOX)", + "uri": "GENEPIO:0101279" + }, + "gene_symbol": { + "label": "opg094 gene (MPOX)", + "uri": "GENEPIO:0101454" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp079": { "type": "CDS", @@ -2273,7 +4017,15 @@ "protein_id": "YP_010377076.1", "aa_start": 1, "aa_end": 340, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "Myristylated protein (MPOX)", + "uri": "GENEPIO:0101624" + }, + "protein_symbol": { + "label": "Opg094 protein (MPOX)", + "uri": "GENEPIO:0101789" + } }, "gene-NBT03_gp074": { "type": "gene", @@ -2286,7 +4038,23 @@ "gene": "OPG095", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp074", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-078" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-078", + "gene_name": { + "label": "orthopoxvirus gene 095 (MPOX)", + "uri": "GENEPIO:0101280" + }, + "gene_symbol": { + "label": "opg095 gene (MPOX)", + "uri": "GENEPIO:0101455" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp080": { "type": "CDS", @@ -2304,7 +4072,15 @@ "protein_id": "YP_010377077.1", "aa_start": 1, "aa_end": 250, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "IMV membrane protein L1R (MPOX)", + "uri": "GENEPIO:0101585" + }, + "protein_symbol": { + "label": "Opg095 protein (MPOX)", + "uri": "GENEPIO:0101790" + } }, "gene-NBT03_gp075": { "type": "gene", @@ -2317,7 +4093,23 @@ "gene": "OPG096", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp075", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-079" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-079", + "gene_name": { + "label": "orthopoxvirus gene 096 (MPOX)", + "uri": "GENEPIO:0101281" + }, + "gene_symbol": { + "label": "opg096 gene (MPOX)", + "uri": "GENEPIO:0101456" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp081": { "type": "CDS", @@ -2335,7 +4127,15 @@ "protein_id": "YP_010377078.1", "aa_start": 1, "aa_end": 92, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Crescent membrane and immature virion formation protein (MPOX)", + "uri": "GENEPIO:0101625" + }, + "protein_symbol": { + "label": "Opg096 protein (MPOX)", + "uri": "GENEPIO:0101791" + } }, "gene-NBT03_gp076": { "type": "gene", @@ -2348,7 +4148,23 @@ "gene": "OPG097", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp076", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-080" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-080", + "gene_name": { + "label": "orthopoxvirus gene 097 (MPOX)", + "uri": "GENEPIO:0101282" + }, + "gene_symbol": { + "label": "opg097 gene (MPOX)", + "uri": "GENEPIO:0101457" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp082": { "type": "CDS", @@ -2366,7 +4182,15 @@ "protein_id": "YP_010377079.1", "aa_start": 1, "aa_end": 344, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "Internal virion L3/FP4 protein (MPOX)", + "uri": "GENEPIO:0101626" + }, + "protein_symbol": { + "label": "Opg097 protein (MPOX)", + "uri": "GENEPIO:0101792" + } }, "gene-NBT03_gp077": { "type": "gene", @@ -2379,7 +4203,23 @@ "gene": "OPG098", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp077", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-081" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-081", + "gene_name": { + "label": "orthopoxvirus gene 098 (MPOX)", + "uri": "GENEPIO:0101283" + }, + "gene_symbol": { + "label": "opg098 gene (MPOX)", + "uri": "GENEPIO:0101458" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp083": { "type": "CDS", @@ -2397,7 +4237,15 @@ "protein_id": "YP_010377080.1", "aa_start": 1, "aa_end": 251, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "Nucleic acid binding protein VP8/L4R (MPOX)", + "uri": "GENEPIO:0101627" + }, + "protein_symbol": { + "label": "Opg098 protein (MPOX)", + "uri": "GENEPIO:0101793" + } }, "gene-NBT03_gp078": { "type": "gene", @@ -2410,7 +4258,23 @@ "gene": "OPG099", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp078", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-082" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-082", + "gene_name": { + "label": "orthopoxvirus gene 099 (MPOX)", + "uri": "GENEPIO:0101284" + }, + "gene_symbol": { + "label": "opg099 gene (MPOX)", + "uri": "GENEPIO:0101459" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp084": { "type": "CDS", @@ -2428,7 +4292,15 @@ "protein_id": "YP_010377081.1", "aa_start": 1, "aa_end": 128, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "Membrane protein CL5 (MPOX)", + "uri": "GENEPIO:0101628" + }, + "protein_symbol": { + "label": "Opg099 protein (MPOX)", + "uri": "GENEPIO:0101794" + } }, "gene-NBT03_gp079": { "type": "gene", @@ -2441,7 +4313,23 @@ "gene": "OPG100", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp079", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-083" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-083", + "gene_name": { + "label": "orthopoxvirus gene 100 (MPOX)", + "uri": "GENEPIO:0101285" + }, + "gene_symbol": { + "label": "opg100 gene (MPOX)", + "uri": "GENEPIO:0101460" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp085": { "type": "CDS", @@ -2459,7 +4347,15 @@ "protein_id": "YP_010377082.1", "aa_start": 1, "aa_end": 152, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "IMV membrane protein J1 (MPOX)", + "uri": "GENEPIO:0101629" + }, + "protein_symbol": { + "label": "Opg100 protein (MPOX)", + "uri": "GENEPIO:0101795" + } }, "gene-NBT03_gp080": { "type": "gene", @@ -2472,7 +4368,23 @@ "gene": "OPG101", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp080", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-084" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-084", + "gene_name": { + "label": "orthopoxvirus gene 101 (MPOX)", + "uri": "GENEPIO:0101286" + }, + "gene_symbol": { + "label": "opg101 gene (MPOX)", + "uri": "GENEPIO:0101461" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp086": { "type": "CDS", @@ -2490,7 +4402,15 @@ "protein_id": "YP_010377083.1", "aa_start": 1, "aa_end": 177, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "Thymidine kinase protein (MPOX)", + "uri": "GENEPIO:0101630" + }, + "protein_symbol": { + "label": "Opg101 protein (MPOX)", + "uri": "GENEPIO:0101796" + } }, "gene-NBT03_gp081": { "type": "gene", @@ -2503,7 +4423,23 @@ "gene": "OPG102", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp081", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-085" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-085", + "gene_name": { + "label": "orthopoxvirus gene 102 (MPOX)", + "uri": "GENEPIO:0101287" + }, + "gene_symbol": { + "label": "opg102 gene (MPOX)", + "uri": "GENEPIO:0101462" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp087": { "type": "CDS", @@ -2521,7 +4457,15 @@ "protein_id": "YP_010377084.1", "aa_start": 1, "aa_end": 333, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Cap-specific mRNA protein (MPOX)", + "uri": "GENEPIO:0101631" + }, + "protein_symbol": { + "label": "Opg102 protein (MPOX)", + "uri": "GENEPIO:0101797" + } }, "gene-NBT03_gp082": { "type": "gene", @@ -2534,7 +4478,23 @@ "gene": "OPG103", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp082", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-086" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-086", + "gene_name": { + "label": "orthopoxvirus gene 103 (MPOX)", + "uri": "GENEPIO:0101288" + }, + "gene_symbol": { + "label": "opg103 gene (MPOX)", + "uri": "GENEPIO:0101463" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp088": { "type": "CDS", @@ -2552,7 +4512,15 @@ "protein_id": "YP_010377085.1", "aa_start": 1, "aa_end": 185, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "DNA-directed RNA polymerase subunit protein (MPOX)", + "uri": "GENEPIO:0101632" + }, + "protein_symbol": { + "label": "Opg103 protein (MPOX)", + "uri": "GENEPIO:0101798" + } }, "gene-NBT03_gp083": { "type": "gene", @@ -2565,7 +4533,23 @@ "gene": "OPG104", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp083", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-087" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-087", + "gene_name": { + "label": "orthopoxvirus gene 104 (MPOX)", + "uri": "GENEPIO:0101289" + }, + "gene_symbol": { + "label": "opg104 gene (MPOX)", + "uri": "GENEPIO:0101464" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp089": { "type": "CDS", @@ -2583,7 +4567,15 @@ "protein_id": "YP_010377086.1", "aa_start": 1, "aa_end": 133, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "Myristylated protein (MPOX)", + "uri": "GENEPIO:0101624" + }, + "protein_symbol": { + "label": "Opg104 protein (MPOX)", + "uri": "GENEPIO:0101799" + } }, "gene-NBT03_gp084": { "type": "gene", @@ -2596,7 +4588,23 @@ "gene": "OPG105", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp084", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-088" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-088", + "gene_name": { + "label": "orthopoxvirus gene 105 (MPOX)", + "uri": "GENEPIO:0101290" + }, + "gene_symbol": { + "label": "opg105 gene (MPOX)", + "uri": "GENEPIO:0101465" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp090": { "type": "CDS", @@ -2614,7 +4622,15 @@ "protein_id": "YP_010377087.1", "aa_start": 1, "aa_end": 1286, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "DNA-dependent RNA polymerase subunit rpo147 protein (MPOX)", + "uri": "GENEPIO:0101633" + }, + "protein_symbol": { + "label": "Opg105 protein (MPOX)", + "uri": "GENEPIO:0101800" + } }, "gene-NBT03_gp085": { "type": "gene", @@ -2627,7 +4643,23 @@ "gene": "OPG106", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp085", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-089" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-089", + "gene_name": { + "label": "orthopoxvirus gene 106 (MPOX)", + "uri": "GENEPIO:0101291" + }, + "gene_symbol": { + "label": "opg106 gene (MPOX)", + "uri": "GENEPIO:0101466" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp091": { "type": "CDS", @@ -2645,7 +4677,15 @@ "protein_id": "YP_010377088.1", "aa_start": 1, "aa_end": 171, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Tyr/ser protein phosphatase (MPOX)", + "uri": "GENEPIO:0101634" + }, + "protein_symbol": { + "label": "Opg106 protein (MPOX)", + "uri": "GENEPIO:0101801" + } }, "gene-NBT03_gp086": { "type": "gene", @@ -2658,7 +4698,23 @@ "gene": "OPG107", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp086", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-090" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-090", + "gene_name": { + "label": "orthopoxvirus gene 107 (MPOX)", + "uri": "GENEPIO:0101292" + }, + "gene_symbol": { + "label": "opg107 gene (MPOX)", + "uri": "GENEPIO:0101467" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp092": { "type": "CDS", @@ -2676,7 +4732,15 @@ "protein_id": "YP_010377089.1", "aa_start": 1, "aa_end": 189, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "Entry-fusion complex essential component protein (MPOX)", + "uri": "GENEPIO:0101635" + }, + "protein_symbol": { + "label": "Opg107 protein (MPOX)", + "uri": "GENEPIO:0101802" + } }, "gene-NBT03_gp087": { "type": "gene", @@ -2689,7 +4753,23 @@ "gene": "OPG108", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp087", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-091" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-091", + "gene_name": { + "label": "orthopoxvirus gene 108 (MPOX)", + "uri": "GENEPIO:0101293" + }, + "gene_symbol": { + "label": "opg108 gene (MPOX)", + "uri": "GENEPIO:0101468" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp093": { "type": "CDS", @@ -2707,7 +4787,15 @@ "protein_id": "YP_010377090.1", "aa_start": 1, "aa_end": 324, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "IMV heparin binding surface protein (MPOX)", + "uri": "GENEPIO:0101636" + }, + "protein_symbol": { + "label": "Opg108 protein (MPOX)", + "uri": "GENEPIO:0101803" + } }, "gene-NBT03_gp088": { "type": "gene", @@ -2720,7 +4808,23 @@ "gene": "OPG109", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp088", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-092" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-092", + "gene_name": { + "label": "orthopoxvirus gene 109 (MPOX)", + "uri": "GENEPIO:0101294" + }, + "gene_symbol": { + "label": "opg109 gene (MPOX)", + "uri": "GENEPIO:0101469" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp094": { "type": "CDS", @@ -2738,7 +4842,15 @@ "protein_id": "YP_010377091.1", "aa_start": 1, "aa_end": 795, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "RNA polymerase-associated transcription-specificity factor RAP94 protein (MPOX)", + "uri": "GENEPIO:0101637" + }, + "protein_symbol": { + "label": "Opg109 protein (MPOX)", + "uri": "GENEPIO:0101804" + } }, "gene-NBT03_gp089": { "type": "gene", @@ -2751,7 +4863,23 @@ "gene": "OPG110", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp089", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-093" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-093", + "gene_name": { + "label": "orthopoxvirus gene 110 (MPOX)", + "uri": "GENEPIO:0101295" + }, + "gene_symbol": { + "label": "opg110 gene (MPOX)", + "uri": "GENEPIO:0101470" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp095": { "type": "CDS", @@ -2769,7 +4897,15 @@ "protein_id": "YP_010377092.1", "aa_start": 1, "aa_end": 210, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "Late transcription factor VLTF-4 (1) protein (MPOX)", + "uri": "GENEPIO:0101638" + }, + "protein_symbol": { + "label": "Opg110 protein (MPOX)", + "uri": "GENEPIO:0101805" + } }, "gene-NBT03_gp090": { "type": "gene", @@ -2782,7 +4918,23 @@ "gene": "OPG111", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp090", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-094" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-094", + "gene_name": { + "label": "orthopoxvirus gene 111 (MPOX)", + "uri": "GENEPIO:0101296" + }, + "gene_symbol": { + "label": "opg111 gene (MPOX)", + "uri": "GENEPIO:0101471" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp096": { "type": "CDS", @@ -2800,7 +4952,15 @@ "protein_id": "YP_010377093.1", "aa_start": 1, "aa_end": 314, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "DNA topoisomerase type I protein (MPOX)", + "uri": "GENEPIO:0101639" + }, + "protein_symbol": { + "label": "Opg111 protein (MPOX)", + "uri": "GENEPIO:0101806" + } }, "gene-NBT03_gp091": { "type": "gene", @@ -2813,7 +4973,23 @@ "gene": "OPG112", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp091", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-095" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-095", + "gene_name": { + "label": "orthopoxvirus gene 112 (MPOX)", + "uri": "GENEPIO:0101297" + }, + "gene_symbol": { + "label": "opg112 gene (MPOX)", + "uri": "GENEPIO:0101472" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp097": { "type": "CDS", @@ -2831,7 +5007,15 @@ "protein_id": "YP_010377094.1", "aa_start": 1, "aa_end": 146, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Late protein H7 (MPOX)", + "uri": "GENEPIO:0101640" + }, + "protein_symbol": { + "label": "Opg112 protein (MPOX)", + "uri": "GENEPIO:0101807" + } }, "gene-NBT03_gp092": { "type": "gene", @@ -2844,7 +5028,23 @@ "gene": "OPG113", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp092", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-096" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-096", + "gene_name": { + "label": "orthopoxvirus gene 113 (MPOX)", + "uri": "GENEPIO:0101298" + }, + "gene_symbol": { + "label": "opg113 gene (MPOX)", + "uri": "GENEPIO:0101473" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp098": { "type": "CDS", @@ -2862,7 +5062,15 @@ "protein_id": "YP_010377095.1", "aa_start": 1, "aa_end": 845, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "mRNA capping enzyme large subunit protein (MPOX)", + "uri": "GENEPIO:0101641" + }, + "protein_symbol": { + "label": "Opg113 protein (MPOX)", + "uri": "GENEPIO:0101808" + } }, "gene-NBT03_gp093": { "type": "gene", @@ -2875,7 +5083,23 @@ "gene": "OPG114", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp093", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-097" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-097", + "gene_name": { + "label": "orthopoxvirus gene 114 (MPOX)", + "uri": "GENEPIO:0101299" + }, + "gene_symbol": { + "label": "opg114 gene (MPOX)", + "uri": "GENEPIO:0101474" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp099": { "type": "CDS", @@ -2893,7 +5117,15 @@ "protein_id": "YP_010377096.1", "aa_start": 1, "aa_end": 146, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "Virion protein D2 (MPOX)", + "uri": "GENEPIO:0101642" + }, + "protein_symbol": { + "label": "Opg114 protein (MPOX)", + "uri": "GENEPIO:0101809" + } }, "gene-NBT03_gp094": { "type": "gene", @@ -2906,7 +5138,23 @@ "gene": "OPG115", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp094", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-098" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-098", + "gene_name": { + "label": "orthopoxvirus gene 115 (MPOX)", + "uri": "GENEPIO:0101300" + }, + "gene_symbol": { + "label": "opg115 gene (MPOX)", + "uri": "GENEPIO:0101475" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp100": { "type": "CDS", @@ -2924,7 +5172,15 @@ "protein_id": "YP_010377097.1", "aa_start": 1, "aa_end": 233, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "Virion core protein D3 (MPOX)", + "uri": "GENEPIO:0101643" + }, + "protein_symbol": { + "label": "Opg115 protein (MPOX)", + "uri": "GENEPIO:0101810" + } }, "gene-NBT03_gp095": { "type": "gene", @@ -2937,7 +5193,23 @@ "gene": "OPG116", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp095", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-099" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-099", + "gene_name": { + "label": "orthopoxvirus gene 116 (MPOX)", + "uri": "GENEPIO:0101301" + }, + "gene_symbol": { + "label": "opg116 gene (MPOX)", + "uri": "GENEPIO:0101476" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp101": { "type": "CDS", @@ -2955,7 +5227,15 @@ "protein_id": "YP_010377098.1", "aa_start": 1, "aa_end": 218, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Uracil DNA glycosylase superfamily protein (MPOX)", + "uri": "GENEPIO:0101644" + }, + "protein_symbol": { + "label": "Opg116 protein (MPOX)", + "uri": "GENEPIO:0101811" + } }, "gene-NBT03_gp096": { "type": "gene", @@ -2968,7 +5248,23 @@ "gene": "OPG117", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp096", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-100" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-100", + "gene_name": { + "label": "orthopoxvirus gene 117 (MPOX)", + "uri": "GENEPIO:0101302" + }, + "gene_symbol": { + "label": "opg117 gene (MPOX)", + "uri": "GENEPIO:0101477" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp102": { "type": "CDS", @@ -2986,7 +5282,15 @@ "protein_id": "YP_010377099.1", "aa_start": 1, "aa_end": 785, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "NTPase (1) protein (MPOX)", + "uri": "GENEPIO:0101645" + }, + "protein_symbol": { + "label": "Opg117 protein (MPOX)", + "uri": "GENEPIO:0101812" + } }, "gene-NBT03_gp097": { "type": "gene", @@ -2999,7 +5303,23 @@ "gene": "OPG118", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp097", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-101" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-101", + "gene_name": { + "label": "orthopoxvirus gene 118 (MPOX)", + "uri": "GENEPIO:0101303" + }, + "gene_symbol": { + "label": "opg118 gene (MPOX)", + "uri": "GENEPIO:0101478" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp103": { "type": "CDS", @@ -3017,7 +5337,15 @@ "protein_id": "YP_010377100.1", "aa_start": 1, "aa_end": 637, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "Early transcription factor 70 kDa subunit protein (MPOX)", + "uri": "GENEPIO:0101646" + }, + "protein_symbol": { + "label": "Opg118 protein (MPOX)", + "uri": "GENEPIO:0101813" + } }, "gene-NBT03_gp098": { "type": "gene", @@ -3030,7 +5358,23 @@ "gene": "OPG119", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp098", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-102" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-102", + "gene_name": { + "label": "orthopoxvirus gene 119 (MPOX)", + "uri": "GENEPIO:0101304" + }, + "gene_symbol": { + "label": "opg119 gene (MPOX)", + "uri": "GENEPIO:0101479" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp104": { "type": "CDS", @@ -3048,7 +5392,15 @@ "protein_id": "YP_010377101.1", "aa_start": 1, "aa_end": 161, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "RNA polymerase subunit RPO18 protein (MPOX)", + "uri": "GENEPIO:0101647" + }, + "protein_symbol": { + "label": "Opg119 protein (MPOX)", + "uri": "GENEPIO:0101814" + } }, "gene-NBT03_gp099": { "type": "gene", @@ -3061,7 +5413,23 @@ "gene": "OPG120", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp099", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-103" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-103", + "gene_name": { + "label": "orthopoxvirus gene 120 (MPOX)", + "uri": "GENEPIO:0101305" + }, + "gene_symbol": { + "label": "opg120 gene (MPOX)", + "uri": "GENEPIO:0101480" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp105": { "type": "CDS", @@ -3079,7 +5447,15 @@ "protein_id": "YP_010377102.1", "aa_start": 1, "aa_end": 304, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "Carbonic anhydrase protein (MPOX)", + "uri": "GENEPIO:0101648" + }, + "protein_symbol": { + "label": "Opg120 protein (MPOX)", + "uri": "GENEPIO:0101815" + } }, "gene-NBT03_gp100": { "type": "gene", @@ -3092,7 +5468,23 @@ "gene": "OPG121", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp100", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-104" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-104", + "gene_name": { + "label": "orthopoxvirus gene 121 (MPOX)", + "uri": "GENEPIO:0101306" + }, + "gene_symbol": { + "label": "opg121 gene (MPOX)", + "uri": "GENEPIO:0101481" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp106": { "type": "CDS", @@ -3110,7 +5502,15 @@ "protein_id": "YP_010377103.1", "aa_start": 1, "aa_end": 213, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "NUDIX domain protein (MPOX)", + "uri": "GENEPIO:0101649" + }, + "protein_symbol": { + "label": "Opg121 protein (MPOX)", + "uri": "GENEPIO:0101816" + } }, "gene-NBT03_gp101": { "type": "gene", @@ -3123,7 +5523,23 @@ "gene": "OPG122", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp101", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-105" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-105", + "gene_name": { + "label": "orthopoxvirus gene 122 (MPOX)", + "uri": "GENEPIO:0101307" + }, + "gene_symbol": { + "label": "opg122 gene (MPOX)", + "uri": "GENEPIO:0101482" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp107": { "type": "CDS", @@ -3141,7 +5557,15 @@ "protein_id": "YP_010377104.1", "aa_start": 1, "aa_end": 248, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "MutT motif protein (MPOX)", + "uri": "GENEPIO:0101650" + }, + "protein_symbol": { + "label": "Opg122 protein (MPOX)", + "uri": "GENEPIO:0101817" + } }, "gene-NBT03_gp102": { "type": "gene", @@ -3154,7 +5578,23 @@ "gene": "OPG123", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp102", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-106" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-106", + "gene_name": { + "label": "orthopoxvirus gene 123 (MPOX)", + "uri": "GENEPIO:0101308" + }, + "gene_symbol": { + "label": "opg123 gene (MPOX)", + "uri": "GENEPIO:0101483" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp108": { "type": "CDS", @@ -3172,7 +5612,15 @@ "protein_id": "YP_010377105.1", "aa_start": 1, "aa_end": 631, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "Nucleoside triphosphatase I protein (MPOX)", + "uri": "GENEPIO:0101651" + }, + "protein_symbol": { + "label": "Opg123 protein (MPOX)", + "uri": "GENEPIO:0101818" + } }, "gene-NBT03_gp103": { "type": "gene", @@ -3185,7 +5633,23 @@ "gene": "OPG124", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp103", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-107" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-107", + "gene_name": { + "label": "orthopoxvirus gene 124 (MPOX)", + "uri": "GENEPIO:0101309" + }, + "gene_symbol": { + "label": "opg124 gene (MPOX)", + "uri": "GENEPIO:0101484" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp109": { "type": "CDS", @@ -3203,7 +5667,15 @@ "protein_id": "YP_010377106.1", "aa_start": 1, "aa_end": 287, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "mRNA capping enzyme small subunit protein (MPOX)", + "uri": "GENEPIO:0101652" + }, + "protein_symbol": { + "label": "Opg124 protein (MPOX)", + "uri": "GENEPIO:0101819" + } }, "gene-NBT03_gp104": { "type": "gene", @@ -3216,7 +5688,23 @@ "gene": "OPG125", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp104", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-108" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-108", + "gene_name": { + "label": "orthopoxvirus gene 125 (MPOX)", + "uri": "GENEPIO:0101310" + }, + "gene_symbol": { + "label": "opg125 gene (MPOX)", + "uri": "GENEPIO:0101485" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp110": { "type": "CDS", @@ -3234,7 +5722,15 @@ "protein_id": "YP_010377107.1", "aa_start": 1, "aa_end": 551, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "Rifampicin resistance protein (MPOX)", + "uri": "GENEPIO:0101653" + }, + "protein_symbol": { + "label": "Opg125 protein (MPOX)", + "uri": "GENEPIO:0101820" + } }, "gene-NBT03_gp105": { "type": "gene", @@ -3247,7 +5743,23 @@ "gene": "OPG126", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp105", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-109" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-109", + "gene_name": { + "label": "orthopoxvirus gene 126 (MPOX)", + "uri": "GENEPIO:0101311" + }, + "gene_symbol": { + "label": "opg126 gene (MPOX)", + "uri": "GENEPIO:0101486" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp111": { "type": "CDS", @@ -3265,7 +5777,15 @@ "protein_id": "YP_010377108.1", "aa_start": 1, "aa_end": 150, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Late transcription factor VLTF-2 (2) protein (MPOX)", + "uri": "GENEPIO:0101654" + }, + "protein_symbol": { + "label": "Opg126 protein (MPOX)", + "uri": "GENEPIO:0101821" + } }, "gene-NBT03_gp106": { "type": "gene", @@ -3278,7 +5798,23 @@ "gene": "OPG127", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp106", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-110" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-110", + "gene_name": { + "label": "orthopoxvirus gene 127 (MPOX)", + "uri": "GENEPIO:0101312" + }, + "gene_symbol": { + "label": "opg127 gene (MPOX)", + "uri": "GENEPIO:0101487" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp112": { "type": "CDS", @@ -3296,7 +5832,15 @@ "protein_id": "YP_010377109.1", "aa_start": 1, "aa_end": 224, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "Late transcription factor VLTF-3 (1) protein (MPOX)", + "uri": "GENEPIO:0101655" + }, + "protein_symbol": { + "label": "Opg127 protein (MPOX)", + "uri": "GENEPIO:0101822" + } }, "gene-NBT03_gp107": { "type": "gene", @@ -3309,7 +5853,23 @@ "gene": "OPG128", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp107", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-111" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-111", + "gene_name": { + "label": "orthopoxvirus gene 128 (MPOX)", + "uri": "GENEPIO:0101313" + }, + "gene_symbol": { + "label": "opg128 gene (MPOX)", + "uri": "GENEPIO:0101488" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp113": { "type": "CDS", @@ -3327,7 +5887,15 @@ "protein_id": "YP_010377110.1", "aa_start": 1, "aa_end": 77, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "S-S bond formation pathway protein (MPOX)", + "uri": "GENEPIO:0101656" + }, + "protein_symbol": { + "label": "Opg128 protein (MPOX)", + "uri": "GENEPIO:0101823" + } }, "gene-NBT03_gp108": { "type": "gene", @@ -3340,7 +5908,23 @@ "gene": "OPG129", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp108", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-112" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-112", + "gene_name": { + "label": "orthopoxvirus gene 129 (MPOX)", + "uri": "GENEPIO:0101314" + }, + "gene_symbol": { + "label": "opg129 gene (MPOX)", + "uri": "GENEPIO:0101489" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp114": { "type": "CDS", @@ -3358,7 +5942,15 @@ "protein_id": "YP_010377111.1", "aa_start": 1, "aa_end": 644, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "Virion core protein P4b (MPOX)", + "uri": "GENEPIO:0101657" + }, + "protein_symbol": { + "label": "Opg129 protein (MPOX)", + "uri": "GENEPIO:0101824" + } }, "gene-NBT03_gp109": { "type": "gene", @@ -3371,7 +5963,23 @@ "gene": "OPG130", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp109", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-113" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-113", + "gene_name": { + "label": "orthopoxvirus gene 130 (MPOX)", + "uri": "GENEPIO:0101315" + }, + "gene_symbol": { + "label": "opg130 gene (MPOX)", + "uri": "GENEPIO:0101490" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp115": { "type": "CDS", @@ -3389,7 +5997,15 @@ "protein_id": "YP_010377112.1", "aa_start": 1, "aa_end": 281, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "A5L protein-like (MPOX)", + "uri": "GENEPIO:0101658" + }, + "protein_symbol": { + "label": "Opg130 protein (MPOX)", + "uri": "GENEPIO:0101825" + } }, "gene-NBT03_gp110": { "type": "gene", @@ -3402,7 +6018,23 @@ "gene": "OPG131", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp110", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-114" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-114", + "gene_name": { + "label": "orthopoxvirus gene 131 (MPOX)", + "uri": "GENEPIO:0101316" + }, + "gene_symbol": { + "label": "opg131 gene (MPOX)", + "uri": "GENEPIO:0101491" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp116": { "type": "CDS", @@ -3420,7 +6052,15 @@ "protein_id": "YP_010377113.1", "aa_start": 1, "aa_end": 161, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "DNA-directed RNA polymerase 19 kDa subunit protein (MPOX)", + "uri": "GENEPIO:0101659" + }, + "protein_symbol": { + "label": "Opg131 protein (MPOX)", + "uri": "GENEPIO:0101826" + } }, "gene-NBT03_gp111": { "type": "gene", @@ -3433,7 +6073,23 @@ "gene": "OPG132", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp111", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-115" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-115", + "gene_name": { + "label": "orthopoxvirus gene 132 (MPOX)", + "uri": "GENEPIO:0101317" + }, + "gene_symbol": { + "label": "opg132 gene (MPOX)", + "uri": "GENEPIO:0101492" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp117": { "type": "CDS", @@ -3451,7 +6107,15 @@ "protein_id": "YP_010377114.1", "aa_start": 1, "aa_end": 372, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Virion morphogenesis protein (MPOX)", + "uri": "GENEPIO:0101660" + }, + "protein_symbol": { + "label": "Opg132 protein (MPOX)", + "uri": "GENEPIO:0101827" + } }, "gene-NBT03_gp112": { "type": "gene", @@ -3464,7 +6128,23 @@ "gene": "OPG133", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp112", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-116" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-116", + "gene_name": { + "label": "orthopoxvirus gene 133 (MPOX)", + "uri": "GENEPIO:0101318" + }, + "gene_symbol": { + "label": "opg133 gene (MPOX)", + "uri": "GENEPIO:0101493" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp118": { "type": "CDS", @@ -3482,7 +6162,15 @@ "protein_id": "YP_010377115.1", "aa_start": 1, "aa_end": 710, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "Early transcription factor 82 kDa subunit protein (MPOX)", + "uri": "GENEPIO:0101661" + }, + "protein_symbol": { + "label": "Opg133 protein (MPOX)", + "uri": "GENEPIO:0101828" + } }, "gene-NBT03_gp113": { "type": "gene", @@ -3495,7 +6183,23 @@ "gene": "OPG134", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp113", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-117" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-117", + "gene_name": { + "label": "orthopoxvirus gene 134 (MPOX)", + "uri": "GENEPIO:0101319" + }, + "gene_symbol": { + "label": "opg134 gene (MPOX)", + "uri": "GENEPIO:0101494" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp119": { "type": "CDS", @@ -3513,7 +6217,15 @@ "protein_id": "YP_010377116.1", "aa_start": 1, "aa_end": 292, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "Intermediate transcription factor VITF-3 (1) protein (MPOX)", + "uri": "GENEPIO:0101662" + }, + "protein_symbol": { + "label": "Opg134 protein (MPOX)", + "uri": "GENEPIO:0101829" + } }, "gene-NBT03_gp114": { "type": "gene", @@ -3526,7 +6238,23 @@ "gene": "OPG135", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp114", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-118" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-118", + "gene_name": { + "label": "orthopoxvirus gene 135 (MPOX)", + "uri": "GENEPIO:0101320" + }, + "gene_symbol": { + "label": "opg135 gene (MPOX)", + "uri": "GENEPIO:0101495" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp120": { "type": "CDS", @@ -3544,7 +6272,15 @@ "protein_id": "YP_010377117.1", "aa_start": 1, "aa_end": 100, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "IMV membrane protein A9 (MPOX)", + "uri": "GENEPIO:0101663" + }, + "protein_symbol": { + "label": "Opg135 protein (MPOX)", + "uri": "GENEPIO:0101830" + } }, "gene-NBT03_gp115": { "type": "gene", @@ -3557,7 +6293,23 @@ "gene": "OPG136", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp115", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-119" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-119", + "gene_name": { + "label": "orthopoxvirus gene 136 (MPOX)", + "uri": "GENEPIO:0101321" + }, + "gene_symbol": { + "label": "opg136 gene (MPOX)", + "uri": "GENEPIO:0101496" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp121": { "type": "CDS", @@ -3575,7 +6327,15 @@ "protein_id": "YP_010377118.1", "aa_start": 1, "aa_end": 891, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Virion core protein P4a (MPOX)", + "uri": "GENEPIO:0101664" + }, + "protein_symbol": { + "label": "Opg136 protein (MPOX)", + "uri": "GENEPIO:0101831" + } }, "gene-NBT03_gp116": { "type": "gene", @@ -3588,7 +6348,23 @@ "gene": "OPG137", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp116", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-120" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-120", + "gene_name": { + "label": "orthopoxvirus gene 137 (MPOX)", + "uri": "GENEPIO:0101322" + }, + "gene_symbol": { + "label": "opg137 gene (MPOX)", + "uri": "GENEPIO:0101497" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp122": { "type": "CDS", @@ -3606,7 +6382,15 @@ "protein_id": "YP_010377119.1", "aa_start": 1, "aa_end": 318, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "Viral membrane formation protein (MPOX)", + "uri": "GENEPIO:0101665" + }, + "protein_symbol": { + "label": "Opg137 protein (MPOX)", + "uri": "GENEPIO:0101832" + } }, "gene-NBT03_gp117": { "type": "gene", @@ -3619,7 +6403,23 @@ "gene": "OPG138", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp117", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-121" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-121", + "gene_name": { + "label": "orthopoxvirus gene 138 (MPOX)", + "uri": "GENEPIO:0101323" + }, + "gene_symbol": { + "label": "opg138 gene (MPOX)", + "uri": "GENEPIO:0101498" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp123": { "type": "CDS", @@ -3637,7 +6437,15 @@ "protein_id": "YP_010377120.1", "aa_start": 1, "aa_end": 190, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "A12 protein (MPOX)", + "uri": "GENEPIO:0101666" + }, + "protein_symbol": { + "label": "Opg138 protein (MPOX)", + "uri": "GENEPIO:0101833" + } }, "gene-NBT03_gp118": { "type": "gene", @@ -3650,7 +6458,23 @@ "gene": "OPG139", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp118", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-122" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-122", + "gene_name": { + "label": "orthopoxvirus gene 139 (MPOX)", + "uri": "GENEPIO:0101324" + }, + "gene_symbol": { + "label": "opg139 gene (MPOX)", + "uri": "GENEPIO:0101499" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp124": { "type": "CDS", @@ -3668,7 +6492,15 @@ "protein_id": "YP_010377121.1", "aa_start": 1, "aa_end": 70, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "IMV membrane protein A13L (MPOX)", + "uri": "GENEPIO:0101667" + }, + "protein_symbol": { + "label": "Opg139 protein (MPOX)", + "uri": "GENEPIO:0101834" + } }, "gene-NBT03_gp119": { "type": "gene", @@ -3681,7 +6513,23 @@ "gene": "OPG140", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp119", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-123" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-123", + "gene_name": { + "label": "orthopoxvirus gene 140 (MPOX)", + "uri": "GENEPIO:0101325" + }, + "gene_symbol": { + "label": "opg140 gene (MPOX)", + "uri": "GENEPIO:0101500" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp125": { "type": "CDS", @@ -3699,7 +6547,15 @@ "protein_id": "YP_010377122.1", "aa_start": 1, "aa_end": 90, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "IMV membrane protein A14 (MPOX)", + "uri": "GENEPIO:0101668" + }, + "protein_symbol": { + "label": "Opg140 protein (MPOX)", + "uri": "GENEPIO:0101835" + } }, "gene-NBT03_gp120": { "type": "gene", @@ -3712,7 +6568,23 @@ "gene": "OPG141", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp120", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-124" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-124", + "gene_name": { + "label": "orthopoxvirus gene 141 (MPOX)", + "uri": "GENEPIO:0101326" + }, + "gene_symbol": { + "label": "opg141 gene (MPOX)", + "uri": "GENEPIO:0101501" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "A15.5L": { "type": "CDS", @@ -3729,7 +6601,15 @@ "protein_id": "YP_010377123.1", "aa_start": 1, "aa_end": 53, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "DUF1029 domain protein (MPOX)", + "uri": "GENEPIO:0101669" + }, + "protein_symbol": { + "label": "Opg141 protein (MPOX)", + "uri": "GENEPIO:0101836" + } }, "gene-NBT03_gp121": { "type": "gene", @@ -3742,7 +6622,23 @@ "gene": "OPG142", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp121", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-125" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-125", + "gene_name": { + "label": "orthopoxvirus gene 142 (MPOX)", + "uri": "GENEPIO:0101327" + }, + "gene_symbol": { + "label": "opg142 gene (MPOX)", + "uri": "GENEPIO:0101502" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp126": { "type": "CDS", @@ -3760,7 +6656,15 @@ "protein_id": "YP_010377124.1", "aa_start": 1, "aa_end": 94, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Core protein A15 (MPOX)", + "uri": "GENEPIO:0101670" + }, + "protein_symbol": { + "label": "Opg142 protein (MPOX)", + "uri": "GENEPIO:0101837" + } }, "gene-NBT03_gp122": { "type": "gene", @@ -3773,7 +6677,23 @@ "gene": "OPG143", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp122", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-126" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-126", + "gene_name": { + "label": "orthopoxvirus gene 143 (MPOX)", + "uri": "GENEPIO:0101328" + }, + "gene_symbol": { + "label": "opg143 gene (MPOX)", + "uri": "GENEPIO:0101503" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp127": { "type": "CDS", @@ -3791,7 +6711,15 @@ "protein_id": "YP_010377125.1", "aa_start": 1, "aa_end": 377, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "Myristylated protein (MPOX)", + "uri": "GENEPIO:0101624" + }, + "protein_symbol": { + "label": "Opg143 protein (MPOX)", + "uri": "GENEPIO:0101838" + } }, "gene-NBT03_gp123": { "type": "gene", @@ -3804,7 +6732,23 @@ "gene": "OPG144", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp123", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-127" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-127", + "gene_name": { + "label": "orthopoxvirus gene 144 (MPOX)", + "uri": "GENEPIO:0101329" + }, + "gene_symbol": { + "label": "opg144 gene (MPOX)", + "uri": "GENEPIO:0101504" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp128": { "type": "CDS", @@ -3822,7 +6766,15 @@ "protein_id": "YP_010377126.1", "aa_start": 1, "aa_end": 204, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "IMV membrane protein P21 (MPOX)", + "uri": "GENEPIO:0101671" + }, + "protein_symbol": { + "label": "Opg144 protein (MPOX)", + "uri": "GENEPIO:0101839" + } }, "gene-NBT03_gp124": { "type": "gene", @@ -3835,7 +6787,23 @@ "gene": "OPG145", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp124", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-128" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-128", + "gene_name": { + "label": "orthopoxvirus gene 145 (MPOX)", + "uri": "GENEPIO:0101330" + }, + "gene_symbol": { + "label": "opg145 gene (MPOX)", + "uri": "GENEPIO:0101505" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp129": { "type": "CDS", @@ -3853,7 +6821,15 @@ "protein_id": "YP_010377127.1", "aa_start": 1, "aa_end": 492, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "DNA helicase protein (MPOX)", + "uri": "GENEPIO:0101672" + }, + "protein_symbol": { + "label": "Opg145 protein (MPOX)", + "uri": "GENEPIO:0101840" + } }, "gene-NBT03_gp125": { "type": "gene", @@ -3866,7 +6842,23 @@ "gene": "OPG146", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp125", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-129" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-129", + "gene_name": { + "label": "orthopoxvirus gene 146 (MPOX)", + "uri": "GENEPIO:0101331" + }, + "gene_symbol": { + "label": "opg146 gene (MPOX)", + "uri": "GENEPIO:0101506" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp130": { "type": "CDS", @@ -3884,7 +6876,15 @@ "protein_id": "YP_010377128.1", "aa_start": 1, "aa_end": 77, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Zinc finger-like protein (1) (MPOX)", + "uri": "GENEPIO:0101673" + }, + "protein_symbol": { + "label": "Opg146 protein (MPOX)", + "uri": "GENEPIO:0101841" + } }, "gene-NBT03_gp126": { "type": "gene", @@ -3897,7 +6897,23 @@ "gene": "OPG147", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp126", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-130" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-130", + "gene_name": { + "label": "orthopoxvirus gene 147 (MPOX)", + "uri": "GENEPIO:0101332" + }, + "gene_symbol": { + "label": "opg147 gene (MPOX)", + "uri": "GENEPIO:0101507" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp131": { "type": "CDS", @@ -3915,7 +6931,15 @@ "protein_id": "YP_010377129.1", "aa_start": 1, "aa_end": 115, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "IMV membrane protein A21 (MPOX)", + "uri": "GENEPIO:0101674" + }, + "protein_symbol": { + "label": "Opg147 protein (MPOX)", + "uri": "GENEPIO:0101842" + } }, "gene-NBT03_gp127": { "type": "gene", @@ -3928,7 +6952,23 @@ "gene": "OPG148", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp127", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-131" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-131", + "gene_name": { + "label": "orthopoxvirus gene 148 (MPOX)", + "uri": "GENEPIO:0101333" + }, + "gene_symbol": { + "label": "opg148 gene (MPOX)", + "uri": "GENEPIO:0101508" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp132": { "type": "CDS", @@ -3946,7 +6986,15 @@ "protein_id": "YP_010377130.1", "aa_start": 1, "aa_end": 426, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "DNA polymerase processivity factor protein (MPOX)", + "uri": "GENEPIO:0101675" + }, + "protein_symbol": { + "label": "Opg148 protein (MPOX)", + "uri": "GENEPIO:0101843" + } }, "gene-NBT03_gp128": { "type": "gene", @@ -3959,7 +7007,23 @@ "gene": "OPG149", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp128", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-132" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-132", + "gene_name": { + "label": "orthopoxvirus gene 149 (MPOX)", + "uri": "GENEPIO:0101334" + }, + "gene_symbol": { + "label": "opg149 gene (MPOX)", + "uri": "GENEPIO:0101509" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp133": { "type": "CDS", @@ -3977,7 +7041,15 @@ "protein_id": "YP_010377131.1", "aa_start": 1, "aa_end": 187, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "Holliday junction resolvase protein (MPOX)", + "uri": "GENEPIO:0101676" + }, + "protein_symbol": { + "label": "Opg149 protein (MPOX)", + "uri": "GENEPIO:0101844" + } }, "gene-NBT03_gp129": { "type": "gene", @@ -3990,7 +7062,23 @@ "gene": "OPG150", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp129", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-133" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-133", + "gene_name": { + "label": "orthopoxvirus gene 150 (MPOX)", + "uri": "GENEPIO:0101335" + }, + "gene_symbol": { + "label": "opg150 gene (MPOX)", + "uri": "GENEPIO:0101510" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp134": { "type": "CDS", @@ -4008,7 +7096,15 @@ "protein_id": "YP_010377132.1", "aa_start": 1, "aa_end": 382, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "Intermediate transcription factor VITF-3 (2) protein (MPOX)", + "uri": "GENEPIO:0101677" + }, + "protein_symbol": { + "label": "Opg150 protein (MPOX)", + "uri": "GENEPIO:0101845" + } }, "gene-NBT03_gp130": { "type": "gene", @@ -4021,7 +7117,23 @@ "gene": "OPG151", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp130", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-134" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-134", + "gene_name": { + "label": "orthopoxvirus gene 151 (MPOX)", + "uri": "GENEPIO:0101336" + }, + "gene_symbol": { + "label": "opg151 gene (MPOX)", + "uri": "GENEPIO:0101511" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp135": { "type": "CDS", @@ -4039,7 +7151,15 @@ "protein_id": "YP_010377133.1", "aa_start": 1, "aa_end": 1164, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "DNA-dependent RNA polymerase subunit rpo132 protein (MPOX)", + "uri": "GENEPIO:0101678" + }, + "protein_symbol": { + "label": "Opg151 protein (MPOX)", + "uri": "GENEPIO:0101846" + } }, "gene-NBT03_gp131": { "type": "gene", @@ -4052,7 +7172,23 @@ "gene": "OPG153", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp131", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-137" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-137", + "gene_name": { + "label": "orthopoxvirus gene 153 (MPOX)", + "uri": "GENEPIO:0101337" + }, + "gene_symbol": { + "label": "opg153 gene (MPOX)", + "uri": "GENEPIO:0101512" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp138": { "type": "CDS", @@ -4070,7 +7206,15 @@ "protein_id": "YP_010377134.1", "aa_start": 1, "aa_end": 509, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Orthopoxvirus A26L/A30L protein (MPOX)", + "uri": "GENEPIO:0101679" + }, + "protein_symbol": { + "label": "Opg153 protein (MPOX)", + "uri": "GENEPIO:0101847" + } }, "gene-NBT03_gp132": { "type": "gene", @@ -4083,7 +7227,23 @@ "gene": "OPG154", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp132", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-138" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-138", + "gene_name": { + "label": "orthopoxvirus gene 154 (MPOX)", + "uri": "GENEPIO:0101338" + }, + "gene_symbol": { + "label": "opg154 gene (MPOX)", + "uri": "GENEPIO:0101513" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp139": { "type": "CDS", @@ -4101,7 +7261,15 @@ "protein_id": "YP_010377135.1", "aa_start": 1, "aa_end": 110, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "IMV surface fusion protein (MPOX)", + "uri": "GENEPIO:0101680" + }, + "protein_symbol": { + "label": "Opg154 protein (MPOX)", + "uri": "GENEPIO:0101848" + } }, "gene-NBT03_gp133": { "type": "gene", @@ -4114,7 +7282,23 @@ "gene": "OPG155", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp133", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-139" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-139", + "gene_name": { + "label": "orthopoxvirus gene 155 (MPOX)", + "uri": "GENEPIO:0101339" + }, + "gene_symbol": { + "label": "opg155 gene (MPOX)", + "uri": "GENEPIO:0101514" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp140": { "type": "CDS", @@ -4132,7 +7316,15 @@ "protein_id": "YP_010377136.1", "aa_start": 1, "aa_end": 146, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "Envelope protein A28 homolog (MPOX)", + "uri": "GENEPIO:0101681" + }, + "protein_symbol": { + "label": "Opg155 protein (MPOX)", + "uri": "GENEPIO:0101849" + } }, "gene-NBT03_gp134": { "type": "gene", @@ -4145,7 +7337,23 @@ "gene": "OPG156", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp134", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-140" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-140", + "gene_name": { + "label": "orthopoxvirus gene 156 (MPOX)", + "uri": "GENEPIO:0101340" + }, + "gene_symbol": { + "label": "opg156 gene (MPOX)", + "uri": "GENEPIO:0101515" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp141": { "type": "CDS", @@ -4163,7 +7371,15 @@ "protein_id": "YP_010377137.1", "aa_start": 1, "aa_end": 305, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "DNA-directed RNA polymerase 35 kDa subunit protein (MPOX)", + "uri": "GENEPIO:0101682" + }, + "protein_symbol": { + "label": "Opg156 protein (MPOX)", + "uri": "GENEPIO:0101850" + } }, "gene-NBT03_gp135": { "type": "gene", @@ -4176,7 +7392,23 @@ "gene": "OPG157", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp135", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-141" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-141", + "gene_name": { + "label": "orthopoxvirus gene 157 (MPOX)", + "uri": "GENEPIO:0101341" + }, + "gene_symbol": { + "label": "opg157 gene (MPOX)", + "uri": "GENEPIO:0101516" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp142": { "type": "CDS", @@ -4194,7 +7426,15 @@ "protein_id": "YP_010377138.1", "aa_start": 1, "aa_end": 78, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "IMV membrane protein A30 (MPOX)", + "uri": "GENEPIO:0101683" + }, + "protein_symbol": { + "label": "Opg157 protein (MPOX)", + "uri": "GENEPIO:0101851" + } }, "gene-NBT03_gp136": { "type": "gene", @@ -4207,7 +7447,23 @@ "gene": "OPG158", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp136", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-142" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-142", + "gene_name": { + "label": "orthopoxvirus gene 158 (MPOX)", + "uri": "GENEPIO:0101342" + }, + "gene_symbol": { + "label": "opg158 gene (MPOX)", + "uri": "GENEPIO:0101517" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "A32.5L": { "type": "CDS", @@ -4224,7 +7480,15 @@ "protein_id": "YP_010377139.1", "aa_start": 1, "aa_end": 42, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "A32.5L protein (MPOX)", + "uri": "GENEPIO:0101684" + }, + "protein_symbol": { + "label": "Opg158 protein (MPOX)", + "uri": "GENEPIO:0101852" + } }, "gene-NBT03_gp137": { "type": "gene", @@ -4237,7 +7501,23 @@ "gene": "OPG159", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp137", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-143" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-143", + "gene_name": { + "label": "orthopoxvirus gene 159 (MPOX)", + "uri": "GENEPIO:0101343" + }, + "gene_symbol": { + "label": "opg159 gene (MPOX)", + "uri": "GENEPIO:0101518" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp143": { "type": "CDS", @@ -4255,7 +7535,15 @@ "protein_id": "YP_010377140.1", "aa_start": 1, "aa_end": 145, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "CPXV166 protein (MPOX)", + "uri": "GENEPIO:0101685" + }, + "protein_symbol": { + "label": "Opg159 protein (MPOX)", + "uri": "GENEPIO:0101853" + } }, "gene-NBT03_gp138": { "type": "gene", @@ -4268,7 +7556,23 @@ "gene": "OPG160", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp138", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-144" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-144", + "gene_name": { + "label": "orthopoxvirus gene 160 (MPOX)", + "uri": "GENEPIO:0101344" + }, + "gene_symbol": { + "label": "opg160 gene (MPOX)", + "uri": "GENEPIO:0101519" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp144": { "type": "CDS", @@ -4286,7 +7590,15 @@ "protein_id": "YP_010377141.1", "aa_start": 1, "aa_end": 300, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "ATPase A32 protein (MPOX)", + "uri": "GENEPIO:0101686" + }, + "protein_symbol": { + "label": "Opg160 protein (MPOX)", + "uri": "GENEPIO:0101854" + } }, "gene-NBT03_gp139": { "type": "gene", @@ -4299,7 +7611,23 @@ "gene": "OPG161", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp139", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-145" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-145", + "gene_name": { + "label": "orthopoxvirus gene 161 (MPOX)", + "uri": "GENEPIO:0101345" + }, + "gene_symbol": { + "label": "opg161 gene (MPOX)", + "uri": "GENEPIO:0101520" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp145": { "type": "CDS", @@ -4317,7 +7645,15 @@ "protein_id": "YP_010377142.1", "aa_start": 1, "aa_end": 181, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "EEV glycoprotein (1) (MPOX)", + "uri": "GENEPIO:0101687" + }, + "protein_symbol": { + "label": "Opg161 protein (MPOX)", + "uri": "GENEPIO:0101855" + } }, "gene-NBT03_gp140": { "type": "gene", @@ -4330,7 +7666,23 @@ "gene": "OPG162", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp140", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-146" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-146", + "gene_name": { + "label": "orthopoxvirus gene 162 (MPOX)", + "uri": "GENEPIO:0101346" + }, + "gene_symbol": { + "label": "opg162 gene (MPOX)", + "uri": "GENEPIO:0101521" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp146": { "type": "CDS", @@ -4348,7 +7700,15 @@ "protein_id": "YP_010377143.1", "aa_start": 1, "aa_end": 168, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "EEV glycoprotein (2) (MPOX)", + "uri": "GENEPIO:0101688" + }, + "protein_symbol": { + "label": "Opg162 protein (MPOX)", + "uri": "GENEPIO:0101856" + } }, "gene-NBT03_gp141": { "type": "gene", @@ -4361,7 +7721,23 @@ "gene": "OPG163", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp141", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-147" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-147", + "gene_name": { + "label": "orthopoxvirus gene 163 (MPOX)", + "uri": "GENEPIO:0101347" + }, + "gene_symbol": { + "label": "opg163 gene (MPOX)", + "uri": "GENEPIO:0101522" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp147": { "type": "CDS", @@ -4379,7 +7755,15 @@ "protein_id": "YP_010377144.1", "aa_start": 1, "aa_end": 176, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "MHC class II antigen presentation inhibitor protein (MPOX)", + "uri": "GENEPIO:0101689" + }, + "protein_symbol": { + "label": "Opg163 protein (MPOX)", + "uri": "GENEPIO:0101857" + } }, "gene-NBT03_gp142": { "type": "gene", @@ -4392,7 +7776,23 @@ "gene": "OPG164", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp142", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-148" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-148", + "gene_name": { + "label": "orthopoxvirus gene 164 (MPOX)", + "uri": "GENEPIO:0101348" + }, + "gene_symbol": { + "label": "opg164 gene (MPOX)", + "uri": "GENEPIO:0101523" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp148": { "type": "CDS", @@ -4410,7 +7810,15 @@ "protein_id": "YP_010377145.1", "aa_start": 1, "aa_end": 228, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "IEV transmembrane phosphoprotein (MPOX)", + "uri": "GENEPIO:0101690" + }, + "protein_symbol": { + "label": "Opg164 protein (MPOX)", + "uri": "GENEPIO:0101858" + } }, "gene-NBT03_gp143": { "type": "gene", @@ -4423,7 +7831,23 @@ "gene": "OPG165", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp143", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-149" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-149", + "gene_name": { + "label": "orthopoxvirus gene 165 (MPOX)", + "uri": "GENEPIO:0101349" + }, + "gene_symbol": { + "label": "opg165 gene (MPOX)", + "uri": "GENEPIO:0101524" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp149": { "type": "CDS", @@ -4441,7 +7865,15 @@ "protein_id": "YP_010377146.1", "aa_start": 1, "aa_end": 268, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "CPXV173 protein (MPOX)", + "uri": "GENEPIO:0101691" + }, + "protein_symbol": { + "label": "Opg165 protein (MPOX)", + "uri": "GENEPIO:0101859" + } }, "gene-NBT03_gp144": { "type": "gene", @@ -4454,7 +7886,23 @@ "gene": "OPG167", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp144", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-150" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-150", + "gene_name": { + "label": "orthopoxvirus gene 166 (MPOX)", + "uri": "GENEPIO:0101350" + }, + "gene_symbol": { + "label": "opg166 gene (MPOX)", + "uri": "GENEPIO:0101525" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp150": { "type": "CDS", @@ -4472,7 +7920,15 @@ "protein_id": "YP_010377147.1", "aa_start": 1, "aa_end": 277, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "CD47-like protein (MPOX)", + "uri": "GENEPIO:0101693" + }, + "protein_symbol": { + "label": "Opg167 protein (MPOX)", + "uri": "GENEPIO:0101861" + } }, "gene-NBT03_gp145": { "type": "gene", @@ -4485,7 +7941,23 @@ "gene": "OPG170", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp145", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-151" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-151", + "gene_name": { + "label": "orthopoxvirus gene 167 (MPOX)", + "uri": "GENEPIO:0101351" + }, + "gene_symbol": { + "label": "opg167 gene (MPOX)", + "uri": "GENEPIO:0101526" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp151": { "type": "CDS", @@ -4503,7 +7975,15 @@ "protein_id": "YP_010377148.1", "aa_start": 1, "aa_end": 221, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Chemokine binding protein (MPOX)", + "uri": "GENEPIO:0101557" + }, + "protein_symbol": { + "label": "Opg170 protein (MPOX)", + "uri": "GENEPIO:0101862" + } }, "gene-NBT03_gp146": { "type": "gene", @@ -4516,7 +7996,23 @@ "gene": "OPG171", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp146", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-152" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-152", + "gene_name": { + "label": "orthopoxvirus gene 170 (MPOX)", + "uri": "GENEPIO:0101352" + }, + "gene_symbol": { + "label": "opg170 gene (MPOX)", + "uri": "GENEPIO:0101527" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp152": { "type": "CDS", @@ -4534,7 +8030,15 @@ "protein_id": "YP_010377149.1", "aa_start": 1, "aa_end": 133, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "Profilin domain protein (MPOX)", + "uri": "GENEPIO:0101694" + }, + "protein_symbol": { + "label": "Opg171 protein (MPOX)", + "uri": "GENEPIO:0101863" + } }, "gene-NBT03_gp147": { "type": "gene", @@ -4547,7 +8051,23 @@ "gene": "OPG172", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp147", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-153" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-153", + "gene_name": { + "label": "orthopoxvirus gene 171 (MPOX)", + "uri": "GENEPIO:0101353" + }, + "gene_symbol": { + "label": "opg171 gene (MPOX)", + "uri": "GENEPIO:0101528" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp153": { "type": "CDS", @@ -4565,7 +8085,15 @@ "protein_id": "YP_010377150.1", "aa_start": 1, "aa_end": 196, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "Type-I membrane glycoprotein (MPOX)", + "uri": "GENEPIO:0101695" + }, + "protein_symbol": { + "label": "Opg172 protein (MPOX)", + "uri": "GENEPIO:0101864" + } }, "gene-NBT03_gp148": { "type": "gene", @@ -4578,7 +8106,23 @@ "gene": "OPG173", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp148", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-154" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-154", + "gene_name": { + "label": "orthopoxvirus gene 172 (MPOX)", + "uri": "GENEPIO:0101354" + }, + "gene_symbol": { + "label": "opg172 gene (MPOX)", + "uri": "GENEPIO:0101529" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp154": { "type": "CDS", @@ -4596,7 +8140,15 @@ "protein_id": "YP_010377151.1", "aa_start": 1, "aa_end": 74, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "MPXVgp154 protein (MPOX)", + "uri": "GENEPIO:0101696" + }, + "protein_symbol": { + "label": "Opg173 protein (MPOX)", + "uri": "GENEPIO:0101865" + } }, "gene-NBT03_gp149": { "type": "gene", @@ -4609,7 +8161,23 @@ "gene": "OPG174", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp149", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-155" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-155", + "gene_name": { + "label": "orthopoxvirus gene 173 (MPOX)", + "uri": "GENEPIO:0101355" + }, + "gene_symbol": { + "label": "opg173 gene (MPOX)", + "uri": "GENEPIO:0101530" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp158": { "type": "CDS", @@ -4627,7 +8195,15 @@ "protein_id": "YP_010377152.1", "aa_start": 1, "aa_end": 346, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "Hydroxysteroid dehydrogenase protein (MPOX)", + "uri": "GENEPIO:0101697" + }, + "protein_symbol": { + "label": "Opg174 protein (MPOX)", + "uri": "GENEPIO:0101866" + } }, "gene-NBT03_gp150": { "type": "gene", @@ -4640,7 +8216,23 @@ "gene": "OPG175", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp150", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-156" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-156", + "gene_name": { + "label": "orthopoxvirus gene 174 (MPOX)", + "uri": "GENEPIO:0101356" + }, + "gene_symbol": { + "label": "opg174 gene (MPOX)", + "uri": "GENEPIO:0101531" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp156": { "type": "CDS", @@ -4658,7 +8250,15 @@ "protein_id": "YP_010377153.1", "aa_start": 1, "aa_end": 125, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "Copper/zinc superoxide dismutase protein (MPOX)", + "uri": "GENEPIO:0101698" + }, + "protein_symbol": { + "label": "Opg175 protein (MPOX)", + "uri": "GENEPIO:0101867" + } }, "gene-NBT03_gp151": { "type": "gene", @@ -4671,7 +8271,23 @@ "gene": "OPG176", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp151", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-157" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-157", + "gene_name": { + "label": "orthopoxvirus gene 175 (MPOX)", + "uri": "GENEPIO:0101357" + }, + "gene_symbol": { + "label": "opg175 gene (MPOX)", + "uri": "GENEPIO:0101532" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp157": { "type": "CDS", @@ -4689,7 +8305,15 @@ "protein_id": "YP_010377154.1", "aa_start": 1, "aa_end": 240, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Bcl-2-like protein (MPOX)", + "uri": "GENEPIO:0101568" + }, + "protein_symbol": { + "label": "Opg176 protein (MPOX)", + "uri": "GENEPIO:0101868" + } }, "gene-NBT03_gp152": { "type": "gene", @@ -4702,7 +8326,23 @@ "gene": "OPG178", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp152", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-158" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-158", + "gene_name": { + "label": "orthopoxvirus gene 176 (MPOX)", + "uri": "GENEPIO:0101358" + }, + "gene_symbol": { + "label": "opg176 gene (MPOX)", + "uri": "GENEPIO:0101533" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp159": { "type": "CDS", @@ -4720,7 +8360,15 @@ "protein_id": "YP_010377155.1", "aa_start": 1, "aa_end": 204, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "Thymidylate kinase protein (MPOX)", + "uri": "GENEPIO:0101699" + }, + "protein_symbol": { + "label": "Opg178 protein (MPOX)", + "uri": "GENEPIO:0101869" + } }, "gene-NBT03_gp153": { "type": "gene", @@ -4733,7 +8381,23 @@ "gene": "OPG180", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp153", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-159" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-159", + "gene_name": { + "label": "orthopoxvirus gene 178 (MPOX)", + "uri": "GENEPIO:0101359" + }, + "gene_symbol": { + "label": "opg178 gene (MPOX)", + "uri": "GENEPIO:0101534" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp160": { "type": "CDS", @@ -4751,7 +8415,15 @@ "protein_id": "YP_010377156.1", "aa_start": 1, "aa_end": 559, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "DNA ligase (2) protein (MPOX)", + "uri": "GENEPIO:0101700" + }, + "protein_symbol": { + "label": "Opg180 protein (MPOX)", + "uri": "GENEPIO:0101870" + } }, "gene-NBT03_gp154": { "type": "gene", @@ -4764,7 +8436,23 @@ "gene": "OPG181", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp154", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-160" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-160", + "gene_name": { + "label": "orthopoxvirus gene 180 (MPOX)", + "uri": "GENEPIO:0101360" + }, + "gene_symbol": { + "label": "opg180 gene (MPOX)", + "uri": "GENEPIO:0101535" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp161": { "type": "CDS", @@ -4782,7 +8470,15 @@ "protein_id": "YP_010377157.1", "aa_start": 1, "aa_end": 334, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "M137R protein (MPOX)", + "uri": "GENEPIO:0101701" + }, + "protein_symbol": { + "label": "Opg181 protein (MPOX)", + "uri": "GENEPIO:0101871" + } }, "gene-NBT03_gp155": { "type": "gene", @@ -4795,7 +8491,23 @@ "gene": "OPG185", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp155", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-162" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-162", + "gene_name": { + "label": "orthopoxvirus gene 181 (MPOX)", + "uri": "GENEPIO:0101361" + }, + "gene_symbol": { + "label": "opg181 gene (MPOX)", + "uri": "GENEPIO:0101536" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp163": { "type": "CDS", @@ -4813,7 +8525,15 @@ "protein_id": "YP_010377158.1", "aa_start": 1, "aa_end": 313, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Hemagglutinin protein (MPOX)", + "uri": "GENEPIO:0101702" + }, + "protein_symbol": { + "label": "Opg185 protein (MPOX)", + "uri": "GENEPIO:0101872" + } }, "gene-NBT03_gp156": { "type": "gene", @@ -4826,7 +8546,23 @@ "gene": "OPG187", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp156", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-163" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-163", + "gene_name": { + "label": "orthopoxvirus gene 185 (MPOX)", + "uri": "GENEPIO:0101362" + }, + "gene_symbol": { + "label": "opg185 gene (MPOX)", + "uri": "GENEPIO:0101537" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp164": { "type": "CDS", @@ -4844,7 +8580,15 @@ "protein_id": "YP_010377159.1", "aa_start": 1, "aa_end": 303, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "Ser/thr kinase protein (MPOX)", + "uri": "GENEPIO:0101703" + }, + "protein_symbol": { + "label": "Opg187 protein (MPOX)", + "uri": "GENEPIO:0101873" + } }, "gene-NBT03_gp157": { "type": "gene", @@ -4857,7 +8601,23 @@ "gene": "OPG188", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp157", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-164" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-164", + "gene_name": { + "label": "orthopoxvirus gene 187 (MPOX)", + "uri": "GENEPIO:0101363" + }, + "gene_symbol": { + "label": "opg187 gene (MPOX)", + "uri": "GENEPIO:0101538" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp165": { "type": "CDS", @@ -4875,7 +8635,15 @@ "protein_id": "YP_010377160.1", "aa_start": 1, "aa_end": 503, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "Schlafen (1) protein (MPOX)", + "uri": "GENEPIO:0101704" + }, + "protein_symbol": { + "label": "Opg188 protein (MPOX)", + "uri": "GENEPIO:0101874" + } }, "gene-NBT03_gp158": { "type": "gene", @@ -4888,7 +8656,23 @@ "gene": "OPG189", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp158", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-165" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-165", + "gene_name": { + "label": "orthopoxvirus gene 188 (MPOX)", + "uri": "GENEPIO:0101364" + }, + "gene_symbol": { + "label": "opg188 gene (MPOX)", + "uri": "GENEPIO:0101539" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp166": { "type": "CDS", @@ -4906,7 +8690,15 @@ "protein_id": "YP_010377161.1", "aa_start": 1, "aa_end": 561, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "Ankyrin repeat protein (25) (MPOX)", + "uri": "GENEPIO:0101559" + }, + "protein_symbol": { + "label": "Opg189 protein (MPOX)", + "uri": "GENEPIO:0101875" + } }, "gene-NBT03_gp159": { "type": "gene", @@ -4919,7 +8711,23 @@ "gene": "OPG190", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp159", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-166" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-166", + "gene_name": { + "label": "orthopoxvirus gene 189 (MPOX)", + "uri": "GENEPIO:0101365" + }, + "gene_symbol": { + "label": "opg189 gene (MPOX)", + "uri": "GENEPIO:0101540" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp167": { "type": "CDS", @@ -4937,7 +8745,15 @@ "protein_id": "YP_010377162.1", "aa_start": 1, "aa_end": 317, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "EEV type-I membrane glycoprotein (MPOX)", + "uri": "GENEPIO:0101705" + }, + "protein_symbol": { + "label": "Opg190 protein (MPOX)", + "uri": "GENEPIO:0101876" + } }, "gene-NBT03_gp160": { "type": "gene", @@ -4950,7 +8766,23 @@ "gene": "OPG191", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp160", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-167" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-167", + "gene_name": { + "label": "orthopoxvirus gene 190 (MPOX)", + "uri": "GENEPIO:0101366" + }, + "gene_symbol": { + "label": "opg190 gene (MPOX)", + "uri": "GENEPIO:0101541" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp168": { "type": "CDS", @@ -4968,7 +8800,15 @@ "protein_id": "YP_010377163.1", "aa_start": 1, "aa_end": 168, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "Ankyrin-like protein (46) (MPOX)", + "uri": "GENEPIO:0101706" + }, + "protein_symbol": { + "label": "Opg191 protein (MPOX)", + "uri": "GENEPIO:0101877" + } }, "gene-NBT03_gp161": { "type": "gene", @@ -4981,7 +8821,23 @@ "gene": "OPG192", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp161", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-168" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-168", + "gene_name": { + "label": "orthopoxvirus gene 191 (MPOX)", + "uri": "GENEPIO:0101367" + }, + "gene_symbol": { + "label": "opg191 gene (MPOX)", + "uri": "GENEPIO:0101542" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp169": { "type": "CDS", @@ -4999,7 +8855,15 @@ "protein_id": "YP_010377164.1", "aa_start": 1, "aa_end": 182, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Virulence protein (MPOX)", + "uri": "GENEPIO:0101707" + }, + "protein_symbol": { + "label": "Opg192 protein (MPOX)", + "uri": "GENEPIO:0101878" + } }, "gene-NBT03_gp162": { "type": "gene", @@ -5012,7 +8876,23 @@ "gene": "OPG193", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp162", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-169" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-169", + "gene_name": { + "label": "orthopoxvirus gene 192 (MPOX)", + "uri": "GENEPIO:0101368" + }, + "gene_symbol": { + "label": "opg192 gene (MPOX)", + "uri": "GENEPIO:0101543" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp170": { "type": "CDS", @@ -5030,7 +8910,15 @@ "protein_id": "YP_010377165.1", "aa_start": 1, "aa_end": 267, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "Soluble interferon-gamma receptor-like protein (MPOX)", + "uri": "GENEPIO:0101708" + }, + "protein_symbol": { + "label": "Opg193 protein (MPOX)", + "uri": "GENEPIO:0101879" + } }, "gene-NBT03_gp163": { "type": "gene", @@ -5043,7 +8931,23 @@ "gene": "OPG195", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp163", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-170" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-170", + "gene_name": { + "label": "orthopoxvirus gene 193 (MPOX)", + "uri": "GENEPIO:0101369" + }, + "gene_symbol": { + "label": "opg193 gene (MPOX)", + "uri": "GENEPIO:0101544" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp171": { "type": "CDS", @@ -5061,7 +8965,15 @@ "protein_id": "YP_010377166.1", "aa_start": 1, "aa_end": 221, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "Intracellular viral protein (MPOX)", + "uri": "GENEPIO:0101709" + }, + "protein_symbol": { + "label": "Opg195 protein (MPOX)", + "uri": "GENEPIO:0101880" + } }, "gene-NBT03_gp164": { "type": "gene", @@ -5074,7 +8986,23 @@ "gene": "OPG197", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp164", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-171" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-171", + "gene_name": { + "label": "orthopoxvirus gene 195 (MPOX)", + "uri": "GENEPIO:0101370" + }, + "gene_symbol": { + "label": "opg195 gene (MPOX)", + "uri": "GENEPIO:0101545" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "Hypothetical protein (Cop-B11R)": { "type": "CDS", @@ -5091,7 +9019,15 @@ "protein_id": "YP_010377167.1", "aa_start": 1, "aa_end": 100, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "CPXV205 protein (MPOX)", + "uri": "GENEPIO:0101710" + }, + "protein_symbol": { + "label": "Opg197 protein (MPOX)", + "uri": "GENEPIO:0101881" + } }, "gene-NBT03_gp165": { "type": "gene", @@ -5104,7 +9040,23 @@ "gene": "OPG198", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp165", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-172" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-172", + "gene_name": { + "label": "orthopoxvirus gene 197 (MPOX)", + "uri": "GENEPIO:0101371" + }, + "gene_symbol": { + "label": "opg197 gene (MPOX)", + "uri": "GENEPIO:0101546" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp172": { "type": "CDS", @@ -5122,7 +9074,15 @@ "protein_id": "YP_010377168.1", "aa_start": 1, "aa_end": 282, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Ser/thr kinase protein (MPOX)", + "uri": "GENEPIO:0101703" + }, + "protein_symbol": { + "label": "Opg198 protein (MPOX)", + "uri": "GENEPIO:0101882" + } }, "gene-NBT03_gp166": { "type": "gene", @@ -5135,7 +9095,23 @@ "gene": "OPG199", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp166", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-173" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-173", + "gene_name": { + "label": "orthopoxvirus gene 198 (MPOX)", + "uri": "GENEPIO:0101372" + }, + "gene_symbol": { + "label": "opg198 gene (MPOX)", + "uri": "GENEPIO:0101547" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp173": { "type": "CDS", @@ -5153,7 +9129,15 @@ "protein_id": "YP_010377169.1", "aa_start": 1, "aa_end": 344, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "Serpin protein (MPOX)", + "uri": "GENEPIO:0101574" + }, + "protein_symbol": { + "label": "Opg199 protein (MPOX)", + "uri": "GENEPIO:0101883" + } }, "gene-NBT03_gp167": { "type": "gene", @@ -5166,7 +9150,23 @@ "gene": "OPG200", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp167", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-174" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-174", + "gene_name": { + "label": "orthopoxvirus gene 199 (MPOX)", + "uri": "GENEPIO:0101373" + }, + "gene_symbol": { + "label": "opg199 gene (MPOX)", + "uri": "GENEPIO:0101548" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp174": { "type": "CDS", @@ -5184,7 +9184,15 @@ "protein_id": "YP_010377170.1", "aa_start": 1, "aa_end": 149, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "Bcl-2-like protein (MPOX)", + "uri": "GENEPIO:0101568" + }, + "protein_symbol": { + "label": "Opg200 protein (MPOX)", + "uri": "GENEPIO:0101884" + } }, "gene-NBT03_gp168": { "type": "gene", @@ -5197,7 +9205,23 @@ "gene": "OPG204", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp168", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-177" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-177", + "gene_name": { + "label": "orthopoxvirus gene 200 (MPOX)", + "uri": "GENEPIO:0101374" + }, + "gene_symbol": { + "label": "opg200 gene (MPOX)", + "uri": "GENEPIO:0101549" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp177": { "type": "CDS", @@ -5215,7 +9239,15 @@ "protein_id": "YP_010377172.1", "aa_start": 1, "aa_end": 351, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "IFN-alpha/beta-receptor-like secreted glycoprotein (MPOX)", + "uri": "GENEPIO:0101711" + }, + "protein_symbol": { + "label": "Opg204 protein (MPOX)", + "uri": "GENEPIO:0101885" + } }, "gene-NBT03_gp169": { "type": "gene", @@ -5228,7 +9260,23 @@ "gene": "OPG205", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp169", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-178" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-178", + "gene_name": { + "label": "orthopoxvirus gene 204 (MPOX)", + "uri": "GENEPIO:0101375" + }, + "gene_symbol": { + "label": "opg204 gene (MPOX)", + "uri": "GENEPIO:0101550" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp178": { "type": "CDS", @@ -5246,7 +9294,15 @@ "protein_id": "YP_010377173.1", "aa_start": 1, "aa_end": 787, - "color": "rgb(117, 182, 129)" + "color": "rgb(117, 182, 129)", + "protein_name": { + "label": "Ankyrin repeat protein (44) (MPOX)", + "uri": "GENEPIO:0101712" + }, + "protein_symbol": { + "label": "Opg205 protein (MPOX)", + "uri": "GENEPIO:0101886" + } }, "gene-NBT03_gp170": { "type": "gene", @@ -5259,7 +9315,23 @@ "gene": "OPG208", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp170", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-180" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-180", + "gene_name": { + "label": "orthopoxvirus gene 205 (MPOX)", + "uri": "GENEPIO:0101376" + }, + "gene_symbol": { + "label": "opg205 gene (MPOX)", + "uri": "GENEPIO:0101551" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp180": { "type": "CDS", @@ -5277,7 +9349,15 @@ "protein_id": "YP_010377174.1", "aa_start": 1, "aa_end": 357, - "color": "rgb(96, 170, 158)" + "color": "rgb(96, 170, 158)", + "protein_name": { + "label": "Serpin protein (MPOX)", + "uri": "GENEPIO:0101574" + }, + "protein_symbol": { + "label": "Opg208 protein (MPOX)", + "uri": "GENEPIO:0101887" + } }, "gene-NBT03_gp171": { "type": "gene", @@ -5290,7 +9370,23 @@ "gene": "OPG209", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp171", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-181" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-181", + "gene_name": { + "label": "orthopoxvirus gene 208 (MPOX)", + "uri": "GENEPIO:0101377" + }, + "gene_symbol": { + "label": "opg208 gene (MPOX)", + "uri": "GENEPIO:0101552" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp181": { "type": "CDS", @@ -5308,7 +9404,15 @@ "protein_id": "YP_010377175.1", "aa_start": 1, "aa_end": 190, - "color": "rgb(217, 173, 61)" + "color": "rgb(217, 173, 61)", + "protein_name": { + "label": "Virulence protein (MPOX)", + "uri": "GENEPIO:0101707" + }, + "protein_symbol": { + "label": "Opg209 protein (MPOX)", + "uri": "GENEPIO:0101888" + } }, "gene-NBT03_gp172": { "type": "gene", @@ -5321,7 +9425,23 @@ "gene": "OPG210", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp172", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-182" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-182", + "gene_name": { + "label": "orthopoxvirus gene 209 (MPOX)", + "uri": "GENEPIO:0101378" + }, + "gene_symbol": { + "label": "opg209 gene (MPOX)", + "uri": "GENEPIO:0101553" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp182": { "type": "CDS", @@ -5339,7 +9459,15 @@ "protein_id": "YP_010377176.1", "aa_start": 1, "aa_end": 1880, - "color": "rgb(80, 151, 186)" + "color": "rgb(80, 151, 186)", + "protein_name": { + "label": "B22R family protein (MPOX)", + "uri": "GENEPIO:0101713" + }, + "protein_symbol": { + "label": "Opg210 protein (MPOX)", + "uri": "GENEPIO:0101889" + } }, "gene-NBT03_gp173": { "type": "gene", @@ -5352,7 +9480,23 @@ "gene": "OPG005", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp173", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-184" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-184", + "gene_name": { + "label": "orthopoxvirus gene 210 (MPOX)", + "uri": "GENEPIO:0101379" + }, + "gene_symbol": { + "label": "opg210 gene (MPOX)", + "uri": "GENEPIO:0101554" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp185": { "type": "CDS", @@ -5370,7 +9514,15 @@ "protein_id": "YP_010377177.1", "aa_start": 1, "aa_end": 153, - "color": "rgb(230, 112, 48)" + "color": "rgb(230, 112, 48)", + "protein_name": { + "label": "Bcl-2-like protein (MPOX)", + "uri": "GENEPIO:0101568" + }, + "protein_symbol": { + "label": "Opg005 protein (MPOX)", + "uri": "GENEPIO:0101890" + } }, "gene-NBT03_gp174": { "type": "gene", @@ -5382,7 +9534,23 @@ "gbkey": "Gene", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp174", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-186" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-186", + "gene_name": { + "label": "orthopoxvirus gene 005 (MPOX)", + "uri": "GENEPIO:0101380" + }, + "gene_symbol": { + "label": "opg005 gene (MPOX)", + "uri": "GENEPIO:0101555" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "hypothetical protein": { "type": "CDS", @@ -5398,7 +9566,15 @@ "protein_id": "YP_010377184.1", "aa_start": 1, "aa_end": 176, - "color": "rgb(142, 188, 102)" + "color": "rgb(142, 188, 102)", + "protein_name": { + "label": "Brix domain protein (MPOX)", + "uri": "GENEPIO:0101714" + }, + "protein_symbol": { + "label": "Opg016 protein (MPOX)", + "uri": "GENEPIO:0101891" + } }, "gene-NBT03_gp175": { "type": "gene", @@ -5410,7 +9586,23 @@ "gbkey": "Gene", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp175", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-187" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-187", + "gene_name": { + "label": "orthopoxvirus gene 016 (MPOX)", + "uri": "GENEPIO:0101381" + }, + "gene_symbol": { + "label": "opg016 gene (MPOX)", + "uri": "GENEPIO:0101556" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" + } }, "MPXVgp188": { "type": "CDS", @@ -5427,7 +9619,15 @@ "protein_id": "YP_010377179.1", "aa_start": 1, "aa_end": 437, - "color": "rgb(229, 150, 55)" + "color": "rgb(229, 150, 55)", + "protein_name": { + "label": "Ankyrin repeat protein (39) (MPOX)", + "uri": "GENEPIO:0101560" + }, + "protein_symbol": { + "label": "Opg015 protein (MPOX)", + "uri": "GENEPIO:0101723" + } }, "gene-NBT03_gp176": { "type": "gene", @@ -5440,7 +9640,23 @@ "gene": "OPG003", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp176", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-188" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-188", + "gene_name": { + "label": "orthopoxvirus gene 015 (MPOX)", + "uri": "GENEPIO:0101210" + }, + "gene_symbol": { + "label": "opg015 gene (MPOX)", + "uri": "GENEPIO:0101385" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "reverse gene orientation", + "uri": "GENEPIO:0700005" + } }, "MPXVgp189": { "type": "CDS", @@ -5458,7 +9674,15 @@ "protein_id": "YP_010377180.1", "aa_start": 1, "aa_end": 588, - "color": "rgb(170, 189, 82)" + "color": "rgb(170, 189, 82)", + "protein_name": { + "label": "Ankyrin repeat protein (25) (MPOX)", + "uri": "GENEPIO:0101559" + }, + "protein_symbol": { + "label": "Opg003 protein (MPOX)", + "uri": "GENEPIO:0101722" + } }, "gene-NBT03_gp177": { "type": "gene", @@ -5471,7 +9695,23 @@ "gene": "OPG002", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp177", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-189" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-189", + "gene_name": { + "label": "orthopoxvirus gene 003 (MPOX)", + "uri": "GENEPIO:0101209" + }, + "gene_symbol": { + "label": "opg003 gene (MPOX)", + "uri": "GENEPIO:0101384" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "reverse gene orientation", + "uri": "GENEPIO:0700005" + } }, "MPXVgp190": { "type": "CDS", @@ -5489,7 +9729,15 @@ "protein_id": "YP_010377181.1", "aa_start": 1, "aa_end": 349, - "color": "rgb(223, 67, 39)" + "color": "rgb(223, 67, 39)", + "protein_name": { + "label": "Crm-B secreted TNF-alpha-receptor-like protein (MPOX)", + "uri": "GENEPIO:0101558" + }, + "protein_symbol": { + "label": "Opg002 protein (MPOX)", + "uri": "GENEPIO:0101721" + } }, "gene-NBT03_gp178": { "type": "gene", @@ -5502,7 +9750,23 @@ "gene": "OPG001", "gene_biotype": "protein_coding", "locus_tag": "NBT03_gp178", - "old_locus_tag": "MPXV-M5312_HM12_Rivers-190" + "old_locus_tag": "MPXV-M5312_HM12_Rivers-190", + "gene_name": { + "label": "orthopoxvirus gene 002 (MPOX)", + "uri": "GENEPIO:0101208" + }, + "gene_symbol": { + "label": "opg002 gene (MPOX)", + "uri": "GENEPIO:0101383" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "reverse gene orientation", + "uri": "GENEPIO:0700005" + } }, "MPXVgp191": { "type": "CDS", @@ -5520,7 +9784,15 @@ "protein_id": "YP_010377182.1", "aa_start": 1, "aa_end": 246, - "color": "rgb(196, 185, 69)" + "color": "rgb(196, 185, 69)", + "protein_name": { + "label": "Chemokine binding protein (MPOX)", + "uri": "GENEPIO:0101557" + }, + "protein_symbol": { + "label": "Opg001 protein (MPOX)", + "uri": "GENEPIO:0101720" + } }, "INTERGENIC": { "type": "INTERGENIC", diff --git a/bin/addontologyterms2json.py b/bin/addontologyterms2json.py index 06f3ec00..c589a540 100644 --- a/bin/addontologyterms2json.py +++ b/bin/addontologyterms2json.py @@ -60,8 +60,12 @@ def parse_args(): if ONTOLOGY_GENES_DICT[gene_entry]["Dbxref"] == gene_ids: gene_name = ONTOLOGY_GENES_DICT[gene_entry]["gene_name"] gene_symbol = ONTOLOGY_GENES_DICT[gene_entry]["gene_symbol"] + strand_orientation = ONTOLOGY_GENES_DICT[gene_entry]["strand_orientation"] + gene_orientation = ONTOLOGY_GENES_DICT[gene_entry]["gene_orientation"] GENE_PROTEIN_POSITIONS_DICT[entry]["gene_name"] = gene_name GENE_PROTEIN_POSITIONS_DICT[entry]["gene_symbol"] = gene_symbol + GENE_PROTEIN_POSITIONS_DICT[entry]["strand_orientation"] = strand_orientation + GENE_PROTEIN_POSITIONS_DICT[entry]["gene_orientation"] = gene_orientation # Convert the dictionary of features to a JSON string From 9a53e60fc176e5764d81d59b95d7f0d023fd9652 Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 30 Sep 2024 22:33:58 -0700 Subject: [PATCH 045/161] make code useful for SC2 or MPOX --- bin/robot2json.py | 26 +++++++++++++++++++------- 1 file changed, 19 insertions(+), 7 deletions(-) diff --git a/bin/robot2json.py b/bin/robot2json.py index a1518ddd..d44824c9 100644 --- a/bin/robot2json.py +++ b/bin/robot2json.py @@ -46,7 +46,6 @@ def parse_args(): gene_symbols['gene_symbol_id'] = gene_symbols['Ontology ID'] gene_symbols = gene_symbols[['Dbxref', 'gene_symbol', 'gene_symbol_id']] gene_symbols['Dbxref'] = gene_symbols['Dbxref'].str.replace("GeneID", "NCBIGene") #'JSON_match' - gene_symbols.to_csv("GENE_SYMBOLS_HAVOC.tsv", sep='\t', header=True, index=False) genes = pd.merge(gene_names, gene_symbols, on='Dbxref', how='left') @@ -57,13 +56,11 @@ def parse_args(): # add gene orientation genes['gene_orientation'] = "forward gene orientation" genes['gene_orientation_id'] = "GENEPIO:0700004" - reverse_gene_ids = ["NCBIGene:72551595", "NCBIGene:72551594", "NCBIGene:72551593", "NCBIGene:72551592"] + reverse_gene_ids = ["NCBIGene:72551595", "NCBIGene:72551594", "NCBIGene:72551593", "NCBIGene:72551592"] # for MPOX #print(genes[genes['gene_symbol'].duplicated(keep=False)]) #show which genes are duplicated genes.loc[genes["Dbxref"].isin(reverse_gene_ids), 'gene_orientation'] = "reverse gene orientation" genes.loc[genes["Dbxref"].isin(reverse_gene_ids), 'gene_orientation_id'] = "GENEPIO:0700005" - genes.to_csv("GENES_HAVOC.tsv", sep='\t', header=True, index=False) - # Define a custom function to create a nested structure # ncbigene and the gene name are all the same, this is causing HAVOC def custom_nested_structure_genes(row): @@ -94,15 +91,30 @@ def custom_nested_structure_genes(row): protein_names = sars[sars['parent class'].str.contains("protein name")].copy(deep=True) protein_names['protein_name'] = protein_names['label'] protein_names['protein_name_id'] = protein_names['Ontology ID'] - protein_names['protein_id'] = protein_names['Dbxref'].str.split(pat=",", expand=True)[0].str.split(":", expand=True)[1] # extract eg. "YP_010377182.1" from "GenBank:YP_010377182.1,GeneID:72551595" + if protein_names['Dbxref'].str.contains(",GeneID", regex=False).any(): + protein_names['protein_id'] = protein_names['Dbxref'].str.split(pat=",GeneID", expand=True)[0] + else: + protein_names['protein_id'] = protein_names['Dbxref'] + if protein_names['protein_id'].str.contains("GenBank:", regex=False).any(): + protein_names['protein_id'] = protein_names['protein_id'].str.split("GenBank:", expand=True)[1] # extract eg. "YP_010377182.1" from "GenBank:YP_010377182.1,GeneID:72551595" + else: + protein_names['protein_id'] = protein_names['protein_id'] + #print(protein_names['protein_id']) protein_names = protein_names[['protein_id', 'protein_name', 'protein_name_id']] protein_symbols = sars[sars['parent class'].str.contains("protein symbol")].copy(deep=True) protein_symbols['protein_symbol'] = protein_symbols['label'] protein_symbols['protein_symbol_id'] = protein_symbols['Ontology ID'] - protein_symbols['protein_id'] = protein_symbols['Dbxref'].str.split(pat=",", expand=True)[0].str.split(":", expand=True)[1] # extract eg. "YP_010377182.1" from "GenBank:YP_010377182.1,GeneID:72551595" + if protein_symbols['Dbxref'].str.contains(",GeneID", regex=False).any(): + protein_symbols['protein_id'] = protein_symbols['Dbxref'].str.split(pat=",GeneID", expand=True)[0] + else: + protein_symbols['protein_id'] = protein_symbols['Dbxref'] + if protein_symbols['protein_id'].str.contains("GenBank:", regex=False).any(): + protein_symbols['protein_id'] = protein_symbols['protein_id'].str.split("GenBank:", expand=True)[1] # extract eg. "YP_010377182.1" from "GenBank:YP_010377182.1,GeneID:72551595" + else: + protein_symbols['protein_id'] = protein_symbols['protein_id'] # extract eg. "YP_010377182.1" from "GenBank:YP_010377182.1,GeneID:72551595" protein_symbols = protein_symbols[['protein_id', 'protein_symbol', 'protein_symbol_id']] - + #print(protein_symbols['protein_id']) proteins = pd.merge(protein_names, protein_symbols, on='protein_id', how='left') # Define a custom function to create a nested structure From 2c62b20fa65d4ab1f1a5498a9d8860a22d423e14 Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 30 Sep 2024 22:35:32 -0700 Subject: [PATCH 046/161] Update SARS-CoV-2 JSONs with gene and strand orientations: --- .../NC_045512.2/NC_045512.2_ROBOT.tsv | 47 ++++++++++ .../NC_045512.2_ontology_genes.json | 88 +++++++++++++++++++ 2 files changed, 135 insertions(+) create mode 100644 assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ROBOT.tsv diff --git a/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ROBOT.tsv b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ROBOT.tsv new file mode 100644 index 00000000..bf617a85 --- /dev/null +++ b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ROBOT.tsv @@ -0,0 +1,47 @@ +Issues / Notes Dbxref Ontology ID parent class Equivalence axiom Subclass axiom label definition references definition source alternative label Reported term tracker item entity type created parent class ID is about label alt definition is about comment example of usage contributor curation status editor note database cross reference see also Subclass ID Subclass label english exact synonym english broad synonym english narrow synonym english related synonym +ORF1ab GeneID:43740578 GENEPIO:0101134 gene name (SARS-CoV-2) open reading frame 1ab gene (SARS-CoV-2) Instance orf1ab gene (SARS-CoV-2)' GENEPIO:0100155 +ORF1ab GeneID:43740578 GENEPIO:0101135 gene symbol (SARS-CoV-2) orf1ab gene (SARS-CoV-2) Instance orf1ab gene (SARS-CoV-2)' GENEPIO:0100155 +ORF1ab YP_009724389.1 GENEPIO:0101136 protein name (SARS-CoV-2) open reading frame 1ab polyprotein (SARS-CoV-2) Instance replicase polyprotein 1ab (SARS-CoV-2) PR_P0DTD1-1 +ORF1ab YP_009724389.1 GENEPIO:0101137 protein symbol (SARS-CoV-2) Orf1ab protein (SARS-CoV-2) Instance replicase polyprotein 1ab (SARS-CoV-2) PR_P0DTD1-1 +ORF1a YP_009724389.1 GENEPIO:0101140 protein name (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Instance replicase polyprotein 1a (SARS-CoV-2) PR_P0DTC1-1 +ORF1a YP_009724389.1 GENEPIO:0101141 protein symbol (SARS-CoV-2) Orf1a protein (SARS-CoV-2) Instance replicase polyprotein 1a (SARS-CoV-2) PR_P0DTC1-1 +S GeneID:43740568 GENEPIO:0101142 gene name (SARS-CoV-2) surface glycoprotein gene (SARS-CoV-2) Instance Spike gene (SARS-CoV-2)' GENEPIO:0100154 +S GeneID:43740568 GENEPIO:0101143 gene symbol (SARS-CoV-2) s gene (SARS-CoV-2) Instance Spike gene (SARS-CoV-2)' GENEPIO:0100154 +S YP_009724390.1 GENEPIO:0101144 protein name (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) Instance spike glycoprotein (SARS-CoV-2) PR_P0DTC2 +S YP_009724390.1 GENEPIO:0101145 protein symbol (SARS-CoV-2) S protein (SARS-CoV-2) Instance spike glycoprotein (SARS-CoV-2) PR_P0DTC2 +ORF3a GeneID:43740569 GENEPIO:0101146 gene name (SARS-CoV-2) open reading frame 3a gene (SARS-CoV-2) Instance orf3a gene (SARS-CoV-2)' GENEPIO:0100173 +ORF3a GeneID:43740569 GENEPIO:0101147 gene symbol (SARS-CoV-2) orf3a gene (SARS-CoV-2) Instance orf3a gene (SARS-CoV-2)' GENEPIO:0100173 +ORF3a YP_009724391.1 GENEPIO:0101148 protein name (SARS-CoV-2) open reading frame 3a protein (SARS-CoV-2) Instance ORF3a protein (SARS-CoV-2) PR_P0DTC3 +ORF3a YP_009724391.1 GENEPIO:0101149 protein symbol (SARS-CoV-2) Orf3a protein (SARS-CoV-2) Instance ORF3a protein (SARS-CoV-2) PR_P0DTC3 +E GeneID:43740570 GENEPIO:0101150 gene name (SARS-CoV-2) envelope gene (SARS-CoV-2) Instance E gene (SARS-CoV-2)' GENEPIO:0100151 +E GeneID:43740570 GENEPIO:0101151 gene symbol (SARS-CoV-2) e gene (SARS-CoV-2) Instance E gene (SARS-CoV-2)' GENEPIO:0100151 +E YP_009724392.1 GENEPIO:0101152 protein name (SARS-CoV-2) envelope protein (SARS-CoV-2) Instance envelope small membrane protein (SARS-CoV-2) PR_P0DTC4 +E YP_009724392.1 GENEPIO:0101153 protein symbol (SARS-CoV-2) E protein (SARS-CoV-2) Instance envelope small membrane protein (SARS-CoV-2) PR_P0DTC4 +M GeneID:43740571 GENEPIO:0101154 gene name (SARS-CoV-2) membrane glycoprotein gene (SARS-CoV-2) Instance M gene (SARS-CoV-2)' GENEPIO:0100152 +M GeneID:43740571 GENEPIO:0101155 gene symbol (SARS-CoV-2) m gene (SARS-CoV-2) Instance M gene (SARS-CoV-2)' GENEPIO:0100152 +M YP_009724393.1 GENEPIO:0101156 protein name (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) Instance membrane protein (SARS-CoV-2) PR_P0DTC5 +M YP_009724393.1 GENEPIO:0101157 protein symbol (SARS-CoV-2) M protein (SARS-CoV-2) Instance membrane protein (SARS-CoV-2) PR_P0DTC5 +ORF6 GeneID:43740572 GENEPIO:0101158 gene name (SARS-CoV-2) open reading frame 6 gene (SARS-CoV-2) Instance orf6 gene (SARS-CoV-2)' GENEPIO:0100175 +ORF6 GeneID:43740572 GENEPIO:0101159 gene symbol (SARS-CoV-2) orf6 gene (SARS-CoV-2) Instance orf6 gene (SARS-CoV-2)' GENEPIO:0100175 +ORF6 YP_009724394.1 GENEPIO:0101160 protein name (SARS-CoV-2) open reading frame 6 protein (SARS-CoV-2) Instance ORF6 protein (SARS-CoV-2) PR_P0DTC6 +ORF6 YP_009724394.1 GENEPIO:0101161 protein symbol (SARS-CoV-2) Orf6 protein (SARS-CoV-2) Instance ORF6 protein (SARS-CoV-2) PR_P0DTC6 +ORF7a GeneID:43740573 GENEPIO:0101162 gene name (SARS-CoV-2) open reading frame 7a gene (SARS-CoV-2) Instance orf7a gene (SARS-CoV-2)' GENEPIO:0100176 +ORF7a GeneID:43740573 GENEPIO:0101163 gene symbol (SARS-CoV-2) orf7a gene (SARS-CoV-2) Instance orf7a gene (SARS-CoV-2)' GENEPIO:0100176 +ORF7a YP_009724395.1 GENEPIO:0101164 protein name (SARS-CoV-2) open reading frame 7a protein (SARS-CoV-2) Instance ORF7a protein (SARS-CoV-2) PR_P0DTC7 +ORF7a YP_009724395.1 GENEPIO:0101165 protein symbol (SARS-CoV-2) Orf7a protein (SARS-CoV-2) Instance ORF7a protein (SARS-CoV-2) PR_P0DTC7 +ORF7b GeneID:43740574 GENEPIO:0101166 gene name (SARS-CoV-2) open reading frame 7b gene (SARS-CoV-2) Instance orf7b gene (SARS-CoV-2)' GENEPIO:0100177 +ORF7b GeneID:43740574 GENEPIO:0101167 gene symbol (SARS-CoV-2) orf7b gene (SARS-CoV-2) Instance orf7b gene (SARS-CoV-2)' GENEPIO:0100177 +ORF7b YP_009725318.1 GENEPIO:0101168 protein name (SARS-CoV-2) open reading frame 7b protein (SARS-CoV-2) Instance ORF7b protein (SARS-CoV-2) PR_P0DTD8 +ORF7b YP_009725318.1 GENEPIO:0101169 protein symbol (SARS-CoV-2) Orf7b protein (SARS-CoV-2) Instance ORF7b protein (SARS-CoV-2) PR_P0DTD8 +ORF8 GeneID:43740577 GENEPIO:0101170 gene name (SARS-CoV-2) open reading frame 8 gene (SARS-CoV-2) Instance orf8 gene (SARS-CoV-2)' GENEPIO:0100178 +ORF8 GeneID:43740577 GENEPIO:0101171 gene symbol (SARS-CoV-2) orf8 gene (SARS-CoV-2) Instance orf8 gene (SARS-CoV-2)' GENEPIO:0100178 +ORF8 YP_009724396.1 GENEPIO:0101172 protein name (SARS-CoV-2) open reading frame 8 protein (SARS-CoV-2) Instance ORF8 protein (SARS-CoV-2) PR_P0DTC8 +ORF8 YP_009724396.1 GENEPIO:0101173 protein symbol (SARS-CoV-2) Orf8 protein (SARS-CoV-2) Instance ORF8 protein (SARS-CoV-2) PR_P0DTC8 +N GeneID:43740575 GENEPIO:0101174 gene name (SARS-CoV-2) nucleocapsid phosphoprotein gene (SARS-CoV-2) Instance N gene (SARS-CoV-2)' GENEPIO:0100153 +N GeneID:43740575 GENEPIO:0101175 gene symbol (SARS-CoV-2) n gene (SARS-CoV-2) Instance N gene (SARS-CoV-2)' GENEPIO:0100153 +N YP_009724397.2 GENEPIO:0101176 protein name (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) Instance nucleoprotein (SARS-CoV-2) PR_P0DTC9 +N YP_009724397.2 GENEPIO:0101177 protein symbol (SARS-CoV-2) N protein (SARS-CoV-2) Instance nucleoprotein (SARS-CoV-2) PR_P0DTC9 +ORF10 GeneID:43740576 GENEPIO:0101178 gene name (SARS-CoV-2) open reading frame 10 gene (SARS-CoV-2) Instance orf10 gene (SARS-CoV-2)' GENEPIO:0100181 +ORF10 GeneID:43740576 GENEPIO:0101179 gene symbol (SARS-CoV-2) orf10 gene (SARS-CoV-2) Instance orf10 gene (SARS-CoV-2)' GENEPIO:0100181 +ORF10 YP_009725255.1 GENEPIO:0101180 protein name (SARS-CoV-2) open reading frame 10 protein (SARS-CoV-2) Instance putative ORF10 protein (SARS-CoV-2) PR_A0A663DJA2 +ORF10 YP_009725255.1 GENEPIO:0101181 protein symbol (SARS-CoV-2) Orf10 protein (SARS-CoV-2) Instance putative ORF10 protein (SARS-CoV-2) PR_A0A663DJA2 diff --git a/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_genes.json b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_genes.json index 971aaf83..0f40cbf9 100644 --- a/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_genes.json +++ b/assets/virus_ontologyTerms/NC_045512.2/NC_045512.2_ontology_genes.json @@ -9,6 +9,14 @@ "gene_symbol": { "label": "orf1ab gene (SARS-CoV-2)", "uri": "GENEPIO:0101135" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "NCBIGene:43740568": { @@ -21,6 +29,14 @@ "gene_symbol": { "label": "s gene (SARS-CoV-2)", "uri": "GENEPIO:0101143" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "NCBIGene:43740569": { @@ -33,6 +49,14 @@ "gene_symbol": { "label": "orf3a gene (SARS-CoV-2)", "uri": "GENEPIO:0101147" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "NCBIGene:43740570": { @@ -45,6 +69,14 @@ "gene_symbol": { "label": "e gene (SARS-CoV-2)", "uri": "GENEPIO:0101151" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "NCBIGene:43740571": { @@ -57,6 +89,14 @@ "gene_symbol": { "label": "m gene (SARS-CoV-2)", "uri": "GENEPIO:0101155" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "NCBIGene:43740572": { @@ -69,6 +109,14 @@ "gene_symbol": { "label": "orf6 gene (SARS-CoV-2)", "uri": "GENEPIO:0101159" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "NCBIGene:43740573": { @@ -81,6 +129,14 @@ "gene_symbol": { "label": "orf7a gene (SARS-CoV-2)", "uri": "GENEPIO:0101163" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "NCBIGene:43740574": { @@ -93,6 +149,14 @@ "gene_symbol": { "label": "orf7b gene (SARS-CoV-2)", "uri": "GENEPIO:0101167" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "NCBIGene:43740577": { @@ -105,6 +169,14 @@ "gene_symbol": { "label": "orf8 gene (SARS-CoV-2)", "uri": "GENEPIO:0101171" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "NCBIGene:43740575": { @@ -117,6 +189,14 @@ "gene_symbol": { "label": "n gene (SARS-CoV-2)", "uri": "GENEPIO:0101175" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "NCBIGene:43740576": { @@ -129,6 +209,14 @@ "gene_symbol": { "label": "orf10 gene (SARS-CoV-2)", "uri": "GENEPIO:0101179" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } } } \ No newline at end of file From 3043b5a15fa0c4ffa40e939d9b1ebe60407ee210 Mon Sep 17 00:00:00 2001 From: miseminger Date: Mon, 30 Sep 2024 22:36:31 -0700 Subject: [PATCH 047/161] Add gene and strand orientation --- .../NC_045512.2/NC_045512.2.json | 165 ++++++++++++++++-- 1 file changed, 146 insertions(+), 19 deletions(-) diff --git a/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json b/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json index 9c89c9ec..e3224b7a 100644 --- a/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json +++ b/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json @@ -43,6 +43,14 @@ "gene_symbol": { "label": "orf1ab gene (SARS-CoV-2)", "uri": "GENEPIO:0101135" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "ORF1a": { @@ -63,7 +71,9 @@ "aa_start": 1, "aa_end": 4400, "color": "rgb(217, 173, 61)", - "protein_alias": ["ORF1a"], + "protein_alias": [ + "ORF1a" + ], "protein_name": { "label": "open reading frame 1a polyprotein (SARS-CoV-2)", "uri": "GENEPIO:0101140" @@ -91,7 +101,10 @@ "aa_start": 1, "aa_end": 2695, "color": "rgb(80, 151, 186)", - "protein_alias": ["ORF1b", "ORF1ab"], + "protein_alias": [ + "ORF1b", + "ORF1ab" + ], "protein_name": { "label": "open reading frame 1a polyprotein (SARS-CoV-2)", "uri": "GENEPIO:0101140" @@ -114,7 +127,9 @@ "aa_start": 1, "aa_end": 180, "color": "rgb(128,0,128)", - "protein_alias": ["nsp1"] + "protein_alias": [ + "nsp1" + ] }, "nsp2": { "type": "mature_protein_region_of_CDS", @@ -129,7 +144,9 @@ "aa_start": 181, "aa_end": 818, "color": "rgb(128,0,128)", - "protein_alias": ["nsp2"] + "protein_alias": [ + "nsp2" + ] }, "PL_pro": { "type": "mature_protein_region_of_CDS", @@ -144,7 +161,10 @@ "aa_start": 819, "aa_end": 2763, "color": "rgb(128,0,128)", - "protein_alias": ["PL_pro", "PLpro"] + "protein_alias": [ + "PL_pro", + "PLpro" + ] }, "nsp4": { "type": "mature_protein_region_of_CDS", @@ -159,7 +179,9 @@ "aa_start": 2764, "aa_end": 3263, "color": "rgb(128,0,128)", - "protein_alias": ["nsp4"] + "protein_alias": [ + "nsp4" + ] }, "3CL": { "type": "mature_protein_region_of_CDS", @@ -174,7 +196,9 @@ "aa_start": 3264, "aa_end": 3569, "color": "rgb(128,0,128)", - "protein_alias": ["3CL"] + "protein_alias": [ + "3CL" + ] }, "nsp6": { "type": "mature_protein_region_of_CDS", @@ -189,7 +213,9 @@ "aa_start": 3570, "aa_end": 3859, "color": "rgb(128,0,128)", - "protein_alias": ["nsp6"] + "protein_alias": [ + "nsp6" + ] }, "nsp7": { "type": "mature_protein_region_of_CDS", @@ -204,7 +230,9 @@ "aa_start": 3860, "aa_end": 3942, "color": "rgb(128,0,128)", - "protein_alias": ["nsp7"] + "protein_alias": [ + "nsp7" + ] }, "nsp8": { "type": "mature_protein_region_of_CDS", @@ -219,7 +247,9 @@ "aa_start": 3943, "aa_end": 4140, "color": "rgb(128,0,128)", - "protein_alias": ["nsp8"] + "protein_alias": [ + "nsp8" + ] }, "nsp9": { "type": "mature_protein_region_of_CDS", @@ -234,7 +264,9 @@ "aa_start": 4141, "aa_end": 4253, "color": "rgb(128,0,128)", - "protein_alias": ["nsp9"] + "protein_alias": [ + "nsp9" + ] }, "nsp10": { "type": "mature_protein_region_of_CDS", @@ -249,7 +281,9 @@ "aa_start": 4254, "aa_end": 4392, "color": "rgb(128,0,128)", - "protein_alias": ["nsp10"] + "protein_alias": [ + "nsp10" + ] }, "RdRp": { "type": "mature_protein_region_of_CDS", @@ -264,7 +298,10 @@ "aa_start": 4393, "aa_end": 5324, "color": "rgb(128,0,128)", - "protein_alias": ["RdRp", "nsp12"] + "protein_alias": [ + "RdRp", + "nsp12" + ] }, "nsp13": { "type": "mature_protein_region_of_CDS", @@ -279,7 +316,9 @@ "aa_start": 5325, "aa_end": 5925, "color": "rgb(128,0,128)", - "protein_alias": ["nsp13"] + "protein_alias": [ + "nsp13" + ] }, "nsp14": { "type": "mature_protein_region_of_CDS", @@ -294,7 +333,9 @@ "aa_start": 5926, "aa_end": 6452, "color": "rgb(128,0,128)", - "protein_alias": ["nsp14"] + "protein_alias": [ + "nsp14" + ] }, "nsp15": { "type": "mature_protein_region_of_CDS", @@ -309,7 +350,9 @@ "aa_start": 6453, "aa_end": 6798, "color": "rgb(128,0,128)", - "protein_alias": ["nsp15"] + "protein_alias": [ + "nsp15" + ] }, "nsp16": { "type": "mature_protein_region_of_CDS", @@ -324,7 +367,9 @@ "aa_start": 6799, "aa_end": 7096, "color": "rgb(128,0,128)", - "protein_alias": ["nsp16"] + "protein_alias": [ + "nsp16" + ] }, "nsp11": { "type": "mature_protein_region_of_CDS", @@ -339,7 +384,9 @@ "aa_start": 4393, "aa_end": 4405, "color": "rgb(128,0,128)", - "protein_alias": ["nsp11"] + "protein_alias": [ + "nsp11" + ] }, "stem_loop": { "type": "stem_loop", @@ -371,6 +418,14 @@ "gene_symbol": { "label": "s gene (SARS-CoV-2)", "uri": "GENEPIO:0101143" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "S": { @@ -418,6 +473,14 @@ "gene_symbol": { "label": "orf3a gene (SARS-CoV-2)", "uri": "GENEPIO:0101147" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "ORF3a": { @@ -464,6 +527,14 @@ "gene_symbol": { "label": "e gene (SARS-CoV-2)", "uri": "GENEPIO:0101151" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "E": { @@ -511,6 +582,14 @@ "gene_symbol": { "label": "m gene (SARS-CoV-2)", "uri": "GENEPIO:0101155" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "M": { @@ -558,6 +637,14 @@ "gene_symbol": { "label": "orf6 gene (SARS-CoV-2)", "uri": "GENEPIO:0101159" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "ORF6": { @@ -604,6 +691,14 @@ "gene_symbol": { "label": "orf7a gene (SARS-CoV-2)", "uri": "GENEPIO:0101163" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "ORF7a": { @@ -650,6 +745,14 @@ "gene_symbol": { "label": "orf7b gene (SARS-CoV-2)", "uri": "GENEPIO:0101167" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "ORF7b": { @@ -696,6 +799,14 @@ "gene_symbol": { "label": "orf8 gene (SARS-CoV-2)", "uri": "GENEPIO:0101171" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "ORF8": { @@ -742,6 +853,14 @@ "gene_symbol": { "label": "n gene (SARS-CoV-2)", "uri": "GENEPIO:0101175" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "N": { @@ -789,6 +908,14 @@ "gene_symbol": { "label": "orf10 gene (SARS-CoV-2)", "uri": "GENEPIO:0101179" + }, + "strand_orientation": { + "label": "sense strand orientation", + "uri": "GENEPIO:0700002" + }, + "gene_orientation": { + "label": "forward gene orientation", + "uri": "GENEPIO:0700004" } }, "ORF10": { @@ -829,4 +956,4 @@ "type": "INTERGENIC", "color": "rgb(128,128,128)" } -} +} \ No newline at end of file From 363c410d33f4785abf394acffc58e5ef0688e2be Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 1 Oct 2024 11:52:35 -0700 Subject: [PATCH 048/161] Add new functional annotation file --- ...kay_functionalAnnotation_SARSCoV2_v2.0.tsv | 1944 +++++++++++++++++ 1 file changed, 1944 insertions(+) create mode 100644 assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v2.0.tsv diff --git a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v2.0.tsv b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v2.0.tsv new file mode 100644 index 00000000..249c92c4 --- /dev/null +++ b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v2.0.tsv @@ -0,0 +1,1944 @@ +"organism" "reference accession" "reference database name" "nucleotide position" "original mutation description" "nucleotide mutation" "amino acid mutation" "amino acid mutation alias" "gene name" "gene symbol" "protein name" "protein symbol" "measured variant functional effect" "inferred variant functional effect" "viral life cycle functional effect" "measured variant functional effect description" "CVX code" "DrugBank Accession Number" "Antibody Registry ID" "author" "publication year" "URL" "DOI" "PMID" "peer review status" "curator" "mutation functional annotation resource" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has an inhibition rate of virus production by Remdesivir of 0.80." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has a 0.27x fold change in EC50 value with Remdesivir." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "viral load" "" "" "This mutant causes a 0.48x fold change in the infectious virus production rate." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "viral load" "" "" "This mutant causes a 0.41x fold change in the infectious virus production rate." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has an inhibition rate of virus production by Remdesivir of 0.78." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has a 0.66x fold change in EC50 value with Remdesivir." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.526 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.8x reduction in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,22992,23011,23012,23664" "L5F,S477N,E484K,E484K,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 114 test-positive were Iota. Two dose vaccine efficacy against Iota was 95.7 (81.7-99.0%), one dose VE was 88.8 (0.7-98.7)%." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,25186" "L5F,Q1208H" "NC_045512.2:g.13C>T,NC_045512.2:g.3624G>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Gln1208His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Four of the convalescent sera tested showed 4-fold or greater improvement in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21587" "P9S" "NC_045512.2:g.25C>T" "YP_009724390.1:p.Pro9Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2M28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21597" "S12F" "NC_045512.2:g.35C>T" "YP_009724390.1:p.Ser12Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "A variant in low % circulation, predicted to have a similar effect to the experimentally verified S12P, which introduces a new signal peptide, altering cleavage to occur between residues C15 and V16, thereby eliminating the C15-C136 disulfide bond – similarly to escape mutants at positions C15 and C136. This in turn decreases to varying degrees N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600" "S13I" "NC_045512.2:g.38G>T" "YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The S13I mutation dampened binding of 5 mAbs and abrogated binding of 5 additional mAbs out of 11 neutralizing mAbs evaluated. Predicted to shift the signal peptide cleavage site from S13-Q14 to C15-V16, which can affect NTD conformation. PG: in saying S12F does not shift the signal peptide nor affect mAb binding, this manuscript appears to contradict the text of McCallum et al.'s earlier 2021 manuscript stating that S12F *does* affected some mAb binding via putative signal peptide shift." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018" "S13I,W152C" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The B.1.427/B.1.429 S13I/W152C NTD did not bind to any NTD-directed neutralizing mAbs, which are known to target a single antigenic site (antigenic site i), whereas binding of the non-neutralizing S2L20 mAb to the NTD antigenic site iv was not affected by any mutants, confirming proper retention of folding." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.249 (1.7-fold). Neutralization against 10 convalescent plasma was somewhat poorer (3.1-fold)." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 9 plasma collected 15 to 28 days after early 2020 infections, neutralization reduced 4.9-fold for B.1.427/B.1.429 compared to wildtype (D614G). In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.427/B.1.429 pseudotyped virus, as well as WT and other VOCs." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Swab samples N/NP viral RNA is approximately 2-fold higher in B.1.427/B.1.429 than in non-variant viruses." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using HIV pseudotype: Neutralization potency of 11 Moderna mRNA1273-elicited plasma (7-27 days post-2nd dose) was reduced ~2.8-fold compared to wildtype (D614G) S. It was reduced ~4-fold in 14 Pfizer/BioNtech BNT162b2-elicited plasma (7-27 days post-2nd dose). Using VSV pseudotype: we observed a 3-fold average reduction of Pfizer/BioNtech BNT162b2-elicited plasma neutralizing activity." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Antibody neutralization assays showed 6.7-fold resistance against 7/8 convalescent plasma." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Lineages bearing these spike mutations comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the ""California"" or ""West Coast"" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI:1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020." "" "" "" "Peng" "2021" "https://doi.org/10.1093/cid/ciab283" "doi:10.1093/cid/ciab283" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "14 of 34 RBD-specific mAbs showed reduced neutralization to the B.1.427/B.1.429 variant pseudotype." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.427/429 reduced 2.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 2.3x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "6 of 11 (55%) vaccine recipients (Moderna or Pfizer), showed 2x reduction in neutralization to a B.1.429 lineage virus." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 2.7x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403,25135" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G,K1191N" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys1191Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for CAL.20C (B.1.429), and a slight decrease in CD8+ percentage (p=0.0201) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21604,21604" "Q14H,Q14H" "NC_045512.2:g.42G>C,NC_045512.2:g.42G>T" "YP_009724390.1:p.Gln14His,YP_009724390.1:p.Gln14His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21605" "C15R" "NC_045512.2:g.43T>C" "YP_009724390.1:p.Cys15Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21606" "C15F" "NC_045512.2:g.44G>T" "YP_009724390.1:p.Cys15Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates neutralization by N-terminal-domain-targeting mAbs 4-19. Impairs neutralization by N-terminal-domain-targeting mAbs 4A8 and 2-17." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggetsing that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132" "L18F,T20N,P26S,D138Y,R190S" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The neutralization titer of NTD-binding mAb159 was 133-fold reduced on P.1 compared to Victoria (~wild type), with only 64% neutralization at 10 μg/mL. Residues 20, 18, and 138 form a cluster underlying the 245–259 loop, which inserts into a groove between the light and heavy chains of Fab 159. In addition, the N-terminal residues preceding residue 18 interact with the antibody and may be perturbed. Given that there is likely a single supersite (""i"") for potent NTD-binding antibodies, the binding of many of these are likely affected. Using 20 potent (primaruly anti-RBD) antibodies, neutralization was measured by a focus reduction neutralization test (FRNT) and compared with neutralization of Victoria (~wild type) and variants B.1.1.7 and B.1.351. Compared to Victoria neutralization by the mAbs was significantly impacted by P.1, with 12/20 showing > 10-fold reduction in FRNT50 titer and a number showing complete knockout of activity. The results with P.1 showed a greater impact compared to B.1.1.7 but were, as expected, similar to those with B.1.351." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In convalescent sera one month or more post-infection in Spring 2020, an average 6.5x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.4x decrease against the full P.1 type vs WA-1 was observed, with better full P.1 ID50 reciprocal value compared to the 10-mutation model." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Amongst RBD-targeting Emergency Use Authorized monoclonal antibody treatments CB6, LY-CoV555 and REGN10933 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1, but REGN10987 activity remains strong. RBD-targeting monoclonal antibodies 2-15 and C121 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. N terminal domain targeting monoclonal antibodies 5-7, 4-8, 4-18 and 2-17 have abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the “up” position." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 12 Moderna vaccinee sera 15 days post second dose (43 days since first vaccination), an average 2.8x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 4.8x decrease against the full P.1 type vs WA-1 was observed, though overall with a higher ID50 reciprocal value. In 10 Pfizer vaccinee sera 7 days or more post second dose (28 days or more since first vaccination), an average 2.2x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.8x decrease against the full P.1 type vs WA-1 was observed, with similar variant ID50 reciprocal value." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Gamma (P.1) variant is 0.6x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Three healthcare workers (29-50yo) had confirmed P.1 [Gamma] re-infection in the Amazonas region of Brazil 3-9 months after initial infection from viruses with distinct lineage from P.1, but mild symptoms upon re-infection and evidence for infectiousness during re-infection." "" "" "" "Naveca" "2021" "https://doi.org/10.21203/rs.3.rs-318392/v1" "doi:10.21203/rs.3.rs-318392/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "After a 128 day interval, a patient in Sao Paulo State, Brazil reinfected with P.1 (first episode likely predates P.1 emergence). Both cases were fairly mild (difficulty breathing, tiredness, dizziness and fatigue)." "" "" "" "Malta Romano" "2021" "https://doi.org/10.1590/S1678-9946202163036" "doi:10.1590/S1678-9946202163036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 4.1x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 349 test-positive were Gamma. Two dose vaccine efficacy against Gamma was 95.5 (90.9-97.8%), one dose VE was 74.2 (43.8-88.1%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x cleavage of S2 relative to WA1 (D614G) wildtype by Gamma variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but H655Y is upstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 3.0x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped P.1 virus has reduced neutralization activity vs wild type: 6.7x (30 sera Pfizer median 9 days post 2nd dose) and 4.5x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Unlike wild type or B.1.1.7, P.1 lineage virus was able to infect and replicate in common lab mouse strains, with high titer." "" "" "" "Montagutelli" "2021" "https://doi.org/10.1101/2021.03.18.436013" "doi:10.1101/2021.03.18.436013" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.248 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07. B.1.1.248 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.248 variant constellation in 10 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples, P=0.0020." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 16.6% in this B.1.1.248 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly lower against B.1.1.248 variant constellation in sera tested from most of the 15 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.7 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0039 for mild resistance." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Among 46,884 HCWs in Manaus, Brazil vaccinated with at least one dose of CoronaVac, a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%; 95% CI, 11.3 - 71.4) in the odds of symptomatic SARS-CoV-2 infection was observed during the period 14 days or more after receiving the first dose. Estimated vaccine effectiveness of at least one dose against any SARS-CoV-2 infection was 35.1% (95% CI, −6.6 - 60.5) in the same time period." "" "" "" "Hitchlings" "2021" "https://doi.org/10.1101/2021.04.07.21255081" "doi:10.1101/2021.04.07.21255081" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "VSV pseudotype P.1 entry mediated by the S proteins of the P.1 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Cell fusion proficiency was slight impaired. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.15x *increase* in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "VSV pseudotype P.1 showed 4.8-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections)." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Neutralizing antibodies that were generated following a mild infection with SARS-CoV-2 B.1.128 were effective in vitro, and likely protective, against the SARS-CoV-2 P.1. variant in the majority of individuals based on 60 convalescent sera tested." "" "" "" "Mendes-Correa" "2021" "https://doi.org/10.1101/2021.05.11.21256908" "doi:10.1101/2021.05.11.21256908" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype P.1 showed slight decrease in cell entry relative to wild type in 262T and 263T-ACE2 (kidney) cell lines. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for P.1 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the P.1 variants used, using the most popular as a stand in]" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "P.1 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with Lilly mAb combination LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of P.1. There was also escape from neutralization of P.1 by REGN10933 (one of 2 in Regeneron's mAb cocktail) and a modest reduction in neutralization of P.1 by AstraZeneca's AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized P.1 with all reaching a plateau at 100% neutralization; interestingly, ADG30 showed a slight increase of neutralization of P.1. S309 Vir was largely unaffected, although for several viruses, including P.1, the antibody failed to completely neutralize, conceivably reflecting incomplete glycosylation at N343, since the sugar interaction is key to binding of this antibody." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against P.1 at various time points using pseudovirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 85%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "PBMCs of 11 mild COVID-19 patients collected 38-80 days after symptom onset were stimulated with the 15-mer peptide pools (w/ 10 residue overlaps) from the wholle viral proteome, showing no significant CD4+ cell count effect for P.1, and a slight increase in CD8+ percentage (p=0.0195) by Activation Induced Marker (AIM) assay (cellular immunity measurement). [in the text, this increase is not noted as signficant, even though p=0.05 is used elsewhere in the text as a signficance threshold]" "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 256 for B.1.1.7 virus. Compare to somewhat stronger neutralization titer for wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "L18F,T20N,P26S,D138Y,R190S,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The relative transmissibility of P.1 estimated at the national level (Italy) varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. PG: variant list has been abbreviated due to mixed K417 bases in this lineage, potential miscalls of deletions" "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21801,22206,22334,22600,22600,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22986,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D80A,D215G,W258R,R346S,R346S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,A475V,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ala475Val,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments and mutations from variants of concern completely ablates neutralization in 19 of 21 convalescents plasma collected mean 1.3 months post infection. [actual Y145del from manuscript substituted with more common Y144del description]" "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801" "L18F,D80A" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The L18F and D80A of the B.1.351 lineage lead to reconfiguration of the N-terminal segment despite the disulfide between Cys16 and Cys136 that partly anchors the N-terminal peptide. The most consequential changes are probably from the triple residue deletion... which causes a shift of the nearby loop 144-155 and must also reconfigure the adjacent disorder loop (residues 246-260), both of which form part of the neutralizing epitopes...bringing large changes in the antigenic surface in this region." "" "" "" "Cai" "2021" "https://doi.org/10.1101/2021.04.13.439709" "doi:10.1101/2021.04.13.439709" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The 501Y.V2 to first wave IC50 ratio ranged from 6 to 200-fold. Averaging across all 7 participant convalescent sera highlighted the dramatic decrease in sensitivity to neutralization of authentic 501Y.V2 variants. PG: I'm purposefully ignoring D614G and A701V as contributors" "" "" "" "Cele" "2021" "https://doi.org/10.1038/s41586-021-03471-w" "doi:10.1038/s41586-021-03471-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike)." "" "" "" "Riddell" "2021" "https://doi.org/10.1101/2021.04.17.440246" "doi:10.1101/2021.04.17.440246" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike)." "" "" "" "Riddell" "2021" "https://doi.org/10.1101/2021.04.17.440246" "doi:10.1101/2021.04.17.440246" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~7-fold reduction in B.1.351 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pzifer vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1), but were all infected before 14 days post second vaccination." "" "" "" "Kustin" "2021" "https://doi.org/10.1101/2021.04.06.21254882" "doi:10.1101/2021.04.06.21254882" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 8 for B.1.351 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "A 1.8-fold drop in FRNT50 for B.1.351 was observed in 44 sera collected between 1 and 301 post-infection." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals (5/9) and recipients of a only a single dose of mRNA vaccine (10/11) – heterotypic neutralization dropped to negligible levels, particularly against B.1.351." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "B.1.351 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of B.1.351. There was also escape from neutralization of B.1.351 by REGN10933 and a modest reduction in neutralization of B.1.351 by AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized B.1.351." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed for B.1.351 a CD4+ cell count decrease (29%, p=0.00063) as well as CD8+ (33%, p=0.0016) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms had mean ~6x reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.054x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR22 molecule had a 1.57x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 0.036x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.351. We observed an increase (relative to D614G) in binding of soluble ACE2 to B.1.351, and to a much gearter extent to B.1.1.7, which both carry the N501Y mutation (see Fig 3)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: while B.1.1.7 and D614G showed neutralization by nasal swab from only one different previously infected vacinee neutralizing at weeks 3 and 6, B.1.351 showed zero neutralization at either time point in any sample (and relatively impaired serum neutralization)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "[Contrary to how this paper has been cited, Voysey et al. do NOT show evidence of decreased effectiveness of ChAdOx1 (AstraZeneca) against the South African B.1.351 lineage. Insufficient numbers reaching the primary study endpoint were available in that arm of the vaccine study to report any statistics from the South African participants. Additionally, the study period of the paper ended in November 2020, while the earliest reported case of this lineage is October (covariants.org), only becoming dominant by mid-November.]" "" "" "" "Voysey" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.07x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 8.2x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Sera from individuals who have been infected with Delta does not have strong neutralising activity against Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v2 reduced 7.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 6.3x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Pseudotype lentivirus for the full B.1.351 Spike variant list shows increase affinity for ACE2 as measured by IC50. This is in contrast to B.1.1.7 which showed no major change, indicating that the shared N501Y mutation is the driver of affinity change, attentuated in the B.1.1.7 mutatioon set, but maintained in the B.1.351 lineage." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v2 virus has reduced neutralization activity vs wild type: 41.2x (30 sera Pfizer median 9 days post 2nd dose) and 20.8x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Beta Variant B.1.351 RBD significantly better than w.t. SARS-CoV-2 RBD. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Encouragingly, we find that the majority of T cell responses in recipients of two doses of the BNT162b2 vaccine are generated by epitopes that are invariant between the [wildtype] and two of the current variants of concern (B.1.1.7 and B.1.351). In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals and recipients of a only a single dose of mRNA vaccine – heterotypic neutralization dropped to negligible levels, particularly against B.1.351." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.351 pseudotyped virus model ablates neutralization by RBD-directed mAbs CB6, 4-20, 2-4, 2-43, 910-30, 2-302-15, LY-Cov555, C121. B.1.351 pseudotyped virus model severely impairs neutralization by RBD-directed mAb 1-20. B.1.351 pseudotyped virus model impairs neutralization by RBD-directed mAb REGN10933. B.1.351 pseudotyped virus model ablates neutralization by N-terminal-domain-directed mAbs 5-24, 4-8, 4A8, 4-19. B.1.351 pseudotyped virus model severely impairs neutralization by N-terminal-domain-directed mAb 2-17. B.1.351 pseudotyped virus model impairs neutralization by N-terminal-domain-directed mAb 5-7. PG: Live virus data for the same mAbs is similar, but 1-20 becomes severally impaired, REGN10933 activity is ablated, and Brii-196 becomes impaired." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 16/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.351, with similar results for the live virus." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Beta neutralizing antibodies is 0.899x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "3.2x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Beta neutralizing antibodies is 0.803x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.351 sample. Contrast this with 1.4-fold reduction for just the pseudovirus combination of ""key"" B.1.351 mutations K417N+E484K+N501Y. WA1 and B.1.351 FRNT50 titers correlated weakly at the individual level, with some individual’s serum potently neutralizing WA1 while having FRNT50 for B.1.351 below the assay limit of detection (1:20)." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664,21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 6.7x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664,21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 99.7x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with all key mutations from B.1.351 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting some synergy between the mutations to decrease cell entry fitness (i.e. cell entry is liklely not the driver of this lineage's dominance)." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,23060,23061,23062,23062,23063,23063,22810,22810,22811,22812,22813,22813,22813,23011,23012,23399,23401,23401,23402,23403,23403" "L18F,D80A,D215G,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The most significant loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against authentic B.1.351 lineage virus (9.2-fold). Neutralization against 10 convalescent plasma was poorer (18.7x)." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks." "" "" "" "Meister" "2021" "https://doi.org/10.1093/infdis/jiab260" "doi:10.1093/infdis/jiab260" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Parana state of Brazil, patients aged 20-29 years experienced a tripling of their case fatality rate (CFR), from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling comparing February to January in 2021. Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil. [this is somewhat indirect evidence that assume greatly increasing proportion of P.1 cases in March (70%) compared to February, but the first official ID of P.1 in Parana state (Feb 16th) may be due to testing procedures rather than actual prevalence]" "" "" "" "Santos de Oliviera" "2021" "https://doi.org/10.1101/2021.03.24.21254046" "doi:10.1101/2021.03.24.21254046" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22915,22915,22916,22916,22917,22917,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,L452R,L452R,L452R,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 (Pfizer) vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains." "" "" "" "Mallm" "2021" "https://doi.org/10.1101/2021.04.27.21254849" "doi:10.1101/2021.04.27.21254849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22224,22227,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Delta (B.1.617.2) shows mean 2.1x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22224,22227,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Delta (B.1.617.2) shows 3.64x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "T19R,T95I,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this lineage defining mutation combination from B.1.617.3 conferred a ~4.5x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "T19R,T95I,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this lineage defining mutation combination from B.1.617.3 increased syncytium formation ~2.3x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "T19R,T95I,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this lineage defining mutation combination from B.1.617.3 conferred a ~11.8x drop in neutralization (NT50) [suggesting role for T19R and T95I in half the sera]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,23399,23401,23401,23402,23403,23403" "T19R,T95I,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22028,22915,22915,22916,22916,22917,22917,23604,23604,23399,23401,23401,23402,23403,23403,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,E156del,L452R,L452R,L452R,L452R,L452R,L452R,P681R,P681R,D614G,D614G,D614G,D614G,D614G,D614G,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4.5x cleavage of S2 relative to WA1 (D614G) wildtype by Delta (B.1.617.2) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~3.5x for closely related Kappa B.1.617.1 also with P681R at the cleavage site)." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. [Mutation list in publication appears to contain a typo with R158del instead of R158G]" "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Modelling the Delta variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increased 11x relative to wild type (15.3 vs 1.4). [del ~157 truncated due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a coinfection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 4.0x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.020x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.10x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 2.6x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In primary human airway epithelial cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 1.9x relative to wild type (2.7 vs 1.4). This is the Delta variant with the P681R furin cleavage site mutation absent. [del ~157 truncated due to ambiguity]" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Delta Variant B.1.617.2 RBD or w.t. SARS-CoV-2 RBD with nearly equal potency determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Delta neutralizing antibodies is 0.952x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Delta neutralizing antibodies is 0.872x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Plasma neutralizing activity was also assessed against SARS-CoV-2 Delta, Omicron BA.1, BA.2 and BA.4/5 variants using viruses pseudotyped with appropriate variant spikeproteins. Delta breakthrough infection resulted in 15-fold increased neutralizing titers." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Plasma neutralizing activity in 49 participants was measured using HIV-1 pseudotyped with the 100 WT SARS-CoV-2 spike protein. Delta breakthrough infection resulted in 11-fold increased geometric mean half-maximal neutralizing titer (NT50)." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 507 pM for binding to the Delta B.1.617.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001)." "" "" "" "Chia" "2021" "https://doi.org/10.1101/2021.07.28.21261295" "doi:10.1101/2021.07.28.21261295" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.92x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001)." "" "" "" "Chia" "2021" "https://doi.org/10.1101/2021.07.28.21261295" "doi:10.1101/2021.07.28.21261295" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccination of health care workers in Delhi was started in early 2021, with the ChdOx-1 (Astra Zeneca) vaccine. Surveillance has suggested B.1.1.7 dominance in the Delhi area during early 2021, with growth of B.1.617 since March 2021. During the wave of infections during March and April an outbreak of SARS-CoV-2 was confirmed in 33 vaccinated staff members at a single tertiary centre (age 27-77 years). Sequencing revealed that 16/33 were B.1.617.2, with a range of other B lineage viruses including B.1.1.7 for the rest except one A lineage case. Importantly no severe cases were documented in this event." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "The incidence rate of Covid-19 during the Delta-dominant period (Jul-Aug 2021) was lower for late vaccinated (49.0/1000 person-years) [formerly placebo] versus early vaccinated (77.1/1000 person-years) participants in the Moderna mRNA-1273 Phase 3 trials, representing a 36.4% VE reduction (95% CI 17.1%-51.5%). There were fewer severe Covid-19 cases in the late group (6; 6.2/1000 person-years) than early (13; 3.3/1000 person-years), representing a 46.0% reduction (95% CI −52.4%-83.2%). Three Covid-19 related hospitalizations occurred with two resulting deaths in the early group." "" "" "" "Baden" "2021" "https://doi.org/10.1101/2021.09.17.21263624" "doi:10.1101/2021.09.17.21263624" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance." "" "" "" "Twohig" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.89x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance." "" "" "" "Twohig" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Case 62541 cluster in Singapore included a fully vaccinated nurse 2 months post-vaccine [likely Pfizer based on dates and supply], and a doctor of unknown vaccine status. This cluster was caused by a B.1.617.2 virus [via crossreference to" "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Delta Molnupiravir (MK-4482) had ~4x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Denmark, for the period Jan 1 to Jun 27, 2021, Delta variant was associated with increased an risk ratio of 2.83 [95% CI 2.02–3.98] for hospitalization." "" "" "" "Bager" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.2 aka Delta) showed a 2.34x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Delta (B.1.617.2) has an IC50 fold change of 0.87x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Delta (B.1.617.2) has an IC50 fold change of 0.15x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Delta (B.1.617.2) has an IC50 fold change of 46.5x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Delta (B.1.617.2) has an IC50 fold change of 0.57x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Delta (B.1.617.2) variant is 0.6x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,23399,23401,23401,23402,23403,23403" "T19R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21627" "T22I" "NC_045512.2:g.65C>T" "YP_009724390.1:p.Thr22Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain, frequently observed in various human infection lineages, reduces the tropism of SARS-CoV-2 in F81 (cat kidney, Felis catus) and BHK-21 (golden hamster kidney, Mesocricetus auratus) cell line cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21648" "T29I" "NC_045512.2:g.86C>T" "YP_009724390.1:p.Thr29Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21717,21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23011,23012,23399,23401,23401,23402,23403,23403,23593,23593,24224" "Q52R,A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,F888L" "" "YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.525 reduced 4.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21717,23011,23012,23593,23593,24224" "Q52R,E484K,E484K,Q677H,Q677H,F888L" "" "YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The B.1.525 appears to have poor transmissibility when in competition with B.1.1.7 and other circulating strains in Denmark (early 2021)." "" "" "" "Albertsen" "2021" "https://www.covid19genomics.dk/2021-05-08_data-overview.html#b1525" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21752,21752" "W64R,W64R" "NC_045512.2:g.190T>A,NC_045512.2:g.190T>C" "YP_009724390.1:p.Trp64Arg,YP_009724390.1:p.Trp64Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21759" "H66R" "NC_045512.2:g.197A>G" "YP_009724390.1:p.His66Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent, especially on a D614 wildtype background." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Neutralization activity of almost all Moderna Phase 1 sera tested actually *increased*." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This deletion outside the receptor binding domain in pseudotyped VSV promoted the capacity of pseudotyped VSV to transduce black flying fox (Pteropus alecto) kidney PabKi.1 cells (17.8%) to a level twice that of human epithelial-like Huh-7 cells (9.8%)" "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No notable change in neutralization efficiency, despite N439K by itself showing a ~2x decrease on average in 16 health workers' convalescent sera." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduces neutralization by structurally unmapped mAb COVA1-21 (cluster XI)." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization activity of convalescent sera tested decreased ~2x with this B.1.1.7 pseudotyped virus." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization activity of almost all convalescent sera tested decreased ~2x." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "The delH69/V70 enhances viral infectivity, indicating its effect on virus fitness is independent to the N501Y RBM change [with which it is found in lineage B.1.1.7] Possibly arisen as a result of the virus evolving from immune selection pressure in infected individuals and possibly only one chronic infection in the case of lineage B.1.1.7." "" "" "" "Kemp" "2020" "https://doi.org/10.1101/2020.12.14.422555" "doi:10.1101/2020.12.14.422555" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was somewhat lower against B.1.1.7 in sera tested from most of the 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.7 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2489." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.1.7 sample. Contrast this with 1.3-fold reduction for just the pseudovirus combination of ""key"" B.1.1.7 mutation N501Y." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, much closer to D614G activity level than Y453F alone, suggesting compensatory effects between the deletion and the mutation in human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild to modest decrease in infection rate amongst the cells, suggesting a net mild negative effect on human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing moderate decrease in infection rate amongst the cells, significantly lower than the deletion or Y453F alone, or their combination, suggesting a synergistic effect on poorer human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920,23399,23401,23401,23402,23403,23403,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,D614G,D614G,D614G,D614G,D614G,D614G,M1229I,M1229I,M1229I" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.298 virus has reduced neutralization activity vs wild type: 1.4x (30 sera Pfizer median 9 days post 2nd dose) and 1.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from Mink Cluster 5 was neutralized more easily than D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with all key mutations from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (~50%) decrease in infection rate amongst the cells, suggesting that this anthropozoonotic event is driven by other factors at the expense of human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells, markedly higher infectivity than either mutation alone, suggesting a synergistic net neutral effect on human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23011,23012,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7+E484K reduced 2.8x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Compare with 1.2x reduction for B.1.1.7 without E484K." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23011,23012,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23011,23012,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization capacity GMT of 27 subjects' sera post-infection was markedly worse against B.1.1.7 + E484K than the lineage alone, with a 11.4x drop." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23011,23012,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." "" "" "" "van Loon" "2021" "https://doi.org/10.1101/2021.04.15.21255389" "doi:10.1101/2021.04.15.21255389" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, moreso than this combination with the addition of P681H." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "A higher proportion of cases infected with the B.1.1.7 variant were hypoxic on admission compared to other variants (70.0% vs 62.5%, p=0.029), in London between March 13th 2020 and February 17th 2021 (400 B.1.1.7 cases out of 1470 total sequenced)." "" "" "" "Snell" "2021" "https://doi.org/10.1101/2021.03.16.21253377" "doi:10.1101/2021.03.16.21253377" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation combination causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." "" "" "" "van Loon" "2021" "https://doi.org/10.1101/2021.04.15.21255389" "doi:10.1101/2021.04.15.21255389" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x). PG: these effects are laregly missing in the deletion-alone data" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively." "" "" "" "Schuit" "2021" "https://doi.org/10.1093/infdis/jiab171" "doi:10.1093/infdis/jiab171" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks." "" "" "" "Meister" "2021" "https://doi.org/10.1093/infdis/jiab260" "doi:10.1093/infdis/jiab260" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%)." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion)." "" "" "" "Marquez" "2021" "https://doi.org/10.1017/ice.2021.195" "doi:10.1017/ice.2021.195" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion)." "" "" "" "Marquez" "2021" "https://doi.org/10.1017/ice.2021.195" "doi:10.1017/ice.2021.195" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 2.6x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 1 (B.1.1.7) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Live virus was tested ex vivo in reconstituted brochial epithelium, and out competed wild type." "" "" "" "Touret" "2021" "https://doi.org/10.1101/2021.03.22.436427" "doi:10.1101/2021.03.22.436427" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "NTD-specific nAbs showed a substantial (3-450x) decrease in neutralization potency against the recently reported highly transmissible B.1.1.7 variant of concern, whereas RBD-specific nAbs were either unaffected or showed lower decreases in potency." "" "" "" "Graham" "2021" "https://doi.org/10.1016/j.immuni.2021.03.023" "doi:10.1016/j.immuni.2021.03.023" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2.5x cleavage of S2 relative to WA1 (D614G) wildtype by Alpha variant variant as measured by mass spectrometry of Vero-TMPRSS culture." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Modelling the Alpha variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 3.9x relative to wild type (5.4 vs 1.4). This is less efficient than Delta (11x vs wildtype using a P681R mutation instead). [del ~144 changed due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a co-infection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "clinical indicators" "" "" "After adjusting for the age factor, in a prospective Chinese cohort study B.1.1.7 variant infection (compared to B.1.140) was the risk factor for C-reactive protein (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), Serum amyloid A (0.011, 5.031, [1.459, 17.354]), Creatine Kinase (0.034, 4.34, [0.05, 0.91]), CD4+ T lymphocyte (0.029, 3.31, [1.13, 9.71]), and Ground Glass Opacity (0.005, 5.418, [1.656, 17.729])" "" "" "" "Song" "2021" "https://doi.org/10.1101/2021.05.04.21256655" "doi:10.1101/2021.05.04.21256655" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 2/20 (10%) samples showed >10x reduction (sera collected ~1mo post Jan 2020 first wave in China). Neutralizing antibody titers of 8/20 samples (40%) decreased below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.7 pseudotyped virus model impairs binding by RBD-directed mAb 910-30. B.1.1.7 pseudotyped virus model abolishes N-terminal-domain-directed mAbs 5-24, 4-8, and 4A8. B.1.1.7 pseudotyped virus model impairs binding by N-terminal-domain-directed mAbs 2-17, 4-19, 5-7." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Lessens the potency of mAbs COVA2-17 (~5x, similar to N501Y alone), COVA1-12 (~11x) and COVA1-21 (>100x), which do not compete allosterically." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Alpha Variant B.1.1.7 RBD significantly better than GenScript IgG FL18-740 w.t. ACE-2 mAB. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20x resistence to mAb CQ038 by B.1.1.7 pseudotyped virus" "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 1.7x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.1.7. We observed a dramatic increase (relative to D614G) in binding of soluble ACE2 to B.1.1.7, and to a lesser extent to B.1.351, which both carry the N501Y mutation (see Fig 3)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020. Possible reinfections were identified in 249 (0.7% [95% CI 0.6-0.8]) of 36509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants." "" "" "" "Graham" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM for binding to the Alpha B1.1.7. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively." "" "" "" "Schuit" "2021" "https://doi.org/10.1093/infdis/jiab171" "doi:10.1093/infdis/jiab171" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Second infection in December 2020 with B.1.1.7 after April 2020 initial infection with B.2 in a 78-year-old man with a history of Type 2 diabetes mellitus, diabetic nephropathy on hemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnea, ischemic heart disease, with no history of immunosuppression." "" "" "" "Harrington" "2021" "https://doi.org/10.1093/cid/ciab014" "doi:10.1093/cid/ciab014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "aerosolization" "" "" "Alpha variant cases in a large campus study showed fine-aerosol shedding amongst unmasked participants remained significantly greater for alpha variant infections (18-fold, 95% CI, 3.4 to 92-fold) after adjusting for the increased viral RNA in MTS and saliva, the number of coughs during sampling sessions, and symptom. After controlling for the effect of masks and numbers of coughs during sampling, alpha variant infection was associated with a 100-fold (95% CI, 16 to 650-fold) increase in coarse- and a 73-fold (95% CI, 15 to 350-fold) increase in fine-aerosol RNA shedding." "" "" "" "Adenaiye" "2021" "https://doi.org/10.1093/cid/ciab797" "doi:10.1093/cid/ciab797" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "First documented cases of domestic cat and dog infections with the B.1.1.7 strain." "" "" "" "Hamer" "2021" "https://doi.org/10.1111/tbed.14122" "doi:10.1111/tbed.14122" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaulated against VSV pseudotypes: neutralized D614G at week 2, whereas B.1.1.7 started to be neutralized at week 3, although less efficiently than D614G. B.1.1.7 and D614G strains were similarly neutralized at week 4 (1 week after booster dose)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Alpha Molnupiravir (MK-4482) had ~2.75x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM analysis of B.1.1.7 demonstrates an increased propensity for 'up', receptor accessible conformation of the Spike protein trimer." "" "" "" "Cai" "2021" "https://doi.org/10.1101/2021.04.13.439709" "doi:10.1101/2021.04.13.439709" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "NVX-CoV2373 [Novavax] vaccine in phase 3 trial was 89.7% (95% CI, 80.2-94.6) effective in preventing COVID-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8-99.5) and 86.3% (71.3-93.5) against the prototype strain and B.1.1.7 variant, respectively." "" "" "" "Heath" "2021" "https://doi.org/10.1101/2021.05.13.21256639" "doi:10.1101/2021.05.13.21256639" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the 47D10. Alpha (B.1.1.7) has an IC50 fold change of 0.40x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.44x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Alpha (B.1.1.7) has an IC50 fold change of 1.19x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.39x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 virus has reduced neutralization activity vs wild type: 2.1x (30 sera Pfizer median 9 days post 2nd dose) and 2.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Note that Y145del was actually noted in the paper as the effect of their DNA construct, but this is equivalent at the protein level to the more commonly annotated Y144del." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization assays of B.1.1.7 virus showed a reduction of 2.5-fold (14 days post 2nd dose AstraZeneca, n=15), 2.1-fold (28 days post 2nd dose AstraZeneca, n=10), and 3.3-fold (7-17 days post 2nd dose Pfizer-BioNTech, n=25). [D1119H was included in the original paper, assumed typographical error and changed to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We observed a sharp decline in cases when ∼50% of the elderly population was 2 weeks beyond their first vaccination dose and at a time point during which the B.1.1.7 variant gained transmission dominance. In support of this finding, it was suggested that, after the first vaccination dose, more than 70% of patients develop neutralization antibodies,15 and the vaccine efficiency can reach 85%." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Alpha (B.1.1.7) variant is 1.0x fold the wildtype in 42 COVI." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.1.7 lineage effectiveness was observed as 29.5% (95% CI [22.9,35.5]) against infection, and 54.1% against severe/critical/fatal disease (95% CI [26.1-71.9]). Two weeks or more after 2nd dose, effectiveness climbed to 89.5% [85.9,92.3] against infection, and 100% against severe/critical/fatal disease (95% CI [81.7,100])." "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,24506" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,S982A" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Lilly's LY-CoV16 showed marked reduction in neutralization of B.1.1.7." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Sera neutralized the B1.1.7 isolate with a lower potency (2-fold; 95% CL: 1.5 – 3-fold), and those with the lowest homotypic neutralizing potency had undetectable heterotypic potency (2/25)." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23709,23604,23604,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,T716I,P681H,P681H,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific replication effects" "" "" "In this report, by using a lower infectious dose, we demonstrate that B.1.1.7 (cultured sample Hong Kong/HKPU-00015/2021) exhibits higher infectivity and/or replication efficiency in the nasal epithelium. (Hamster model of infection)" "" "" "" "Mok" "2021" "https://doi.org/10.1101/2021.04.19.440414" "doi:10.1101/2021.04.19.440414" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7." "" "" "" "Graham" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization capacity GMT of 27 subjects' sera post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The mortality hazard ratio associated with infection with [B.1.1.7] compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community (54906 matched pairs of participants who tested positive for SARS-CoV-2 in pillar 2 between 1 October 2020 and 29 January 2021). In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases." "" "" "" "Challen" "2021" "https://doi.org/10.1136/bmj.n579" "doi:10.1136/bmj.n579" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7." "" "" "" "Graham" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036)." "" "" "" "Song" "2021" "https://doi.org/10.1101/2021.05.04.21256655" "doi:10.1101/2021.05.04.21256655" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies." "" "" "" "Muik" "2021" "https://doi.org/10.1126/science.abg6105" "doi:10.1126/science.abg6105" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies." "" "" "" "Muik" "2021" "https://doi.org/10.1126/science.abg6105" "doi:10.1126/science.abg6105" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "20/29 sera after the first dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 variant of 3.2 ± 5.7. After the second dose, the GMT was markedly increased compared with the first-dose titres, with a fold change of 1.9 ± 0.9 (mean ± s.d.). Neutralization GMT of 27 subjects post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype B.1.1.7 showed no significant difference in cell entry relative to wild type in 6 cell lines. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020, Rt of B.1.1.7 was 1.35x (95% CI 1.02-1.69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant." "" "" "" "Graham" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Slight neutralization improvement on average in 16 health workers' convalescent sera." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, but to a smaller extent than N501Y and the deletion alone." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "These key B.1.1.7 mutations as a combination neutralized slightly less well than D614G and this was noticeable in the lack of sera with high neutralizing titer for the viruses across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22679,22679,23521,23521,23522,23524,23524,23525,23525,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,23060,23061,23062,23062,23063,23063,22879,22879,22881,22882,22882,22882,23071,23071,23074,23074,23075,23075,22992,22995,22810,22810,22811,22812,22813,22813,22813,23018,22576,22577,22578,22783,22783,22784,22785,22786,22786,23604,23604,22686,23053,23053,23054,23054,23055,23055,22992,23009,23010,23012,23013,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,S373P,S373P,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,R408S,P681H,P681H,S375F,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 13.0-fold lower (95% CI: 4.2x-4.6x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22679,22679,23521,23521,23522,23524,23524,23525,23525,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,23060,23061,23062,23062,23063,23063,22879,22879,22881,22882,22882,22882,23071,23071,23074,23074,23075,23075,22992,22995,22810,22810,22811,22812,22813,22813,22813,23018,22576,22577,22578,22783,22783,22784,22785,22786,22786,23604,23604,22686,23053,23053,23054,23054,23055,23055,22992,23009,23010,23012,23013,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,S373P,S373P,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,R408S,P681H,P681H,S375F,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 17.2x-fold lower (95% CI: 0.6x-0.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22810,22810,22811,22812,22813,22813,22813,23009,23010,23012,23013" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484A,E484A,E484A,E484A" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario, using a retrospective matched case (age, gender and onset date) study of 6,312 Omicron cases vs 8,875 Delta, the adjusted risk of hospitalization or death was 54% lower (HR=0.46, 95%CI: 0.27, 0.77) among Omicron cases, after adjusting for vaccination statis and time since 2nd shot. The ratio for >60yo was 0.55 (95%CI: 0.28-1.06), and <60yo was 0.30 (95%CI: 0.16-0.57)." "" "" "" "Ulloa" "2021" "https://doi.org/10.1101/2021.12.24.21268382" "doi:10.1101/2021.12.24.21268382" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23009,23010,23012,23013" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,E484A,E484A,E484A,E484A" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection, evidenced by a reinfection hazard ratio of 2.39 (CI95: 1.88-3.11) relative to primary infection in the initial part of South Africa's 4th covid-19 wave (November 2021). In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. [minimal variant signature for Omicron (B.1.1.529) used based on H69del PCR dropout observed in November 2021 coincident with the rise of Omicron]" "" "" "" "Pulliam" "2021" "https://doi.org/10.1101/2021.11.11.21266068" "doi:10.1101/2021.11.11.21266068" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21987,21990,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23039,23040,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron (a.k.a. B.1.1.529) Spike pseudotyped VSV and Vero E6 cells has somewhat reduced neutralization (2.7x) vs wild type with monoclonal antibody Sotrovimab (a.k.a. VIR-7831). [delins at 214 omitted for syntax compatibility]" "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21987,21990,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23039,23040,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron breakthrough infection after 3-dose vaccination resulted in a further 3.5-fold and 2.9-fold increase of Omicron BA.1 and BA.2 neutralizing titers. Omicron BA.4/5 showed the highest neutralization resistance of all variants tested, resulting in low geometric mean neutralizing titers in plasma samples obtained after the second vaccine dose (NT50=72)." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron (B.1.1.529 [BA.1]) have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "All 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 729 NT50." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "All 10 individuals with 3 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 3319 NT50." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Omicron BA.1 variant is 1.0x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Omicron BA.1 has an IC50 fold change of 1.26x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Delta variant and was used to determine neutralizing antibodytitres. There was a 24.63x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 4.21x fold increase in antibody response pre-reinfection. There was a 39.27x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.1 has an IC50 fold change of 0.08x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Omicron variant and was used to determine neutralizing antibodytitres. There was a 114.84x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 6.61x fold increase in antibody response pre-reinfection. There was a 1194.9x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against B.1 variant and was used to determine neutralizing antibodytitres. There was a 6.76x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 2.06x fold increase in antibody response pre-reinfection. There was a 8.18x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Omicron BA.1 has an IC50 fold change of 0.38x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron B.1.1.529 (BA.1) neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 73 pM for binding to the Omicron B.1.1.529. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.1 has an IC50 fold change of 0.30x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigms’ ACE-2 variant LVE/STR chimera binds to SARS-2 Omicron variant B.1.1.529 spike protein trimer with high affinity. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.3 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.3 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22679,22679,22686,22992,21846,22992,22995,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075" "A67V,D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 4.2x-fold lower (95% CI: 0.15x-0.20x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22679,22679,22686,22992,21846,22992,22995,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075" "A67V,D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 6.2-fold lower (95% CI: 11.8x-14.3x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23048,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,24130,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22679,22679,22686,22992,21846,22992,22995,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075" "A67V,D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N856K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 28.7x-fold lower (95% CI: 0.03x-0.05) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23048,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,24130,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22679,22679,22686,22992,21846,22992,22995,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075" "A67V,D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N856K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 3.4-fold lower (95% CI: 3.2x-3.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23048,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,24130,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22679,22679,22686,22992,21846,22992,22995,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075" "A67V,D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N856K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "paired testing of vaccine sera against ancestral virus compared to Omicron BA.1 shows that 3-dose vaccine regimen provides over 50x fold increase in protection against Omicron(B.1.1.529 [BA.1]) compared to a 2-dose regimen." "" "" "" "Hao" "2022" "https://doi.org/10.1101/2022.08.12.22278720" "doi:10.1101/2022.08.12.22278720" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23048,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,24130,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22679,22679,22686,22992,21846,22992,22995,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075" "A67V,D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N856K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "4th antigenic exposure with Omicron (B.1.1.529 [BA.1])(n=29) infection increased variant specific plasma antibody and memory B cell responses as well as overall increased strain specific memory in individuals aged 22 –79 years, median age=33.5 years. Data collected 2.4 months after 3rd vaccination." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800" "D80N" "NC_045512.2:g.238G>A" "YP_009724390.1:p.Asp80Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800" "D80Y" "NC_045512.2:g.238G>T" "YP_009724390.1:p.Asp80Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This AA substitution outside the receptor binding domain in pseudotyped VSV promoted a 7.2% transduction rate in golden hamster cells, which was higher than that of human epithelial-like Huh-7 cells (6.6%)." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800,22188,22206,22597,22597,22599,23011,23012,23521,23521,23522,23524,23524,23525,23525,23604,23604" "D80Y,I210del,D215G,R346K,R346K,R346K,E484K,E484K,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Asp80Tyr,YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.VOI.V2 (first identified in Angola) reduced 8.0x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "One individual of 30 in the study, with HLA supertype HLA*A24:02, had a linear epitope that overlaps this variant of concern." "" "" "" "Redd" "2021" "https://doi.org/10.1101/2021.02.11.21251585" "doi:10.1101/2021.02.11.21251585" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolishes neutralizing activity of N-terminal-domain-directed mAb 4-19." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated that there is no free energy change (ddG) for this variant (i.e. same stability as wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In an Ontario long term care facility, cumulatively, weaker BNT162b2 vaccine stimulation, age/comorbidities, produced a ∼130-fold reduction in apparent neutralization titers in mean 88yo LTCH residents against Beta (B.1.351), relative to staff vaccinees against D614G wild type. 37.9% of 116 two-dose-mRNA-vaccinated residents had undetectable neutralizing antibodies to B.1.351. mRNA-1273 vaccinee sera displayed ~2 better neutralization than BNT162b2. [common defining B.1.351 mutations noted, as the manuscript does not provide details]" "" "" "" "Abe" "2021" "https://doi.org/10.1101/2021.08.06.21261721" "doi:10.1101/2021.08.06.21261721" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~10-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~3 fold without the deletion] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were significant, but ~500x weaker than in previously infected patients after first dose." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, 7 of 15 neutralized this B.1.351 pseudotype that includes the L242del, and only one had titers above 100. Only one of the 15 sera achieved 80% neutralization. [compare to 5 and 1 for pseudotype without the deletion]" "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.351 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 71%, Day 209 54%. Detectable antibodies against B.1.351 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 79%, Day 209 58%. Detectable antibodies against B.1.351 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 63%, Day 43 100%, Day 119 71%, Day 209 79%. Decreased neutralization on some assays was seen especially in those vaccinees tested that were 71+." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The B.1.351 variant constellation causes an ∼20-fold increase in affinity for ACE2 compared with Wuhan RBD, which may influence transmissibility." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Beta (B.1.351) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "humoral response durability" "" "" "In a prospective study of 107 hospitalized patients, decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7 and P.1 variants for at least 6 months (last of two samples taken) in patients previously hospitalized for COVID-19. A weaker protection was however observed for the B.1.351 variant." "" "" "" "Betton" "2020" "https://doi.org/10.1093/cid/ciab308" "doi:10.1093/cid/ciab308" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Beta (B.1.351) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Beta Molnupiravir (MK-4482) had ~1.75x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.351 defining mutations: Significant shift to infection in those without pre-existing conditions (79.6% vs 89% for non-VOC cases). Significant increase in hospitalization rate (19.3% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.3% vs 0.6% for non-VOC cases). PG: seems to be different notations around the LAL deletion, using the minimal shared definition to catch as many as possible." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Testing against B.1.351 the 20 most effective mAbs (19 anti-RBD, 1 anti-NTD) from a screen of 377 against wild type, 4 of 20 antibodies had >10-fold fall in neutralization titers, with most of these showing a complete knockout of activity. This is in line with the key roles of K417, E484, and N501, in particular E484, in antibody recognition of the ACE2 interaction surface of the RBD. Regeneron mAb cocktail: The neutralization of REGN10987 was unaffected by B.1.351, while REGN10933 was severely impaired (773-fold). AstraZeneca mAb cocktail: Neutralization by the AZ pair of antibodies was little affected on B.1.351 compared with Victoria." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v1 virus has reduced neutralization activity vs wild type: 34.5x (30 sera Pfizer median 9 days post 2nd dose) and 27.7x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination." "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination." "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Unlike wild type or B.1.1.7, B.1.351 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. PG: The virus used in these expriments has a non-typical deletion+sub in the 242 region." "" "" "" "Montagutelli" "2021" "https://doi.org/10.1101/2021.03.18.436013" "doi:10.1101/2021.03.18.436013" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Compared to Alpha (B.1.1.7) variant, odds of progressing to severe disease were 1.24-fold (95% CI: 1.11-1.39) higher for Beta. Odds of progressing to critical disease were 1.49-fold (95% CI: 1.13-1.97) higher. Odds of COVID-19 death were 1.57-fold (95% CI: 1.03-2.43) higher." "" "" "" "Abu-Raddad" "2021" "https://doi.org/10.1101/2021.08.02.21261465" "doi:10.1101/2021.08.02.21261465" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A two-dose regimen of (AstraZeneca) ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, vaccine efficacy against severe Covid-19 is undetermined." "" "" "" "Madhi" "2021" "https://doi.org/10.1101/2021.02.10.21251247" "doi:10.1101/2021.02.10.21251247" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine plasma neutralization of B.1.351-spike virus was nominally robust but lower (~3x) than other variants of concern." "" "" "" "Liu" "2021" "https://doi.org/10.1056/NEJMc2102017" "doi:10.1056/NEJMc2102017" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Beta (B.1.351) variant is 0.4x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Beta (B.1.351) has an IC50 fold change of 0.88x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Beta (B.1.351) has an IC50 fold change of 0.15x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v3 reduced 8.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x cleavage of S2 relative to WA1 (D614G) wildtype by Beta variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but A701V is downstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 34 convalescent cases 4–9 weeks following infection in June 2020, before the emergence of B.1.1.7, neutralization titers against B.1.351 were, on average, 13.3-fold reduced compared with an early Victoria sample (p < 0.0001). Significantly, 18 of 34 samples failed to reach 50% neutralization at a plasma dilution of 1:20, with a number showing a near total reduction of neutralization activity. In 13 convalescent cases 4–9 weeks following infection with B.1.1.7, neutralization titers against B.1.351 were, on average, 3.1-fold reduced compared with an early Victoria sample (p < 0.0001)." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using B.1.351 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~3-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~10 fold with L242del] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were signficiant, but >100x weaker than in previously infected patients after first dose." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, one third (5/15) of sera neutralized this B.1.351 pseudotype and only three had ID50 titers above 100. Only two of the 15 sera achieved 80% neutralization." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23664,23060,23061,23062,23062,23063,23063,23011,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Inoculation with the B.1.351 isolate resulted in lower clinical scores in 6 rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. Our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity." "" "" "" "Munster" "2021" "https://doi.org/10.1101/2021.05.07.443115" "doi:10.1101/2021.05.07.443115" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23664,23060,23061,23062,23062,23063,23063,23011,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission." "" "" "" "Yinda" "2021" "https://doi.org/10.1101/2021.05.05.442780" "doi:10.1101/2021.05.05.442780" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23664,23060,23061,23062,23062,23063,23063,23011,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission." "" "" "" "Yinda" "2021" "https://doi.org/10.1101/2021.05.05.442780" "doi:10.1101/2021.05.05.442780" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23664,23060,23061,23062,23062,23063,23063,23011,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "4 health care workers in the 20's and 30's with no underlying conditions and seropositivity or confirmed 2020 SARS-CoV-2 infections were confirmed to have B.1.351 infection during a Februrary 2021 hospital outbreak in Luxembourg. Symptoms were mostly mild on first infection, and milder on second infection." "" "" "" "Staub" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.18.2100423" "doi:10.2807/1560-7917.ES.2021.26.18.2100423" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.351 in 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "During an outbreak of SARS-CoV-2 501Y.V2 in a nursing home, all non-vaccinated residents (5/5) versus half of those fully vaccinated 2-5 weeks prior with BNT162b2 (13/26) were infected. Two of 13 vaccinated versus 4 of 5 non-vaccinated residents presented severe disease. BNT162b2 did not prevent the outbreak, but reduced transmission and disease severity. Among the 13 fully vaccinated residents who were infected, 2 (15.4%) presented with an asymptomatic disease, 9 (69.2%) developed mild to moderate symptoms, and 2 (15.4%) progressed to severe disease with fatal evolution secondary to acute respiratory distress syndrome (ARDS). There was no relationship between anti-S antibody levels at diagnosis and disease severity. Overall, the proportion of residents with severe disease in the non-vaccinated group (4/5) was higher than that in the vaccinated group (2/13). Only 1 vaccinated staff, but 10 unvaccinated were infected in the outbreak (no severe disease)." "" "" "" "Bailly" "2021" "https://doi.org/10.1093/cid/ciab446" "doi:10.1093/cid/ciab446" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.351 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0020 for moderate resistance." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer" "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer" "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.351 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. B.1.1.351 variant constellation ablates Class 3 N-terminal domain targeting antibodies COV2-2489 and COV2-2676 (the only two tested)." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In a Syrian hamster model, B.1.351 variant virus had >4x reduction in YRNT90 (measure of neutralization) using wild type convalescent sera. PG: Note that exact sequence for B.1.351 used was not disclosed." "" "" "" "Cochin" "2021" "https://doi.org/10.1101/2021.04.19.440435" "doi:10.1101/2021.04.19.440435" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.351 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the B.1.351 variants used, using the most popular as a stad in]" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v3 virus has reduced neutralization activity vs wild type: 42.4x (30 sera Pfizer median 9 days post 2nd dose) and 19.2x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype B.1.351 showed slight decrease in cell entry relative to wild type in 263T-ACE2 (kidney) cell line, and slight increase in Calu-3 (lung). Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.351 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "VSV pseudotype B.1.351 entry mediated by the S proteins of the B.1.351 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In one of eight cell lines tested (293T lung cells), a modest increase in cell entry was observed." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.351 lineage effectiveness was observed as 16.9% (95% CI [10.4,23.0]) against infection, and 0% against severe/critical/fatal disease (95% CI [0-19.0]). Two weeks or more after 2nd dose, effectiveness climbed to 75.0% [70.5,78.9] against infection, and 100% against severe/critical/fatal disease (95% CI [73.7,100])." "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Approximately 6-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "VSV pseudotype B.1.351 showed 7.86-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections)." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abrogates Bamlanivimab, Etesevimab, or their combined use neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine elicited antibodies neutralized virus with the B.1.351 spike protein had an average 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846" "T95I" "NC_045512.2:g.284C>T" "YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "65yo female with no severe Covid-19 risk factors tested positive 36 days after second dose of BNT162b2 (Pfizer) vaccine. Presented with fatigue, sinus congestion, and a headache developed; her symptoms plateaued and began to resolve six days later. [Mising genome coverage in regions of Spike covering clinically relevant mutations K417T, L452R, E484K, A701V, D796H, N501Y]" "" "" "" "Hacisuleyman" "2021" "https://doi.org/10.1056/NEJMoa2105000" "doi:10.1056/NEJMoa2105000" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22317,22319,22320,23399,23401,23401,23402,23403,23403" "T95I,D253G,D253G,D253G,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "B.1.526 (Iota) substantially increased IFR in older adults: by 46% (95% CI: 7.4 – 84%) among 45-64 year-olds, 82% (95% CI: 20 – 140%) among 65-74 year-olds, and 62% (95% CI: 45 – 80%) among 75+ during Nov 2020 – Apr 2021, compared to baseline IFR estimated for preexisting variants. [minimum clade defining mutations listed]" "" "" "" "Yang" "2021" "https://doi.org/10.1101/2021.08.04.21261596" "doi:10.1101/2021.08.04.21261596" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Sera from individuals who have been infected with Delta does not have strong neutralising activity against B.1.621" "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 69 test-positive were Mu. Two dose vaccine efficacy against Mu was 90.4% (73.9-96.5%), one dose VE was 45.8% (0.0-88.9%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from vaccinees [ChAdOx1 and BNT162b2 primarily used in UK] shows decreased ability to neutralize B.1.621 compared to first wave virus and Alpha, with a magnitude of change similar to Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against B.1.621." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D950N" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 12.4x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. [This is a greater reduction than Beta @ 8.2x]" "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D950N" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using live B.1.621 virus and a cytopathic effect-based assay, sera from 37 Pfizer/BioNTech BNT162b2 vaccinees collected 10-20 days post-booster showed significantly lower (95) but still ""robust"" neutralization than against ancestral B.1 virus (107)." "" "" "" "Messali" "2021" "https://doi.org/10.1002/jmv.27247" "doi:10.1002/jmv.27247" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D950N" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 7.6x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. [This is a greater reduction than Beta @ 6.3x]" "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22679,22679,23039,23039,23040,23521,23521,23522,23524,23524,23525,23525,24130,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,23060,23061,23062,23062,23063,23063,22879,22879,22881,22882,22882,22882,21618,23071,23071,23074,23074,23075,23075,22992,22995,23048,22810,22810,22811,22812,22813,22813,22813,22576,22577,22578,23604,23604,22686,23053,23053,23054,23054,23055,23055,22992,23009,23010,23012,23013,23399,23401,23401,23402,23403,23403" "T95I,S373P,S373P,Q493R,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,P681H,S375F,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 1.5x-fold lower (95% CI: 0.05x-0.07x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22679,22679,23039,23039,23040,23521,23521,23522,23524,23524,23525,23525,24130,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,23060,23061,23062,23062,23063,23063,22879,22879,22881,22882,22882,22882,21618,23071,23071,23074,23074,23075,23075,22992,22995,23048,22810,22810,22811,22812,22813,22813,22813,22576,22577,22578,23604,23604,22686,23053,23053,23054,23054,23055,23055,22992,23009,23010,23012,23013,23399,23401,23401,23402,23403,23403" "T95I,S373P,S373P,Q493R,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,P681H,S375F,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 4.4-fold lower (95% CI: 4.3x-4.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,23011,23012,23271,23399,23401,23401,23402,23403,23403,23604,23604,23948" "T95I,E484K,E484K,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D796H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp796His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "51yo female with no severe COVID-19 risk factors tested positive 19 days after second dose of mRNA-1273 (Moderna) vaccine. Presented with sore throat, congestion, and headache developed; the next day she lost her sense of smell. Symptoms resolved over a one week period. Serum obtained 4 days after symptom onset was tested for neutralization against wild-type virus, the E484K mutant, and the B.1.526 variant. It was equally effective against each. These data suggest that the antibody response recognized these variants but was nonetheless insufficient to prevent a breakthrough infection. The virus detected matched neither B.1.1.7 nor B.1.526 VOC strains in wide circulation in New York at the time of infection, though shared some mutations." "" "" "" "Hacisuleyman" "2021" "https://doi.org/10.1056/NEJMoa2105000" "doi:10.1056/NEJMoa2105000" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,23399,23401,23401,23402,23403,23403" "T95I,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21855" "S98F" "NC_045512.2:g.293C>T" "YP_009724390.1:p.Ser98Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly enhanced the transduction rate in raccoon dog (Nyctereutes procyonoides) kidney (62.4%) and Rickett’s big-footed bat (Myotis pilosus) kidney (45.0%) cell cultures compared to epithelial-like human Huh-7 cells (38.9%)." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21929" "A123S" "NC_045512.2:g.367G>T" "YP_009724390.1:p.Ala123Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected in passage with mAb COV2-2489 during alanine mutagenesis antibody mapping experiment." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21969" "C136Y" "NC_045512.2:g.407G>A" "YP_009724390.1:p.Cys136Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massively decreases N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21969" "C136Y" "NC_045512.2:g.407G>A" "YP_009724390.1:p.Cys136Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected twice in passage with mAb COV2-2489." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. [PG: This mutation is adjacent to a well known deletion, which may confound the significance of this variant]" "" "" "" "Lucaci" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "These variants dominate in mink infections in North America, sometime supplemented with F486L. The Y453F variant found in other jurisdictions in mink infections is notably absent in North America." "" "" "" "" "2021" "https://doi.org/10.1101/2021.03.18.21253734v3" "doi:10.1101/2021.03.18.21253734v3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~3.5x cleavage of S2 relative to WA1 (D614G) wildtype by Kappa (B.1.617.1) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~4.5x for closely related Delta B.1.617.2 also with P681R at the cleavage site)." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Kappa (B.1.617.1) shows mean 1.97x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617.1) showed a 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.1) showed a 1.12x increase in binding (KD) relative to D614G, but described as ""not significant"". [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617.1) showed a 1.79x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Average 2x neutralization efficiency decrease against sera from 26 Phase II trial Covaxin (BBV152) vaccine recipents. Very similar to B.1.1.7 (~2x) in the same study, and the neutralization from 17 sera of natural infections across B1 lineages." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.04.23.441101" "doi:10.1101/2021.04.23.441101" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cluster of B.1.617[.1] infections related to travel from India to USA, one patient with mild symptoms had received their second dose of Pfizer vaccine more than two weeks before the infection [i.e. vaccine breakthrough]." "" "" "" "Verghese" "2021" "https://doi.org/10.1128/JCM.00741-21" "doi:10.1128/JCM.00741-21" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Kappa (B.1.617.1) shows 5.71x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H,T95I" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Kappa (B.1.617.1) has an IC50 fold change of 0.68x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H,T95I" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Kappa (B.1.617.1) has an IC50 fold change of 2.3x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H,T95I" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Kappa (B.1.617.1) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H,T95I" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Kappa (B.1.617.1) has an IC50 fold change of 80.2x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Omicron BA.2 variant is 0.8x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Omicron BA.2 has an IC50 fold change of 0.08x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.2 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Omicron BA.2 has an IC50 fold change of 0.09x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.2 has an IC50 fold change of 0.04x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.2 has an IC50 fold change of 0.07x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.2 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21974" "D138Y" "NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.43 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21977" "P139S" "NC_045512.2:g.415C>T" "YP_009724390.1:p.Pro139Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected once in passage with mAb COV2-2676." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990" "Y145del,Y145del" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient." "" "" "" "McCarthy" "2021" "https://doi.org/10.1126/science.abf6950" "doi:10.1126/science.abf6950" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990" "Y145del,Y145del" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990,21993,21995,23011,23012,23399,23401,23401,23402,23403,23403" "Y145del,Y145del,H146del,H146del,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.His146del,YP_009724390.1:p.His146del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Normalized for particle number, on ACE2.293T cells showed that the B.1.618 spike protein was about as infective as D614G wild type." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21993,21995" "H146del,H146del" "NC_045512.2:g.436_438del,NC_045512.2:g.436_438del" "YP_009724390.1:p.His146del,YP_009724390.1:p.His146del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient." "" "" "" "McCarthy" "2021" "https://doi.org/10.1126/science.abf6950" "doi:10.1126/science.abf6950" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21997,21997,21998,21999,22000,22000,22001" "K147E,K147E,K147E,K147E,K147E,K147E,K147E" "" "YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21997,21997,21998,21999,22000,22000,22001" "K147E,K147E,K147E,K147E,K147E,K147E,K147E" "" "YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21998,21998" "H146Y,H146Y" "NC_045512.2:g.436C>T," "YP_009724390.1:p.His146Tyr,YP_009724390.1:p.His146Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in 4A8 monoclonal antibody EC50 (i.e. ablated recognition), but much milder effect on mAbs within antigenic supersite ""i""" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22001" "K147Q" "NC_045512.2:g.439A>C" "YP_009724390.1:p.Lys147Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22002" "K147T" "NC_045512.2:g.440A>C" "YP_009724390.1:p.Lys147Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22002" "K147T" "NC_045512.2:g.440A>C" "YP_009724390.1:p.Lys147Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massively decreases N terminal domain antigen recognition by supersite i mAbs S2M28, S2X28, S2X333, 4A8 (but not S2L28)." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22003" "K147N" "NC_045512.2:g.441A>T" "YP_009724390.1:p.Lys147Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22005" "N148S" "NC_045512.2:g.443A>G" "YP_009724390.1:p.Asn148Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong positive selection (up to 72% of supernatant sequences) under six rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22010" "K150E" "NC_045512.2:g.448A>G" "YP_009724390.1:p.Lys150Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong positive selection (up to 40% of supernatant sequences) under three rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22010" "K150E" "NC_045512.2:g.448A>G" "YP_009724390.1:p.Lys150Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22011" "K150R" "NC_045512.2:g.449A>G" "YP_009724390.1:p.Lys150Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 18% of supernatant sequences) under two rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22011" "K150T" "NC_045512.2:g.449A>C" "YP_009724390.1:p.Lys150Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 22% of supernatant sequences) after COV47 convalescent plasma assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22016,22016,22016" "W152R,W152R,W152R" ",NC_045512.2:g.454T>A,NC_045512.2:g.454T>C" "YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For NTD-binding neutralizing antibody ADI-56479 this mutation causes a 1000x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22016,22016,22016" "W152R,W152R,W152R" ",NC_045512.2:g.454T>A,NC_045512.2:g.454T>C" "YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22018" "W152C" "NC_045512.2:g.456G>T" "YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Pseudoviruses carrying the W152C mutation demonstrated small increases in cell entry compared to D614G alone in 293T cells and human airway organoids." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22018" "W152C" "NC_045512.2:g.456G>T" "YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The W152C mutation reduced recognition of six NTD neutralizing mAbs, including a complete loss of binding for two of them, with a complementary pattern to that observed for S13I (also found in lineage B.1.427/B.1.429) out of 11 neutralizing mAbs evaluated." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022" "E154K" "NC_045512.2:g.460G>A" "YP_009724390.1:p.Glu154Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604" "E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abrogates Bamlanivimab neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Significant decrease in combined Etesevimab+Bamlanivimab neutralization except at the highest concentration measured. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604" "E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pfizer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~3x (compared to ~11x for B.1.351). [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604" "E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Approximately 2-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604" "E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In two of eight cell lines tested (Caco-2 intenstinal and Calu-3 lung), a modest increase in cell entry was observed. This increase was not observed in a Calu-3 cell line with overexpressed ACE2. [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22028,22034" "R158G,R158G" "NC_045512.2:g.467_472del,NC_045512.2:g.472A>G" "YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22033,23011,23012,23604,23604" "F157L,E484K,E484K,P681R,P681R" "" "YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.23.1-v2 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22033,23604,23604" "F157L,P681R,P681R" "NC_045512.2:g.471C>A,NC_045512.2:g.2042C>G," "YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.23.1-v1 reduced 1.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22036" "R158S" "NC_045512.2:g.474A>T" "YP_009724390.1:p.Arg158Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected three times in passage with mAb COV2-2489." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:03." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DPB1*04:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*07:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type C*07:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*16:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22107,22111" "Q183H,Q183H" "NC_045512.2:g.549G>T,NC_045512.2:g.549G>T" "YP_009724390.1:p.Gln183His,YP_009724390.1:p.Gln183His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome" "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132" "R190S" "NC_045512.2:g.570G>T" "YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.69 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132,22600,22600,22907,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in B.1.640.2 variant was ~1000x folds more significant in 8 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132,22600,22600,22907,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1.640.2 variant was ~5.6x folds more significant in 9 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22188,23399,23401,23401,23402,23403,23403" "I210del,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "A 42yo Iranian male was reinfected with B.1.36 lineage virus 128 days after infection with genetically distinct B.1.36 virus, with negative PCR tests in between. In the first instance patient presented with cough, headache, severe diarrhea. In the second instance symptoms were more severe: body pain, shortness of breath, headache and anosmia. Anti-SARS-CoV-2 IgG and IgM tests were negative after both episodes. [Non-seroconversion may be associated with elevated risk of re-infection] [I210del is a homoplasy that has appeared in several disparate parts of the global phylogenetic tree, including A and B lineages, primarily in LMICs]" "" "" "" "Salehi-Vaziri" "2021" "https://doi.org/10.1016/j.virusres.2021.198421" "doi:10.1016/j.virusres.2021.198421" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:02." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.98 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:01." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*13:02." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227" "A222V,A222V" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227,23399,23401,23401,23402,23403,23403" "A222V,A222V,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3). Both cases were mild. Second case also includes N:p.A220V" "" "" "" "Brehm" "2021" "https://doi.org/10.3390/v13040661" "doi:10.3390/v13040661" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227,23399,23401,23401,23402,23403,23403" "A222V,A222V,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "humoral response durability" "" "" "27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3), i.e. with a 9 month interval. Both cases were mild. No significant differences in the neutralizing capacity of the two lineages were observed in 4 sera taken (1 pre-reinfection, three post-reinfection). Neutralizing antibody titres (IC50) before and immediately after re-infection were <300 against both strains, and jumped >7x upon re-infection. Viral titres were also higher in the second case. Second case also includes N:p.A220V" "" "" "" "Brehm" "2021" "https://doi.org/10.3390/v13040661" "doi:10.3390/v13040661" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22293" "L244S" "NC_045512.2:g.731T>C" "YP_009724390.1:p.Leu244Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22301" "S247R" "NC_045512.2:g.739A>C" "YP_009724390.1:p.Ser247Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22304" "Y248H" "NC_045512.2:g.742T>C" "YP_009724390.1:p.Tyr248His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22314" "P251L" "NC_045512.2:g.752C>T" "YP_009724390.1:p.Pro251Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317" "G252D" "NC_045512.2:g.755G>A" "YP_009724390.1:p.Gly252Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317,22319,22320" "D253G,D253G,D253G" "NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317,22319,22320" "D253G,D253G,D253G" "NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22319" "D253Y" "NC_045512.2:g.757G>T" "YP_009724390.1:p.Asp253Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22323" "S254F" "NC_045512.2:g.761C>T" "YP_009724390.1:p.Ser254Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22323" "S254Y" "NC_045512.2:g.761C>A" "YP_009724390.1:p.Ser254Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22326" "S255F" "NC_045512.2:g.764C>T" "YP_009724390.1:p.Ser255Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22328,22329,22331" "G257S,G257S,G257S" "NC_045512.2:g.769G>A,NC_045512.2:g.769G>A,NC_045512.2:g.769G>A" "YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334" "W258R" "NC_045512.2:g.772T>C" "YP_009724390.1:p.Trp258Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334" "W258R" "NC_045512.2:g.772T>C" "YP_009724390.1:p.Trp258Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334,22879,22879,22881,22882,22882,22882,22904,22910,23011,23012" "W258R,N440K,N440K,N440K,N440K,N440K,N440K,N450D,N450D,E484K,E484K" "" "YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22340" "A260T" "NC_045512.2:g.778G>A" "YP_009724390.1:p.Ala260Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22344" "G261D" "NC_045512.2:g.782G>A" "YP_009724390.1:p.Gly261Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Multiple mink but no humans on one farm in Denmark, potential adaptation." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22377,22377" "P272L,P272L" ",NC_045512.2:g.815C>T" "YP_009724390.1:p.Pro272Leu,YP_009724390.1:p.Pro272Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*08:01." "" "" "" "Dolton" "2021" "https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf" "doi:10.1101/2021.06.21.21259010v2.full.pdf" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22377,22377" "P272L,P272L" ",NC_045512.2:g.815C>T" "YP_009724390.1:p.Pro272Leu,YP_009724390.1:p.Pro272Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*02:01." "" "" "" "Dolton" "2021" "https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf" "doi:10.1101/2021.06.21.21259010v2.full.pdf" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22573,22574,22576,22577" "G339H,G339H,G339H,G339H" "" "YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22573,22574,22576,22577,22595,22596,22597,22597,22599,22599,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22895,22939,22939,22942,22942,22942,22992,23009,23010,23012,23013,23017,23018,23027,23029,23029,23030,23031,23031,23053,23053,23054,23054,23055,23055,22992,22995,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075" "G339H,G339H,G339H,G339H,R346T,R346T,R346T,R346T,R346T,R346T,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,V445P,N460K,N460K,N460K,N460K,N460K,S477N,E484A,E484A,E484A,E484A,F486P,F486P,F490S,F490S,F490S,F490S,F490S,F490S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,T478K,T478K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Val445Pro,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The hACE2-binding affinity of XBB.1.5 RBD has a dissociation constant KD of 3.4 nM, where S486P is the distinguishing Spike mutation vs parent XBB.1 RBD with a much weaker KD (19 nM), as measured by surface plasmon resonance (SPR) assays." "" "" "" "Yue" "2023" "https://doi.org/10.1101/2023.01.03.522427" "doi:10.1101/2023.01.03.522427" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 1.2x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.3 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22577" "G339N" "" "YP_009724390.1:p.Gly339Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.11 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22583" "V341I" "NC_045512.2:g.1021G>A" "YP_009724390.1:p.Val341Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22597,22599,22599" "R346T,R346T,R346T,R346T,R346T,R346T" "" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22597,22599,22599" "R346T,R346T,R346T,R346T,R346T,R346T" "" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22597,22599" "R346K,R346K,R346K" ",NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22597,22599" "R346K,R346K,R346K" ",NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 53% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22597,22599" "R346K,R346K,R346K" ",NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation, which has emerged in some Omicron sequences, has a 0.7x reduction in neutralization activity with Sotrovimab in a VSV model on Vero E6 cells. [Omicron sequences with R346K may very well have a non-additive neutralization rather than 2.7x+0.7x = 3.4x]" "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346I,R346I" "NC_045512.2:g.1037G>T,NC_045512.2:g.1037G>T" "YP_009724390.1:p.Arg346Ile,YP_009724390.1:p.Arg346Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Provides ~80% escape from mAb COV2-2130, even though its appearance in culture is formed without selective mAb pressure." "" "" "" "Dong" "2021" "https://doi.org/10.1101/2021.01.27.428529" "doi:10.1101/2021.01.27.428529" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22598" "R346E" "" "YP_009724390.1:p.Arg346Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.08 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 2/3 antibody C603." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 30% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 2/3 antibody C603." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22622" "N354D" "NC_045512.2:g.1060A>G" "YP_009724390.1:p.Asn354Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.13 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22623" "N354S" "" "YP_009724390.1:p.Asn354Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.17 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22624" "N354K" "NC_045512.2:g.1062C>A" "YP_009724390.1:p.Asn354Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22627,22627,22629" "K356T,K356T,K356T" ",NC_045512.2:g.1067A>C,NC_045512.2:g.1067A>C" "YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.14 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22629" "K356R" "NC_045512.2:g.1067A>G" "YP_009724390.1:p.Lys356Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22632" "R357K" "NC_045512.2:g.1070G>A" "YP_009724390.1:p.Arg357Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.18 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.72 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as ""stabilizing"" since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as ""stabilizing"" since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22661" "V367I" "NC_045512.2:g.1099G>A" "YP_009724390.1:p.Val367Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22679,22679" "S373P,S373P" "NC_045512.2:g.1117T>C," "YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Reduce affinity for mildly cross-reactive CR3022 (2003 pandemic SARS monoclonal antibody cross-reactive to SARS-CoV-2)" "" "" "" "Long" "2020" "https://doi.org/10.1128/mBio.02707-20" "doi:10.1128/mBio.02707-20" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22679,22679,23009,23010,23012,23013" "S373P,S373P,E484A,E484A,E484A,E484A" "" "YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "On December 7, 2021 the estimate of Omicron effective reproduction rate (Rt) is 3.12 [presumably R0 is higher], compared to 1.12 for the dominant Delta VOC at that time. [shorthand of variant list shraed by all contemporary BA lineage used here]" "" "" "" "" "2021" "https://doi.org/10.47326/ocsat.dashboard.2021.1.0" "doi:10.47326/ocsat.dashboard.2021.1.0" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22686" "S375F" "NC_045512.2:g.1124C>T" "YP_009724390.1:p.Ser375Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch." "" "" "" "Lucaci" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22696" "K378N" "NC_045512.2:g.1134G>T" "YP_009724390.1:p.Lys378Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for mildly neutralizing COV2-2677 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23401,23402,23403,23403" "P384L,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23401,23402,23403,23403" "P384L,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23401,23402,23403,23403" "P384L,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22745" "V395I" "NC_045512.2:g.1183G>A" "YP_009724390.1:p.Val395Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22766" "I402V" "NC_045512.2:g.1204A>G" "YP_009724390.1:p.Ile402Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22783,22783,22784,22785,22786,22786" "R408S,R408S,R408S,R408S,R408S,R408S" ",NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C" "YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22783,22783,22784,22785,22786,22786,23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "R408S,R408S,R408S,R408S,R408S,R408S,E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a study of 481 vaccinees going from lowest to highest infection rate, 2 doses of CoronaVac and 1 dose of BNT162b2 had the lowest infection rate at 6.3%, then it was 3 doses of BNT162b2 having a infection rate of 16.6%. 2 and 3 doses of CoronaVac had 48.6% and 20.6% infection rate respectively. 2 doses of BNT162b2 has the highest infection rate at 49.2%." "" "" "" "Zhou" "2022" "https://doi.org/10.1101/2022.05.09.491254" "doi:10.1101/2022.05.09.491254" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22784" "R408G" "" "YP_009724390.1:p.Arg408Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.09 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection, Two-tailed Wilcoxon matched-pairs signed-rank test shows mild resistance P=0.0361." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C682, and to a lesser extent C614 and C660" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs)" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs)" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates binding by RBD-directed mAbs CB6 and 910-30 (targeting the inner side of the RBD). Pseudotyped virus model impairs binding by RBD-directed mAbs 4-20 and REGN10933." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~6x binding against this isolated mutation. Estesevimab lost ~100x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 7.5 fold decrease in KD value for antibody binding of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 36.9 fold decrease in KD value for antibody binding of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "1.1 fold drop in IC50 of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 1.5 fold decrease in KD value of antibody binding of ACE2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The K417N mutation decreased the affinity ~4 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 3-fold decrease in affinity compared to wild-type RBD on the cell surface (Kd = 145.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.86 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against IgG1 monoclonal antibody ab1." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Moderna vaccinee sera, 2.7x reduction in neutralization, and 6.4 for the full B.1.351 Spike mutation complement, but despite the observed decreases, titers in human vaccinee sera against the B.1.351 variant remained at clinically significant level of ~1/300." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.01.25.427948" "doi:10.1101/2021.01.25.427948" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.351 and P.1 samples showed average Ct cycle threshold of 22.2 vs 23 for wildtype (i.e. ~60% higher viral load) comparing 3360 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26)." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "27% of 44 early pandemic exposure convalescent plasma/sera lose all activity against a RBD triple mutant pseudovirus (RBD mutatants of the 501Y.V2 ""South African"" lineage), while only 23% retained high titres" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from B.1.351." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26)." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibodies ab8 and IgG1 ab1. Complete loss for the same antibodies was also observed against S1 pseudotyped and full Spike protein trimers with both B.1.351 and P.1 lineage variants, with slight binding signal for P.1 against IgG1 at the highest concentration tested (1uM). Complete loss of neutralization by these two antibodies was also observed." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of the B.1.351 RBD variants for ACE2 increased by 3.7 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.4-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.351 key variants lentivirus. Compare to 8.8-fold reduction against cultured B.1.351 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This combination showed ~3x increase binding to ACE2 vs wild type, about half that of the B.1.1.7 lineage, suggesting that the K417N mutation is slightly detrimental to ACE2 binding, probably as a result of disrupting the salt bridge formed with ACE2 residue D30" "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant of key B.1.351 lineage mutations showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolished neutralization by mAbs CQ026 and CQ038, greatly diminished neutralization by CQ012 and CQ046." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) with enrollment June 24 and November 9, 2020 from ~2000 HIV-negative 18-64 year olds (1:1 placebo to treatment), incidence of serious adverse events 14 or more days post- 2nd dose was balanced between the vaccine and placebo groups. A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed 3.5x reduction in neutralization (ID50) for B.1.351 RBD pseudotype HIB-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a similar 3.2x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "36,590 variant-specific RT-PCR tests were performed on samples collected between April 12 and May 7, 2021 in France to compare variant spread. Compared to January to March 2021, B.1.351 variant had a significant transmission advantage over B.1.1.7 in some regions (15.1 to 16.1% in Île-de-France and 16.1 to 18.8% in Hauts-de-France). This shift in transmission advantage is consistent with the immune evasion abilities of B.1.351 and the high levels of immunization in these regions." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.05.12.21257130" "doi:10.1101/2021.05.12.21257130" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure." "" "" "" "Pearson" "2021" "https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure." "" "" "" "Pearson" "2021" "https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Average ~10-fold reduction in neutralization efficacy in convalescent sera of 16 health workers infected in Spring 2020." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 2 (B.1.351) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23041,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Lung viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~2266x fold drop in the R3P1-E4 antibody in comparison to the IgG control." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23041,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "100% of the 5 8‑month‑old male R3P1-E4 antibody treated mice suvived 14 days after infection while only 60% the control group mice survived 5 days post infection." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23041,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trachea viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~750x fold drop in the R3P1-E4 antibody in comparison to the IgG control." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (no synergy as level approx. that of N501Y alone)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~5x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied]" "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22811" "K417H" "" "YP_009724390.1:p.Lys417His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22811" "K417D" "" "YP_009724390.1:p.Lys417Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Most and moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Mildly effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22811" "K417D" "" "YP_009724390.1:p.Lys417Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Most and moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Mildly effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22811" "K417H" "" "YP_009724390.1:p.Lys417His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22811" "K417D" "" "YP_009724390.1:p.Lys417Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, but moderate decrease in ACE2 binding affinity" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417I" "" "YP_009724390.1:p.Lys417Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417I" "" "YP_009724390.1:p.Lys417Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.39 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 antibody C682" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 57.1 fold decrease in KD value for antibody binding of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 1.1 fold decrease in KD value of antibody binding of ACE2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.25 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~16x binding against this isolated mutation. Estesevimab lost ~16x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "2.6 fold increase in IC50 of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 2.9 fold decrease in KD value for antibody binding of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The K417T mutation decreased the affinity ~2 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.64 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812,23011,23012,23060,23061,23062,23062,23063,23063" "K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of the P.1 RBD variants for ACE2 increased by 5.3 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812,23011,23012,23060,23061,23062,23062,23063,23063" "K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from P.1." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The KD for the pseudotyped P.1-ACE2 interaction is 4.8 nM, showing that binding to P.1 is essentially indistinguishable from B.1.351 (4.0 nM), which binds with ~19x greater affinity that wild type." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22851" "T430I" "NC_045512.2:g.1289C>T" "YP_009724390.1:p.Thr430Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22865" "A435S" "NC_045512.2:g.1303G>T" "YP_009724390.1:p.Ala435Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb H014 (on D614G background)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The N440K variant produced ten times higher infectious viral titers than a prevalent A2a strain, and over 1000 folds higher titers than a much less prevalent A3i strain prototype in Caco2 cells. Interestingly, A3i strain showed the highest viral RNA levels, but the lowest infectious titers in the culture supernatants, indicating the absence of correlation between the RNA content and the infectivity of the sample." "" "" "" "Tandel" "2021" "https://doi.org/10.1101/2021.04.30.441434" "doi:10.1101/2021.04.30.441434" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 0.7x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 3 antibody C669 mildly selected for the emergence of the N440K mutation in vitro (in contrast to N440H which caused mild escape in Class 1/2 mAb C653)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "N501Y substitution decreased the neutralizing and binding activities of CB6 and increased that of BD-23" "" "" "" "Cheng" "2021" "https://doi.org/10.1186/s12985-021-01554-8" "doi:10.1186/s12985-021-01554-8" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 45% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, eliminated in subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882,23399,23401,23401,23402,23403,23403" "N440K,N440K,N440K,N440K,N440K,N440K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "A 47yo Indian male was reinfected with B.1.36 lineage virus in September 2020 after infection with genetically distinct B.1.36 virus in July, with negative PCR tests in between. While the forst episode was asymptomatic, the second included fever, cough, and malaise. The second case additionally contained stopgain ORF3a:E261*" "" "" "" "Rani" "2021" "https://doi.org/10.1002/jmv.26997" "doi:10.1002/jmv.26997" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444R" "NC_045512.2:g.1331A>G" "YP_009724390.1:p.Lys444Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Identified in 6/20 replicates of recombinant VSV growth in the presence of mAb COV2-2130." "" "" "" "Dong" "2021" "https://doi.org/10.1101/2021.01.27.428529" "doi:10.1101/2021.01.27.428529" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444R" "NC_045512.2:g.1331A>G" "YP_009724390.1:p.Lys444Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 20% of supernatant sequences) under two rounds of COV-NY convalescent plasma passage, eliminated in rounds three and four" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893,22893" "K444T,K444T" ",NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr,YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893,22893" "K444T,K444T" ",NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr,YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Results in 3.7-fold drop in neutralization potency for COVA2-29, which is a cluster I RBD141 specific antibody." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893,22893" "K444T,K444T" ",NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr,YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Improvement in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolishes binding efficiency vs wild type for mAb REGN10933." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-01 and moderately resistant to 2H04 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 14% of supernatant sequences) after COV-NY convalescent plasma assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22895" "V445P" "" "YP_009724390.1:p.Val445Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.05 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22896" "V445A" "NC_045512.2:g.1334T>C" "YP_009724390.1:p.Val445Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 41% appearance in 2 passages against Regeneron monoclonal antibody RGN10987 @ 10ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed a ~4x drop in sensitivity." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 1 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-02, SARS2-32 and SARS2-35 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Decrease in neutralization capability of all 4 convalescent sera tested (1 ablated)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2499 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations), triple replicates. Against a broader panel of 16 convalescent plasma (no replicates), reductions in neutralization are considerably less dramatic in pattern, and sometime neutralization increases." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 4 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 95% appearance in 2 passages against Regeneron monoclonal antibody RGN10934 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-07 nd moderately resistant to SARS2-16 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Most effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910,23011,23012,23039,23039,23040,23373,25045,25046,25046" "N450D,N450D,E484K,E484K,Q493R,Q493R,Q493R,T604I,P1162S,P1162S,P1162S" "" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Thr604Ile,YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22905" "N448S" "NC_045512.2:g.1343A>G" "YP_009724390.1:p.Asn448Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22907" "Y449H" "NC_045512.2:g.1345T>C" "YP_009724390.1:p.Tyr449His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22907" "Y449N" "NC_045512.2:g.1345T>A" "YP_009724390.1:p.Tyr449Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912,22912,22916" "L452M,L452M,L452M" ",NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A" "YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912,22912,22916" "L452M,L452M,L452M" ",NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A" "YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We observed increased entry by pseudoviruses carrying the L452R mutation compared to D614G alone, with a 6.7 to 22.5-fold increase in 293T cells and a 5.8 to 14.7-fold increase in human airway organoids." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 3 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Increased stability of RBD expression in yeast, suggesting increased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-02 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.32 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~5x binding against this isolated mutation. Cligavimab lost ~4x binding against this isolated mutation. Regdanvimab lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs X593 and P2B-2F6" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02." "" "" "" "Motozono" "2021" "https://doi.org/10.1016/j.chom.2021.06.006" "doi:10.1016/j.chom.2021.06.006" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Ablation of neutralization capability of 3 of 4 convalescent sera tested, the other is significantly hindered." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "L452R derivative virus did not induce IFN-gamma expression even at the highest concentration tested (10 nM) in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456)." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~1.7-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2/3 antibody C628 and class 2 antibody C643 selected for the emergence of the L452R mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Observed ~2x decrease on average in neutralization efficacy in convalescent sera of 16 health workers." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.67 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "10 of 14 RBD-specific mAbs that showed at least 10-fold reduced neutralization of B.1.427/B.1.429 variant pseudotype (S13I, W152C, and L452R) were also found to poorly bind to just a L452R RBD mutant, demonstrating a role for this mutation as an escape mechanism for certain RBD-targeting mAbs." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. L452R conferred about a two-fold reduction in neutralisation by vaccine sera, but was not statistically significant with this sample size." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. [listed as L454R in Figure, but L452R in text, also text suggests not statistically significant, but error bars say otherwise in Figure 4]" "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23011,23012" "L452R,L452R,L452R,L452R,L452R,L452R,E484K,E484K" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant combination shows a ~4-5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, same as L452R alone." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23011,23012,23604,23604" "L452R,L452R,L452R,L452R,L452R,L452R,E484K,E484K,P681R,P681R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant combination shows a ~3x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, significantly less of a decrease than any B.1.617 lineage variants alone, suggesting a synergistic effect on cell entry while maintaining known immunity esacpe mutants." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484Q had a ~5x drop in neutralization (vs ~10x for E484K). When E484Q and L452R were combined, the fold change was significant, but similar to that of L452R alone (~2x), suggesting no evidence for an additive effect [perhaps even E484Q effect dilution]." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x infectivity advantage to the spike particles [less than L452R or E484Q alone working with the delins]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Pseudotyped viruses for B.1.617 was 2.3-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. [details on the convalescent patient sera collection are not abundantly clear in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2.5x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x drop in neutralization (NT50) [working with the delins, less than just L452R but more than just E484Q]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617) showed a 1.30x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.18x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The combination caused a 3-fold increase in infectivity relative to D614G wild type. [compare to 3.5x for L452R alone]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617) showed a 1.85x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617) showed a 1.22x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23604,23604" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,P681R,P681R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In 9 infected hamsters each for B.1 and B.1.617.1, no significant change in viral load or subgenomic RNA levels were detected." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.05.05.442760" "doi:10.1101/2021.05.05.442760" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23604,23604" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,P681R,P681R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Gross examination of 3+3 hamster lung specimens showed pronounced congestion and hemorrhages on days 5 and 7 post-infection in the case of the B.1.617.1 as compared with the B.1. The lung lesions with the B.1 variant were minimal to mild whereas with B.1.617.1 they were moderate. For B.1 pneumonic changes were minimal to mild (inflammatory cell infiltration, focal consolidation and mild congestion). The pronounced changes (moderate to severe) with mononuclear infiltration in the alveolar interstitial space, interstitial septal thickening, consolidation and pneumocyte hyperplasia were observed with B.1.617.1 variant consistently." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.05.05.442760" "doi:10.1101/2021.05.05.442760" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23604,23604,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,P681R,P681R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Normalized for particle number, on ACE2.293T cells showed that the B.1.617 spike protein was >2-fold increase in infectivity relative to D614G wild type." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23060,23061,23062,23062,23063,23063" "L452R,L452R,L452R,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of these B.1.417/B.1.429 defining variants in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The L452R mutation increased the infectivity more than two-fold in these conditions." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this RBD mutation conferred a 2.36x drop in neutralization (NT50)." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~2x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 583 test-positive were Epsilon. Two dose vaccine efficacy against Epsilon was 97.6 (90.2-99.4%), one dose VE was 76.3 (48.1-89.1%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 7.42x drop in neutralization (NT50) [mostly from 3 of the sera]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916" "L452W,L452W" "" "YP_009724390.1:p.Leu452Trp,YP_009724390.1:p.Leu452Trp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917" "L452Q" "NC_045512.2:g.1355T>A" "YP_009724390.1:p.Leu452Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917" "L452Q" "NC_045512.2:g.1355T>A" "YP_009724390.1:p.Leu452Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.27 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403" "L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.048x fold change in IC50 in C.37 Lambda" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403" "L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.038x fold change in IC50 in C.37 Lambda" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403" "L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 3.4x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403" "L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 1.7x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.25 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Casirivimab lost >50x binding against this mutation." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.celrep.2021.109017" "doi:10.1016/j.celrep.2021.109017" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "" "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed in 4 separate mink farms in Denmark, and Y453F is circulating relatively widely in humans." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02." "" "" "" "Motozono" "2021" "https://doi.org/10.1016/j.chom.2021.06.006" "doi:10.1016/j.chom.2021.06.006" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "VSV pseudotyped with Y453F reduced inhibition by most of the 13 potent convalescent serum/plasma samples tested, albeit with variable efficiency (median increase of serum/plasma titer required for 50% neutralization [NT50] = 1.62x, range = 1.02x to 3.43x), indicating that this RBD mutation may compromise SARS-CoV-2 control by preexisting neutralizing antibody responses." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.celrep.2021.109017" "doi:10.1016/j.celrep.2021.109017" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~12x binding against this double mutation. Casirivimab lost ~64x binding against this double mutation. Cligavimab lost ~6x binding against this double mutation. Estesevimab lost ~10x binding against this double mutation. Imdevimab lost ~5x binding against this double mutation. Regdanvimab lost ~8x binding against this double mutation. Sotrovimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "10-fold reduction in binding efficiency vs wild type for MAb REGN10933." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "The induction level of IFN-gamma expression by the Y453F derivative in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456) was significantly lower." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "Y453F,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "The so-called ""delta F"" variant combination previously observed in mink spillover events also emerged in a lymphoma patient (non-Hodgkin diffuse B-cell lymphoma IV stage B) with a long-term COVID-19 infection (4 months) where 18 de novo mutation occureed overall. Patient was taking rituximab, the B-cell-depleting agent, and had no detectable neutralizing antibody response." "" "" "" "Bazykin" "2021" "https://virological.org/t/emergence-of-y453f-and-69-70hv-mutations-in-a-lymphoma-patient-with-long-term-covid-19/580" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22924,22924,22925,22926" "L455S,L455S,L455S,L455S" ",NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C" "YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.45 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22925" "L455A" "" "YP_009724390.1:p.Leu455Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.58 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22926,22927,22927,22928,22930,22930" "F456L,F456L,F456L,F456L,F456L,F456L" "NC_045512.2:g.1366T>C,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>A,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>G,NC_045512.2:g.1368T>A" "YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This double substitution reduces neutralization by RBD-specific mAbs from different clusters, specifically, the cluster I mAb COVA2-29, cluster III mAb COVA2-07 and cluster VI mAb COVA1-12. For COVA1-12 all neutralization activity is abolished, while COVA2-07 activity is just below the level required to calculate an IC50 value." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Moderate in vitro selection against class 1 (Spike 'up' conformation) antibodies C683 and C664. Unclassified antibody C666 selected for the emergence of the F456V mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22936" "K458N" "NC_045512.2:g.1374G>T" "YP_009724390.1:p.Lys458Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.09 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460Y" "NC_045512.2:g.1378A>T" "YP_009724390.1:p.Asn460Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mild escape mutant emergent for class 1 antibody C613 in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22941" "N460I" "NC_045512.2:g.1379A>T" "YP_009724390.1:p.Asn460Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22941" "N460S" "NC_045512.2:g.1379A>G" "YP_009724390.1:p.Asn460Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22964" "I468V" "NC_045512.2:g.1402A>G" "YP_009724390.1:p.Ile468Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22964" "I468V" "NC_045512.2:g.1402A>G" "YP_009724390.1:p.Ile468Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22976" "I472V" "NC_045512.2:g.1414A>G" "YP_009724390.1:p.Ile472Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb X593 (on D614G background)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22976" "I472V" "NC_045512.2:g.1414A>G" "YP_009724390.1:p.Ile472Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~50x binding against this isolated mutation. Estesevimab lost ~8x binding against this isolated mutation. Sotrovimab lost ~30x binding against this isolated mutation. Tixagevimab lost ~15x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some class 1 (Spike 'up' conformation) antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C102, C105 and C144 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding, with increasing proportion in subsequent rounds." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 2.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows some resistence across all antibodies tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "While S477N itself is highly resistent to a broad range of monoclonal antibodies, combined with S514F high neutralization is restricted to only three antibodies in a broad screen." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of mild positive and negative changes in neutralization capability of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), 10 show low neutralization." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.22 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 host variant dependency" "" "" "This mutation's measured interaction affinity with ACE2:p.S19P (0.03% minor allele frequency, found almost exclusively in African/African-Americans in the GnomAD database) was significantly lower than the predicted value, indicating that these mutations were not independent. This is consistent with the fact that the ACE2 residue S19 is adjacent to RBD residue S477 in the contact interface." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility." "" "" "" "Singh" "2021" "https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility." "" "" "" "Singh" "2021" "https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-07, SARS2-16 and SARS2-19 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-07 and SARS2-16 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 11 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,22995,23042" "T478K,T478K,S494P" "NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1480T>C" "YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Combination of RBD mutations appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome complicated by diffuse alveolar hemorrhage, who was receiving anticoagulation therapy, glucocorticoids, cyclophosphamide, and intermittent rituximab and eculizumab." "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23011,23012" "S477N,E484K,E484K" "" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~10x binding against this double mutation. Tixagevimab lost ~16x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23401,23402,23403,23403" "S477N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "11 cases of re-infection with the ""Marseille-4"" variant found within 1028 positive tests, where all of the earlier infections were from different strains. This lineage is also characterized by N:p.M234I;A376T" "" "" "" "Fournier" "2021" "https://doi.org/10.1016/j.ijid.2021.03.068" "doi:10.1016/j.ijid.2021.03.068" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23401,23402,23403,23403" "S477N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was neutralized slightly less than D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23401,23402,23403,23403" "S477N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23401,23402,23403,23403" "S477N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Compared to the clade 20A strains that predominated during phase 1 between March and May 2020, the Marseille-4 variant (characterized by this mutation plus N:p.M234I;A376T) was associated with a lower frequency of cough, rhinitis, and olfactory and gustatory disorders. By contrast, hypoxemia was more frequent in patients infected with the Marseille-4 variant." "" "" "" "Fournier" "2021" "https://doi.org/10.1016/j.ijid.2021.03.068" "doi:10.1016/j.ijid.2021.03.068" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23003" "N481Y" "NC_045512.2:g.1441A>T" "YP_009724390.1:p.Asn481Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Minor variant in initial round of in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009" "V483L" "NC_045512.2:g.1447G>C" "YP_009724390.1:p.Val483Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, 1B07, SARS2-32, SARS2-35 and SARS2-07 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Remarkably, several of the E484 escape mutants were resistant to neutralization at the highest concentration (1:80 initial dilution) of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), all but one show major resistance." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in all 4 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 152 virus from a chronically infected patient: although mAb C1A-B12 had no activity against this pseudotype, all three affinity optimized versions were active; the antibody containing the most mutations, C1A-B12.3, was the most potent (IC50 <0.5 μg/mL)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This Spike pseudotype for Day 152 virus from a chronically infected patient was completely resistent to REGN10933." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 152 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 152 S pseudotype was resistant to neutralization." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "3rd exposure to antigen by Delta (B.1.617.2) (n=24) breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a 3rd mRNA vaccine dose in individuals aged 21 –63 years, median age=30 years. Data collected 5.5 months after 2nd vaccination." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous." "" "" "" "Braeye" "2022" "https://doi.org/10.1101/2022.05.09.22274623" "doi:10.1101/2022.05.09.22274623" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In sera from 17 sero-positive blood donors, and 18 months post-infection (May 2020) sera from 17 health care workers in Sweden, a 40x drop in neutralization by Omicron (B.1.1.529) pseudotyped lentivirus was observed in HEK293T cells using the First WHO International Standard (20/136). Median IC50 reduction was ~6x for the blood donors, and ~4.5x for the health care workers." "" "" "" "Sheward" "2021" "https://drive.google.com/file/d/1CuxmNYj5cpIuxWXhjjVmuDqntxXwlfXQ/view" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous." "" "" "" "Braeye" "2022" "https://doi.org/10.1101/2022.05.09.22274623" "doi:10.1101/2022.05.09.22274623" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23071,23071,23074,23074,23075,23075,22992,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,S477N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using molecular dynamics simulation, ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations." "" "" "" "Zhang" "2022" "https://doi.org/10.1101/2022.06.05.493249" "doi:10.1101/2022.06.05.493249" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23012" "E484R,E484R" "" "YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This is a two point mutation change giving this position the highest possible fitness, has higher affinity than circulating E484K variant." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23012" "E484R,E484R" "" "YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23012" "E484R,E484R" "" "YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23012" "E484R,E484R" "" "YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23012" "E484R,E484R" "" "YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This is a two point mutation change giving this position the highest possible fitness, has higher affinity than circulating E484K variant." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23012" "E484R,E484R" "" "YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "As measured by surface plasmon resonance, RBD with the E484K mutation alone showed a mean 19.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Individual variants appearing at <=30% frequency at day 21 in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then appearing all at >95% frequency at day 27." "" "" "" "Chen" "2021" "https://doi.org/10.1101/2021.04.08.21254791" "doi:10.1101/2021.04.08.21254791" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in binding efficiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus)" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "E484K pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed a mean 2.8x decrease in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported moderate increase in affinity compared to wild-type RBD on the cell surface (Kd = 38.5nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Monoclonal antibodies 13G9 and 58G6 maintain fairly high neutralization potency, compared to others interfacing with E484K." "" "" "" "Li" "2021" "https://doi.org/10.1101/2021.04.19.440481" "doi:10.1101/2021.04.19.440481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Of 50 mAbs tested, major loss of neutralization observed for S2N28, S2X615, S2N12, S2X192, S2H7, S2X16, S2X58, S2H70, S2X613, S2D19, S2N22, S2D32, S2H58, S2M11, S2D106, S2X30." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Analyzing responses to the E484K mutation seen in B.1.351 and P.1 variants, we noted that it did not fall in a region predicted to bind the HLAII alleles tested (table S4). The mutation appeared to have no substantial or differential impact on T cell responses." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~16x binding against this isolated mutation. Casirivimab lost ~16x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, ELISA tests show 10x reduced efficacy of a majority of isolated antibodies, but only a modest decrease for vaccine plasma overall." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers of non-human primate sera after one or two doses of Ad26.COV2.S (Jannsen vaccine) against the variants containing the E484K substitution in the RBD were present but reduced (fold reduction between 3.35–7.78, 95% confidence interval all above twofold difference, one-sample t test)." "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Human sera from 5 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) neutralized this variant 3.4x less relative to reference USA-WA1/2020 strain. 8 convalescent plasma with weak IgG ELISA titre neutralized this variant 2.4x less relative to reference USA-WA1/2020 strain. One plasma failed to neutralize at all. 11 convalescent plasma with moderate IgG ELISA titre neutralized this variant 4.2x less relative to reference USA-WA1/2020 strain. 11 convalescent plasma with high IgG ELISA titre neutralized this variant 2.6x less relative to reference USA-WA1/2020 strain." "" "" "" "Jangra" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-02, 1B07, SARS2-16, SARS2-32, SARS2-35 and 2B04 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 15/20 convalescent sera was significantly lower against this pseudotyped virus model" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in all 4 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "This mutation occurred in 100% of sequenced virions after 12 passages and led to a 4-fold decrease in convalescent plasma neutralization activity" "" "" "" "Andreano" "2020" "https://doi.org/10.1101/2020.12.28.424451" "doi:10.1101/2020.12.28.424451" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape due to E484K [given Dec 2020-Apr 2021 time frame of the study, this is assumed to entail both Beta and Gamma lineages]." "" "" "" "Chung" "2021" "https://doi.org/10.1136/bmj.n1943" "doi:10.1136/bmj.n1943" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.3x reduction in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.6 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody VH-Fc ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "The only mutation in the B.1.351 lineage that appears to contribute to neutralization reduction (~1.7x across 10 convalescent sera from April 2020 infectees)" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus)" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2 antibodies C627, C602, C671, C643, and class 2/3 antibody C603 selected for the emergence of the E484K mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Multiple individuals in two related households were infected with a newly acquired E484K mutation within the B.1.311 lineage. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient's quarantine period." "" "" "" "Sabin" "2021" "https://doi.org/10.1101/2021.10.02.21264415" "doi:10.1101/2021.10.02.21264415" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484K conferred a ten-fold reduction in neutralisation by vaccine sera." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,22597,22597,22599" "E484K,E484K,R346K,R346K,R346K" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E484K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,22810,22810,22811,22812,22813,22813,22813" "E484K,E484K,K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~32x binding against this double mutation. COR-101 lost ~160x binding against this double mutation. Casirivimab lost ~16x binding against this double mutation. Estesevimab lost ~32x binding against this double mutation. Regdanvimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,22810,22810,22811,22812,22813,22813,22813,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "E484K,E484K,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~13x more infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,22810,22810,22811,22812,22813,22813,22813,23399,23401,23401,23402,23403,23403" "E484K,E484K,K417N,K417N,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Approximately as infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of the individual variants)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063" "E484K,E484K,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.5 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In the case of VOC B.1.1.7+E484K, the addition of the E484K mutation to N501Y further increased the affinity, to ~15 fold higher than WT RBD (KD ~5 nM), by further increasing the k(on) as measured by surface plasmon resonance. Because the higher k(on) could result in mass transfer limiting binding, we confirmed that the kinetic measurement for this variant was not substantially affected by varying levels of immobilization." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Omicron Molnupiravir (MK-4482) had no statistically significant change." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.025x fold change in IC50 in B.1.1.529 Omicron" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)]" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.0015x fold change in IC50 in B.1.1.529 Omicron" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.5 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.4 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 20 sera from BNT162b2 mRNA vaccine inoculated participants, 6 displayed mild (2x) reductions in neutralization. This variant combination showed the highest reduction, but the magnitude of the differences was small compared to the >4x differences in HA-inhibition titers that have been used to signal potential need for a strain change in influenza vaccines." "" "" "" "Xie" "2021" "https://doi.org/10.1038/s41591-021-01270-4" "doi:10.1038/s41591-021-01270-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)]" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Protection against symptomatic infection caused by Beta/Gamma (assumed by combined presence of N501Y and E484K) was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%)." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Viral load from oral swabs from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Viral load from lung tissue from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Omicron neutralizing antibodies is 0.686x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~100x folds more significant in 3 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Omicron neutralizing antibodies is 0.722x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~17.5x folds more significant in 9 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.4 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Values taken 28 days after booster dose was given for BBIBP-CorVvaccine to 390 participants with 130 participants in the 0-14d-10m, 0-21d-10m and 0-28d-10m group. The geometric mean titers (GMT) of neutralizing antibody in 0-28d-10m and 0-21d-10m group were significantly higher than 0-14d-10m group at month 3, month 6 and month 10 after the second dose. A sharply decrease by 4.85-fold (GMT: 94.4-20.3), 4.67-fold (GMT: 134.4-28.8) and 4.49-fold (GMT: 145.5-32.4) was observed from day 28 to month 10 after the second dose in 0-14d-10m, 0-21d-10m and 0-28d-10m group, respectively, and they had similar decline kinetics." "" "" "" "Yao T" "2022" "https://doi.org/10.1101/2022.06.22.22276690" "doi:10.1101/2022.06.22.22276690" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied]" "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~11x, Vero ~10x, and Calu-3 ~11x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~12x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of 501 and 484)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.618 was 2.7-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 3-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The estimated vaccine effectiveness against R.1 strain SARS-CoV-2 infection among residents in a Kentucky skilled nursing facility was 66.2% (95% CI = 40.5%–80.8%) and among health care workers was 75.9% (95% CI = 32.5%–91.4%) in the cohort of only those 14d+ post-vaccination Pfizer booster dose. VE against symptomatic COVID-19 was 86.5% (95% CI = 65.6%–94.7%) among residents and 87.1% (95% CI = 46.4%–96.9%) among HCP. VE against hospitalization was 94.4% (95% CI = 73.9%–98.8%) among residents; no HCP were hospitalized. Three residents died, two of whom were unvaccinated (VE = 94.4%; 95% CI = 44.6%–99.4%)." "" "" "" "Cavanaugh" "2021" "https://doi.org/10.15585/mmwr.mm7017e2" "doi:10.15585/mmwr.mm7017e2" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Pseudotyped viruses for B.1.618 was 2.5-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. [details on the convalescent patient sera collection are not abundantly clear in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403,25088" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,V1176F" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped P.2 virus has reduced neutralization activity vs wild type: 5.8x (30 sera Pfizer median 9 days post 2nd dose) and 2.9x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403,25088" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,V1176F" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the P.1 & P.2 lineages of SARS-CoV-2 in Brazil. The Brazilian arm of the Phase 3 double blind study showed severe/critical disease VE of 81.9% (95% CI: 17.0-98.1), and moderate to severe/critical disease VE of 66.2% (95% CI: 51.0-77.1). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 69.3% of mostly severe infections sequenced as of this report, 69.4% were of P.2 lineage [defining lineage SNPs reported here]." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403,25088" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,V1176F" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs]" "" "" "" "Sapkal" "2021" "https://doi.org/10.1101/2021.04.30.441559" "doi:10.1101/2021.04.30.441559" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403,25088" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,V1176F" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs]" "" "" "" "Sapkal" "2021" "https://doi.org/10.1101/2021.04.30.441559" "doi:10.1101/2021.04.30.441559" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484T" "" "YP_009724390.1:p.Glu484Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 3 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, E484Q shows a notably resistant profile, comparable to or even more resistant than E484K at later time points (i.e. more resistant to immune cell somatic mutation evolution), see Figure 5a,b. Subject C 32 days post-infection showed >>10 fold reduction in neutralization, reducing to ~10-fold by day 104. Subject B 26 days post-infection showed ~10 fold reduction in neutralization, reducing to ~4x at day 113. Notably, Subject B also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 32, and no E484K immune escape at day 104. Subject I 26 days post-infection showed ~10 fold reduction in neutralization, with no reduction in escape at day 102. Notably, Subject I also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 26, and no E484K immune escape at day 102." "" "" "" "Greaney" "2021" "https://doi.org/10.1016/j.chom.2021.02.003" "doi:10.1016/j.chom.2021.02.003" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a 10x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">20% (ELISA significance threshold) drop in antibody binding by this variant against monoclonal antibody VH-Fc ab8." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~20x binding against this isolated mutation. Casirivimab lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484T" "" "YP_009724390.1:p.Glu484Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484T" "" "YP_009724390.1:p.Glu484Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23401,23402,23403,23403" "E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~4x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23401,23402,23403,23403" "E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, RBD-specific mutation E484Q did not significantly confer infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23401,23402,23403,23403" "E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23401,23402,23403,23403" "E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 1.34x drop in neutralization (NT50) [mostly from a single serum]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23017,23018" "F486P,F486P" "" "YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23017,23018" "F486P,F486P" "" "YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.22 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23017,23018" "F486P,F486P" "" "YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23017,23018" "F486P,F486P" "" "YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutation causes a greater than 100x fold change in IC50 of Ensovibep." "" "" "" "Rothenberger" "2021" "https://doi.org/10.1101/2021.02.03.429164v4" "doi:10.1101/2021.02.03.429164v4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486A" "" "YP_009724390.1:p.Phe486Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486H" "" "YP_009724390.1:p.Phe486His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.05 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed in 4 separate mink farms in Denmark, but not humans, potential adaptation (diff set of farms than N501T)." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486A" "" "YP_009724390.1:p.Phe486Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Most effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutation causes a greater than 100x fold change in IC50 of Ensovibep." "" "" "" "Rothenberger" "2021" "https://doi.org/10.1101/2021.02.03.429164v4" "doi:10.1101/2021.02.03.429164v4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-07, SARS2-19, 1B07, SARS2-16 and 2B04 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "IC50 relative to wildtype drops ~8x in neutralization efficiency between 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.13 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 1 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed striking resistance with only 38% neutralization at the highest concentration tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">60% drop in antibody binding (ELISA) by this variant against monoclonal antibody VH-Fc ab8." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Modest decrease in in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 5 antibodies." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23023" "N487K" "NC_045512.2:g.1461T>G" "YP_009724390.1:p.Asn487Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, high ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Based on structural modelling, this change detected on day 128 sequencing in a chronically infected patient would alter an extensive network of polar interactions with antibody residue R94VH, a germline antibody residue that is conserved in all of the potent VH3-53/3-66-derived antibodies isolated from a convalescent donor 5 weeks after infection." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.11 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (3 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2/3 mAb C603 modestly selected for the emergence of this mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 3 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-32." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23062,23063,23063" "Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 146 virus from a chronically infected patient: resistant to neutralization by mAb C1A-B12, and was still resistant to the affinity enhanced antibodies derived from it (i.e. no affinity maturation effect on neutralization)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23062,23063,23063" "Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This Spike pseudotype for Day 146 virus from a chronically infected patient was completely resistent to REGN10933. The variant had a 4-fold decrease in REGN10987 neutralization sensitivity (2nd component of the Regeneron mAb cocktail)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23062,23063,23063" "Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 146 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 146 S pseudotype was resistant to neutralization." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs X593, 261-262, H4, and P2B-2F6" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) resistant to 3 individual sera at >4x" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490P" "" "YP_009724390.1:p.Phe490Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490P" "" "YP_009724390.1:p.Phe490Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490V" "NC_045512.2:g.1468T>G" "YP_009724390.1:p.Phe490Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 23% of supernatant sequences) after C121 monoclonal antibody assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490P" "" "YP_009724390.1:p.Phe490Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Dominant (70%) in day 21 of prolonged infection in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then nearly disappearing (<5%) by day 27." "" "" "" "Chen" "2021" "https://doi.org/10.1101/2021.04.08.21254791" "doi:10.1101/2021.04.08.21254791" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in binding efficiency vs wild type for mAbs CB6/LY-CoV16 and LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2 mAb C627 modestly selected for the emergence of this mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-01 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using molecular dynamic simulation, the mildly (~1kcal/mol) enhanced binding energy of this variant is primarily contributed by Tyr505 (−4.98 kcal/mol) which is now involved in a strong hydrogen bonding network with Arg393. Another important energetic contribution comes from the altered orientation of Tyr41 which is now involved with two hydrogen-bonding interactions with Asp355 and Thr500." "" "" "" "" "2021" "https://doi.org/10.1016/j.bbrc.2021.01.035" "doi:10.1016/j.bbrc.2021.01.035" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 2 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, S484P shows a slightly resistant profile across both timepoints (i.e. resistant to immune cell somatic mutation evolution)" "" "" "" "Greaney" "2021" "https://doi.org/10.1016/j.chom.2021.02.003" "doi:10.1016/j.chom.2021.02.003" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Regdanvimab lost ~32x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Minor variant selected in late rounds of an in vitro evolution experiment for ACE2 binding. Shown to increase the thermostability but decrease the association rate constant of the RBD to ACE2" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23048" "G496S" "NC_045512.2:g.1486G>A" "YP_009724390.1:p.Gly496Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063" "Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. The extent of affinity increase with Q498R and N501Y is not exactly quantified, as E484K always emerged with this duo during in vitro evolution." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.69 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In 30 samples collected 111 to 260 days post onset of symptoms, the covalescent plasma can neutralize both the reference USA-WA1/2020 strain and the mouse adapted strain that contains the N501Y spike mutation with similar efficiency." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation alone accounts for most of the increased infectivity of the Alpha variant, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters, and Vero E6 (NHP) and Calu-3 (human) cell lines." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.03.08.434499" "doi:10.1101/2021.03.08.434499" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slightly increased infection rate amongst the cells. [in what is essentially a replicate experiment in the same paper, because each B.1.351 lineage variant was independetly evaluated and N501 is in both lineages, a significant decrease was observed, therefore the error bars described in this paper should be interpreted carefully]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "0.7x reduction in neutralization by key variant in several variants of concern in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Human sera from 6 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) can neutralize both the reference USA-WA1/2020 strain and the mouse adapted SARS-CoV-2 strain that contains the N501Y spike mutation with similar efficiency." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape by lineage Alpha [defined here as N501Y positive, but E484K negative]." "" "" "" "Chung" "2021" "https://doi.org/10.1136/bmj.n1943" "doi:10.1136/bmj.n1943" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome" "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a modest decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Contrary to other reports on N501Y containing lineages (i.e. with additional mutations), N501Y alone may have an even greater affinity for a human monoclonal antibody specific for wild type. These results suggest that the individual N501Y mutation does not contribute to altered viral properties by itself, but may contribute to a collective conformational shift produced by multiple mutations." "" "" "" "Klegerman" "2021" "https://doi.org/10.1101/2021.04.26.441517" "doi:10.1101/2021.04.26.441517" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x)" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.2x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 and day 14 post-2nd dose) against a recombinant single variant virus (modified replicating WA-1 cDNA clone) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In silico methods (PyMOL and PDBePISA) involving mutagenesis (N501Y mutation) and interface analysis focusing on the Spike RDB-ACE2 interaction showed that the SARS-CoV-2 N501Y mutant (lineage B.1.1.7) establishes a more significant number of interactions relating to the mutant residue Y501 (Spike RDB) with residues Y41 and K353 (ACE2). This finding shows that the increased infectivity of SARS-CoV-2 lineage B.1.1.7 is associated with the interaction force between the Spike RBD Y501 mutant residue with the ACE2 receptor, which in this strain is increased." "" "" "" "" "2021" "https://doi.org/10.1101/2020.12.29.424708" "doi:10.1101/2020.12.29.424708" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Of 50 mAbs tested, major loss of neutralization observed for S2X128, S2D8, S2X192, S2D19, S2H14, S2H19." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x)" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C663, and to a lesser extent C613." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Utilizing shark derived vnarbodies, S375F mutation on Omicron RBD disrupts the structure of β-strand, which inhibits binding with 20G6. 20G6 binds to a hidden epitope on RBD which is highly conserved in sarbecoviruses." "" "" "" "Feng" "2022" "https://doi.org/10.1002/smtd.202200387" "doi:10.1002/smtd.202200387" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The N501Y mutation had the biggest effect on ACE2 affinity of any VOC mutation tested, increasing the affinity ~10 fold to KD ~7 nM, by increasing the k(on) ~1.8 fold and decreasing the k(off) by ~ 7 fold as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "As measured by surface plasmon resonance, RBD with the N501Y mutation alone showed a mean 2.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Vaccinated, but not post-infection sera, show decreased average T cell response to an N501Y peptide. When we primed transgenic mice expressing human HLA-DRB1*0401 with the Wuhan Hu-1 peptide pool, T cell responses to the B.1.1.7 variant peptide pool were significantly reduced (p = 0.0286). Furthermore, the T cell response to the spike N501Y mutation common to all three of the current VOC was ablated." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The most frequent RBM mutation N501Y (165,519 instances) makes defective the atypical N-glycosylation sequon NGV 501-503, becoming a key RBM position for the interaction with hACE2-binding hotspot 353." "" "" "" "Gamez" "2021" "https://doi.org/10.1101/2021.04.09.439154" "doi:10.1101/2021.04.09.439154" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "Variant within the six key residues in the receptor binding domain (RBD). Independently reported in UK, Australia (same origin as UK), and South Africa (independent origin)." "" "" "" "Flores-Alanis" "2021" "https://doi.org/10.3390/pathogens10020184" "doi:10.3390/pathogens10020184" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~8x binding against this isolated mutation. Regdanvimab lost ~6x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Lowered the neutralization potency of mAb COVA1-12 to the limit of the assay. Decrease in potency was observed against the N501Y pseudotype for the cluster IX mAb COVA2-17." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,22810,22810,22811,22812,22813,22813,22813" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~20x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~6x binding against this double mutation. M396 lost ~10x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,22810,22810,22811,22812,22813,22813,22813,23011,23012" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In post-vaccination sera from individuals who received one (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) of the BNT162b2 Pfizer vaccine, an average 6.8x reduction in neutralization efficacy of this B.1.351 key variants pseudotype lentivirus vs D614G was observed." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,22810,22810,22811,22812,22813,22813,22813,23011,23012" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "~7x reduction in neutralization by key B.1.351 lineage RBD variant combination in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Two of the cohort showed no neutralization against this variant." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23011,23012" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~64x binding against this double mutation. COR-101 lost ~50x binding against this double mutation. Casirivimab lost ~250x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~32x binding against this double mutation. Tixagevimab lost ~10x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23271" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Partial sequencing of S gene reveals two cases of probable early 2021 B.1.1.7 lineage reinfection from non-B.1.1.7 original cases in Lombardy, with 45 to 90 days between infections (less than the typical 90 day guideline for this call). Patients were 56 and 58yo, immunocompenent, with one a former smoker with obesity and dyslipidemia. One case required intubation during first infection, but presented with mild symptoms upon reinfection. The other case convalesced at home during the first episode, but required CPAP support in the subacute clinical unit upon reinfection." "" "" "" "Novazzi" "2021" "https://doi.org/10.1002/jmv.27066" "doi:10.1002/jmv.27066" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed no change in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~9x, Vero ~8x, and Calu-3 ~8x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~13x, Vero ~10x, and Calu-3 ~10x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells for ACE2 affinity changes vs D614G alone, showing a ~70% drop in IC50 (i.e. increased affinity)." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H (""Ohio"") lineage was neutralized similarly to D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23071,23071,23074,23074,23075,23075" "Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed first in a single tiger (cohort of 5), potential adaptation." "" "" "" "McAloose" "2020" "https://doi.org/10.1128/mBio.02220-20" "doi:10.1128/mBio.02220-20" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23071,23071,23074,23074,23075,23075" "Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23075" "Y505Q" "" "YP_009724390.1:p.Tyr505Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23102" "S514T" "NC_045512.2:g.1540T>A" "YP_009724390.1:p.Ser514Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23108" "E516Q" "NC_045512.2:g.1546G>C" "YP_009724390.1:p.Glu516Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23115" "L518Q" "NC_045512.2:g.1553T>A" "YP_009724390.1:p.Leu518Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23120" "A520S" "NC_045512.2:g.1558G>T" "YP_009724390.1:p.Ala520Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "CR3022 (SARS-targeting mAb) cross-reactivity lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23148" "K529T" "NC_045512.2:g.1586A>C" "YP_009724390.1:p.Lys529Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant raises PIWAS epitope score from 3.6% to 6.2% (improved immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated that there is very little free energy change (ddG. -0.02 kcal/mol) for this variant (i.e. approx. same stability as wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing statistically significant increased infection rate amongst the cells." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23373" "T604I" "NC_045512.2:g.1811C>T" "YP_009724390.1:p.Thr604Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a lentivirus virus pseudotyped with D614G Spike, sera from vaccinated individuals who received the second dose (9–11 days post-second dose of Pfizer) exhibited a robust neutralizing potential, with a mean NT50 value of 99,000. This was an average of a 2-fold increase, relative to sera drawn from the individuals who received one dose of vaccination—mean NT50 dilution of 51,300. Importantly, a 6-fold increase in mean NT50 dilution was obtained when sera from the first vaccination dose was compared to convalescent sera from cohort with severe disease (NT50 51,000 vs 8,700) 21 to 63 days post-onset." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Weissman" "2020" "https://doi.org/10.1101/2020.07.22.20159905" "doi:10.1101/2020.07.22.20159905" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 1.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation (a.k.a. ""Doug"") outside the receptor binding domain, while highly favorable to improved human-human transmission, decreases transduction in naked mole-rat (Heterocephalus glaber) fibroblast and Japanese pipistrelle bat (Pipistrellus abramus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to wild type, D614G showed increased infectivity (ie. cold stability) after storage at -20°C for up to 30 days." "" "" "" "Huang" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 conferred a nearly two-fold infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 2.5 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD mutation conferred a 4.85x drop in neutralization (NT50)." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In four cell lines (including 293T-hACE2 cells), this mutation combination increases infectivity vs D614G alone" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission." "" "" "" "Plante" "2020" "https://doi.org/10.1038/s41586-020-2895-3" "doi:10.1038/s41586-020-2895-3" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.35x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses." "" "" "" "Ozono" "2020" "https://doi.org/10.1038/s41467-021-21118-2" "doi:10.1038/s41467-021-21118-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a slight decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses." "" "" "" "Ozono" "2020" "https://doi.org/10.1038/s41467-021-21118-2" "doi:10.1038/s41467-021-21118-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The increased transduction with Spike D614G ranged from 1.3- to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2 and from 1.5- to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction." "" "" "" "Daniloski" "2021" "https://doi.org/10.7554/eLife.65365" "doi:10.7554/eLife.65365" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped D614G virus has reduced neutralization activity vs wild type: 1.2x (37 sera Pfizer median 9 days post 2nd dose, 37 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.05x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.45x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.43x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.97x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Weissman" "2020" "https://doi.org/10.1101/2020.07.22.20159905" "doi:10.1101/2020.07.22.20159905" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.53x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Studying 94 COVID-19 extended infection cases with genomics April 1 to October 17, 2020, one case developed 23 mutations in a 19 day period, including this combination in Spike." "" "" "" "Landis" "2021" "https://doi.org/10.1101/2021.05.08.21256775" "doi:10.1101/2021.05.08.21256775" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21575" "D614G,D614G,D614G,D614G,D614G,D614G,L5F" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.23x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21575" "D614G,D614G,D614G,D614G,D614G,D614G,L5F" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.1x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21575" "D614G,D614G,D614G,D614G,D614G,D614G,L5F" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21575,21846,22317,22319,22320,23011,23012,23664" "D614G,D614G,D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,E484K,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.526) showed a 1.02x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21575,21846,22317,22319,22320,23011,23012,23664" "D614G,D614G,D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,E484K,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.526) showed a 1.78x increase in binding (KD) relative to D614G, even though each variant independently decreases binding." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21575,21846,22317,22319,22320,23011,23012,23664" "D614G,D614G,D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,E484K,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.526) showed a 1.34x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21600" "D614G,D614G,D614G,D614G,D614G,D614G,S13I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.42x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21600" "D614G,D614G,D614G,D614G,D614G,D614G,S13I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21600" "D614G,D614G,D614G,D614G,D614G,D614G,S13I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21600,22018,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.429 aka Epsilon) showed a 2.82x increase in binding (KD) relative to D614G, indicating a strong marginal effect for L452R." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21600,22018,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. [Stark contrast to 2.15x increase in binding by convalescent plasma 8 months post infection, presumably via memory B cell affinity maturation against L452R effects] 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21600,22018,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, indicating ablated marginal effect from L452R." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614" "D614G,D614G,D614G,D614G,D614G,D614G,L18F" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.07x decrease in binding (KD) relative to D614G. Compare to increased binding in full Spike variant complements for major lineages containing this variant subset: 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614" "D614G,D614G,D614G,D614G,D614G,D614G,L18F" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.30x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.28x increase (B.1.351 aka Beta), and 1.14x decrease (P.1 aka Gamma). 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.17x increase (B.1.351 aka Beta), and 1.47x decrease (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614" "D614G,D614G,D614G,D614G,D614G,D614G,L18F" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.66x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Compare to decreased binding in full Spike variant complements for major lineages containing this variant subset: 0.96x (B.1.351 aka Beta), 0.77x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "D614G,D614G,D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing P.1 aka Gamma) showed a 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "D614G,D614G,D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing P.1 aka Gamma) showed a 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "D614G,D614G,D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing P.1 aka Gamma) showed a 4.24x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614,21801,23060,23061,23062,23062,23063,23063,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23664" "D614G,D614G,D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.351 aka Beta) showed a 3.56x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614,21801,23060,23061,23062,23062,23063,23063,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23664" "D614G,D614G,D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing B.1.351 aka Beta) showed a 1.28x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. It shows a 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614,21801,23060,23061,23062,23062,23063,23063,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23664" "D614G,D614G,D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing B.1.351 aka Beta) showed a 1.04x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, in contrast to the largely positive binding values for each individual mutation that comprises the set." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21621" "D614G,D614G,D614G,D614G,D614G,D614G,T20N" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.96x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21621" "D614G,D614G,D614G,D614G,D614G,D614G,T20N" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.39x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21621" "D614G,D614G,D614G,D614G,D614G,D614G,T20N" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21638" "D614G,D614G,D614G,D614G,D614G,D614G,P26S" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.23x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21638" "D614G,D614G,D614G,D614G,D614G,D614G,P26S" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21638" "D614G,D614G,D614G,D614G,D614G,D614G,P26S" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.58x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.33x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.51x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing B.1.1.7 aka Alpha) showed no change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.28x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing B.1.1.7 aka Alpha) showed a 1.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.1.7 aka Alpha) had 5.43x increased binding relative to D614G alone." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21801" "D614G,D614G,D614G,D614G,D614G,D614G,D80A" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination showed no change relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21801" "D614G,D614G,D614G,D614G,D614G,D614G,D80A" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21801" "D614G,D614G,D614G,D614G,D614G,D614G,D80A" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.64x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.35x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21846" "D614G,D614G,D614G,D614G,D614G,D614G,T95I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21846" "D614G,D614G,D614G,D614G,D614G,D614G,T95I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21846" "D614G,D614G,D614G,D614G,D614G,D614G,T95I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21974" "D614G,D614G,D614G,D614G,D614G,D614G,D138Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21974" "D614G,D614G,D614G,D614G,D614G,D614G,D138Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.32x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21974" "D614G,D614G,D614G,D614G,D614G,D614G,D138Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22018" "D614G,D614G,D614G,D614G,D614G,D614G,W152C" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22018" "D614G,D614G,D614G,D614G,D614G,D614G,W152C" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.03x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22018" "D614G,D614G,D614G,D614G,D614G,D614G,W152C" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.15x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22132" "D614G,D614G,D614G,D614G,D614G,D614G,R190S" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.59x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22132" "D614G,D614G,D614G,D614G,D614G,D614G,R190S" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22132" "D614G,D614G,D614G,D614G,D614G,D614G,R190S" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.82x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22206" "D614G,D614G,D614G,D614G,D614G,D614G,D215G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.79x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22206" "D614G,D614G,D614G,D614G,D614G,D614G,D215G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.19x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22206" "D614G,D614G,D614G,D614G,D614G,D614G,D215G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D614G,D614G,D253G,D253G,D253G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.08x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D614G,D614G,D253G,D253G,D253G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D614G,D614G,D253G,D253G,D253G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22810,22810,22811,22812,22813,22813,22813" "D614G,D614G,D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22810,22810,22811,22812,22813,22813,22813" "D614G,D614G,D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22810,22810,22811,22812,22813,22813,22813" "D614G,D614G,D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.76x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.75x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22812,22812" "D614G,D614G,D614G,D614G,D614G,D614G,K417T,K417T" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22812,22812" "D614G,D614G,D614G,D614G,D614G,D614G,K417T,K417T" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.28x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22812,22812" "D614G,D614G,D614G,D614G,D614G,D614G,K417T,K417T" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.05x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.16x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.66x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22783,22783,22784,22785,22786,22786,22679,22679,22686,22992,22992,22995,23071,23071,23074,23074,23075,23075" "D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,R408S,S373P,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 78fM for binding to the Omicron BA.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22783,22783,22784,22785,22786,22786,22679,22679,22686,22992,22992,22995,23071,23071,23074,23074,23075,23075" "D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,R408S,S373P,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 4.5-fold lower (95% CI: 4.3x-4.7x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22783,22783,22784,22785,22786,22786,22679,22679,22686,22992,22992,22995,23071,23071,23074,23074,23075,23075" "D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,R408S,S373P,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 3.9x-fold lower (95% CI: 0.14x-0.17x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22917,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22783,22783,22784,22785,22786,22786,22679,22679,22686,22992,22992,22995,23071,23071,23074,23074,23075,23075" "D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,R408S,S373P,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 4.2-fold lower (95% CI: 5.8x-6.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22917,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22783,22783,22784,22785,22786,22786,22679,22679,22686,22992,22992,22995,23071,23071,23074,23074,23075,23075" "D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,R408S,S373P,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 3.9x-fold lower (95% CI: 0.14x-0.18x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23011,23012" "D614G,D614G,D614G,D614G,D614G,D614G,E484K,E484K" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.42x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23011,23012" "D614G,D614G,D614G,D614G,D614G,D614G,E484K,E484K" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23011,23012" "D614G,D614G,D614G,D614G,D614G,D614G,E484K,E484K" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This variant appears twice in the experiments, with slightly different affinities (both ~1.2x decrease in binding relative to D614G) using flow cytometry and ACE2 ectodomains-Fc portion IgG complex." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23060,23061,23062,23062,23063,23063" "D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23060,23061,23062,23062,23063,23063" "D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23060,23061,23062,23062,23063,23063" "D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.52x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis). Compare to full Spike variant complements for major lineages containing this variant subset: 5.43x (B.1.1.7 aka Alpha), 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23271" "D614G,D614G,D614G,D614G,D614G,D614G,A570D" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23271" "D614G,D614G,D614G,D614G,D614G,D614G,A570D" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.18x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23271" "D614G,D614G,D614G,D614G,D614G,D614G,A570D" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.21x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.48x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23604,23604" "D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23604,23604" "D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23604,23604" "D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.26x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23604,23604" "D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant change in virus neutralzation by 18 Pfizer two dose vaccinee sera compared to B.1.1.7. [results without including the used mutation A27S likely generalizable, as this is not a lineage defining mutation]" "" "" "" "Zuckerman" "2021" "https://doi.org/10.1101/2021.03.25.21253908" "doi:10.1101/2021.03.25.21253908" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23664" "D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23664" "D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23664" "D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed essentially no change in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23709" "D614G,D614G,D614G,D614G,D614G,D614G,T716I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23709" "D614G,D614G,D614G,D614G,D614G,D614G,T716I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.58x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23709" "D614G,D614G,D614G,D614G,D614G,D614G,T716I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.12x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24506" "D614G,D614G,D614G,D614G,D614G,D614G,S982A" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24506" "D614G,D614G,D614G,D614G,D614G,D614G,S982A" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.3x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24506" "D614G,D614G,D614G,D614G,D614G,D614G,S982A" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24642" "D614G,D614G,D614G,D614G,D614G,D614G,T1027I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.56x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24642" "D614G,D614G,D614G,D614G,D614G,D614G,T1027I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.69x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24642" "D614G,D614G,D614G,D614G,D614G,D614G,T1027I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.22x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24914" "D614G,D614G,D614G,D614G,D614G,D614G,D1118H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24914" "D614G,D614G,D614G,D614G,D614G,D614G,D1118H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24914" "D614G,D614G,D614G,D614G,D614G,D614G,D1118H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.96x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23429" "A623T" "NC_045512.2:g.1867G>A" "YP_009724390.1:p.Ala623Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23521,23522,23524,23524,23525,23525" "H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.87 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23521,23522,23524,23524,23525,23525" "H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23521,23522,23524,23524,23525,23525" "H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Six minks were intranasally infected with WA1 isolate, all developed this mutation during infection." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23521,23522,23524,23524,23525,23525" "H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain increases the virus transduction rate in tree shrew (Tupaia belangeri), (as it does in humans) according to pseudotyped VSV experiments." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23587,23587,23587" "Q675H,Q675H,Q675H" ",NC_045512.2:g.2025G>C,NC_045512.2:g.2025G>T" "YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly enhanced the ability of the pseudotyped VSV to infect fat-tailed gerbil (Pachyuromys duprasi) kidney cell cultures, with a transduction rate of 13.4%, close to the 15.7% in epithelial-like human Huh-7 cells while starting from a significantly lower wildtype (Wuhan-Hu-1 Spike VSVdeltaG psuedotype) rate." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681R,P681R" "NC_045512.2:g.2042C>G," "YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. [PG: Inferred by conservative AA substitution of described P681H]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic." "" "" "" "Johnson" "2020" "https://doi.org/10.1101/2020.08.26.268854" "doi:10.1101/2020.08.26.268854" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "While the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC)." "" "" "" "Lubinski" "2021" "https://doi.org/10.1101/2021.04.06.438731" "doi:10.1101/2021.04.06.438731" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In the absence of N501Y, this Alpha lineage change in the furin clevage site did NOT show significant increase in infectivity relative to wild type, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.03.08.434499" "doi:10.1101/2021.03.08.434499" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic." "" "" "" "Johnson" "2020" "https://doi.org/10.1101/2020.08.26.268854" "doi:10.1101/2020.08.26.268854" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681R,P681R" "NC_045512.2:g.2042C>G," "YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). [Inference from similar positively charged substitution P681H actually described in the work]" "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 0.9x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry)." "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry)." "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing NO statistically significant infection rate change amongst the cells, suggesting that furin cleavage typically used for cell entry is not affected by this change one amino acid upstream of the RXXR recognition pattern." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604,23399,23401,23401,23402,23403,23403" "P681R,P681R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Quantification of the band intensities showed that the P681R mutation, which lies near the proteolytic processing site, caused a small increase in proteolytic processing as measured by a 2-fold decrease in the ratio of S/S2." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23664" "A701V" "NC_045512.2:g.2102C>T" "YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23664" "A701V" "NC_045512.2:g.2102C>T" "YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.33 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant increases PIWAS epitope score from 0.69% to 2.3% Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain showed a decreased capacity to transduce PK-15 (pig kidney, Sus scrofa) and PaKi (black flying fox kidney, Pteropus alecto) cell line cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed first in a single tiger (cohort of 5), potential adaptation." "" "" "" "McAloose" "2020" "https://doi.org/10.1128/mBio.02220-20" "doi:10.1128/mBio.02220-20" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. T716I was expressed at significantly lower level, accounting for the decreased infectivity of this spike protein. This property may be specific to spike protein biosynthesis in 293T cells and is not likely to reflect the situation in vivo given the reported increase in infectivity of the B.1.1.7 virus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23897" "Q779K" "NC_045512.2:g.2335C>A" "YP_009724390.1:p.Gln779Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 20% appearance in 2 passages against Regeneron monoclonal antibody RGN10989 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23948" "D796H" "NC_045512.2:g.2386G>C" "YP_009724390.1:p.Asp796His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Fatal COVID-19 complications in immunocomprimised patient after immune escape from convalescent plasma" "" "" "" "Kemp" "2020" "https://doi.org/10.1101/2020.12.05.20241927" "doi:10.1101/2020.12.05.20241927" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24000" "S813I" "NC_045512.2:g.2438G>T" "YP_009724390.1:p.Ser813Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb B38" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24077" "D839Y" "NC_045512.2:g.2515G>T" "YP_009724390.1:p.Asp839Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry." "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24077" "D839N" "NC_045512.2:g.2515G>A" "YP_009724390.1:p.Asp839Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry." "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24130" "N856K" "NC_045512.2:g.2568C>A" "YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch." "" "" "" "Lucaci" "2021" "" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24170" "I870V" "NC_045512.2:g.2608A>G" "YP_009724390.1:p.Ile870Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Appeared at same time as T478K,S494P but listed separately due to distance and different domains affected in the Spike (i.e. putatively an independent mutation from a functional standpoint since the former are from S1, the latter from S2)." "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24377,24378,24378" "S939F,S939F,S939F" "NC_045512.2:g.2816C>T,NC_045512.2:g.2816C>T," "YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (70%) increase in infection rate amongst the cells, hence this individual variant is likely to significantly contribute to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 6/20 convalescent sera was significantly lower against this single variant pseudotyped virus model, showing similar patterns to the pseudotyped virus model of B.1.1.7." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24642" "T1027I" "NC_045512.2:g.3080C>T" "YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 1.51 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Mutation is predicted to lose the T cell epitope for people carrying DRB1*0301 and DRB1*0401, but not for example in those who are DRB1*0701 or DRB1*1501 who would be predicted to show an enhanced response. This is also observed in a study of 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25045,25046,25046" "P1162S,P1162S,P1162S" "" "YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25249,25249,25249" "M1229I,M1229I,M1229I" "NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25350" "P1263L" "NC_045512.2:g.3788C>T" "YP_009724390.1:p.Pro1263Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant in the cytoplasmic tail, shown in vitro to increase Spike subunit fusion required for cell entry" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25855" "D155Y" "NC_045512.2:g.463G>T" "YP_009724391.1:p.Asp155Tyr" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "caveolin binding" "" "" "In silico, this mutation is the only one weakening ORF3a's binding affinity for caveolin-1 (essential for entry and endomembrane trafficking of SARS-CoV-2). This mutation is a widespread homoplasy in 20A and 20B lineages." "" "" "" "Gupta" "2021" "https://doi.org/10.1101/2021.03.26.437194" "doi:10.1101/2021.03.26.437194" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26029" "Q213K" "NC_045512.2:g.637C>A" "YP_009724391.1:p.Gln213Lys" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*01:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26029" "Q213K" "NC_045512.2:g.637C>A" "YP_009724391.1:p.Gln213Lys" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*01:01-restricted CD8+ ORF3a epitope, which is otherwise ""consistently dominant and of high magnitude""." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26256" "F4F" "NC_045512.2:g.12C>T" "YP_009724392.1:p.Phe4Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26268,26268,26269,26270" "T9I,T9I,T9I,T9I" ",NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T" "YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~300 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26268,26268,26269,26270" "T9I,T9I,T9I,T9I" ",NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T" "YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26295,26296" "L18I,L18I" ",NC_045512.2:g.52C>A" "YP_009724392.1:p.Leu18Ile,YP_009724392.1:p.Leu18Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (47x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26299" "L19F" "NC_045512.2:g.55C>T" "YP_009724392.1:p.Leu19Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26312" "F23C" "NC_045512.2:g.68T>G" "YP_009724392.1:p.Phe23Cys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~8.8 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26314" "V24M" "NC_045512.2:g.70G>A" "YP_009724392.1:p.Val24Met" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26319" "V25V" "NC_045512.2:g.75A>G" "YP_009724392.1:p.Val25Val" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (45x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26333" "T30I" "NC_045512.2:g.89C>T" "YP_009724392.1:p.Thr30Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26353" "L37F" "NC_045512.2:g.109C>T" "YP_009724392.1:p.Leu37Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26395" "L51I" "NC_045512.2:g.151C>A" "YP_009724392.1:p.Leu51Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (47x overrepresentation vs expected count of ~24 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26416" "V58L" "NC_045512.2:g.172G>C" "YP_009724392.1:p.Val58Leu" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26428" "V62F" "NC_045512.2:g.184G>T" "YP_009724392.1:p.Val62Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (18x overrepresentation vs expected count of ~333 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26442" "N66K" "NC_045512.2:g.198T>G" "YP_009724392.1:p.Asn66Lys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~23 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26447" "S68F" "NC_045512.2:g.203C>T" "YP_009724392.1:p.Ser68Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26447" "S68C" "NC_045512.2:g.203C>G" "YP_009724392.1:p.Ser68Cys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (58x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26456" "P71R" "NC_045512.2:g.212C>G" "YP_009724392.1:p.Pro71Arg" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26466,26467" "V75L,V75L" ",NC_045512.2:g.223G>C" "YP_009724392.1:p.Val75Leu,YP_009724392.1:p.Val75Leu" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (3762.7x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526" "A2S" "NC_045512.2:g.4G>T" "YP_009724393.1:p.Ala2Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (38x overrepresentation vs expected count of ~334 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526" "A2S" "NC_045512.2:g.4G>T" "YP_009724393.1:p.Ala2Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Emergent as 16% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing." "" "" "" "Avanzato" "2020" "https://doi.org/10.1016/j.cell.2020.10.049" "doi:10.1016/j.cell.2020.10.049" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526,26527,26529" "D3H,D3H,D3H" "NC_045512.2:g.7G>C,NC_045512.2:g.7G>C,NC_045512.2:g.7G>C" "YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (227x overrepresentation vs expected count of ~14 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26528,26528,26528" "A2A,A2A,A2A" "NC_045512.2:g.6A>T,NC_045512.2:g.6A>G,NC_045512.2:g.6A>C" "YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (25x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26530" "D3G" "NC_045512.2:g.8A>G" "YP_009724393.1:p.Asp3Gly" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (31x overrepresentation vs expected count of ~53 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26542" "T7I" "NC_045512.2:g.20C>T" "YP_009724393.1:p.Thr7Ile" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26546" "I8I" "NC_045512.2:g.24T>C" "YP_009724393.1:p.Ile8Ile" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~80 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26573,26573,26576,26576,26577,26577" "Q19E,Q19E,Q19E,Q19E,Q19E,Q19E" "" "YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~8 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26620" "C33S" "NC_045512.2:g.98G>C" "YP_009724393.1:p.Cys33Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~32 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26645" "N41N" "NC_045512.2:g.123C>T" "YP_009724393.1:p.Asn41Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (19x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26681" "F53F" "NC_045512.2:g.159C>T" "YP_009724393.1:p.Phe53Phe" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (163x overrepresentation vs expected count of ~567 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26730" "V70L" "NC_045512.2:g.208G>C" "YP_009724393.1:p.Val70Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26748" "I76L" "NC_045512.2:g.226A>C" "YP_009724393.1:p.Ile76Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~9 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26748" "I76V" "NC_045512.2:g.226A>G" "YP_009724393.1:p.Ile76Val" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26749" "I76T" "NC_045512.2:g.227T>C" "YP_009724393.1:p.Ile76Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (19x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26767" "I82T" "NC_045512.2:g.245T>C" "YP_009724393.1:p.Ile82Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (67x overrepresentation vs expected count of ~42 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26767" "I82T" "NC_045512.2:g.245T>C" "YP_009724393.1:p.Ile82Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "homoplasy" "" "" "This mutation presents mainly within the B.1 (44.0%) and B.1.525 (38.1%) lineages. Currently, 99.7% of the B.1.525 lineage isolates carry the M:I82T mutation. While this mutation is scattered across multiple phylogenetic clades, most cases cluster in two recent clades, suggesting a likely selective advantage in certain haplotype backgrounds." "" "" "" "Shen" "2021" "https://doi.org/10.1080/22221751.2021.1922097" "doi:10.1080/22221751.2021.1922097" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26801,26801,26801" "L93L,L93L,L93L" "NC_045512.2:g.279C>G,NC_045512.2:g.279C>A,NC_045512.2:g.279C>T" "YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~628 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26855,26858" "F112F,F112F" "NC_045512.2:g.336C>T,NC_045512.2:g.336C>T" "YP_009724393.1:p.Phe112Phe,YP_009724393.1:p.Phe112Phe" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~463 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26861" "N113N" "NC_045512.2:g.339T>C" "YP_009724393.1:p.Asn113Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (57x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26873" "N117N" "NC_045512.2:g.351C>T" "YP_009724393.1:p.Asn117Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26882,26882" "L120L,L120L" "NC_045512.2:g.360C>A,NC_045512.2:g.360C>T" "YP_009724393.1:p.Leu120Leu,YP_009724393.1:p.Leu120Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26894,26894" "L124L,L124L" "NC_045512.2:g.372C>T,NC_045512.2:g.372C>G" "YP_009724393.1:p.Leu124Leu,YP_009724393.1:p.Leu124Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26895" "H125Y" "NC_045512.2:g.373C>T" "YP_009724393.1:p.His125Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (22x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26895" "H125Y" "NC_045512.2:g.373C>T" "YP_009724393.1:p.His125Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARA_CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26907,26909,26909" "L129L,L129L,L129L" "NC_045512.2:g.385C>T,NC_045512.2:g.387G>A,NC_045512.2:g.387G>T" "YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26927" "E135E" "NC_045512.2:g.405A>G" "YP_009724393.1:p.Glu135Glu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (232x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26951,26951,26951" "V143V,V143V,V143V" "NC_045512.2:g.429G>C,NC_045512.2:g.429G>A,NC_045512.2:g.429G>T" "YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~508 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26966" "H148H" "NC_045512.2:g.444T>C" "YP_009724393.1:p.His148His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26972" "R150R" "NC_045512.2:g.450T>C" "YP_009724393.1:p.Arg150Arg" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~89 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26985" "H155N" "NC_045512.2:g.463C>A" "YP_009724393.1:p.His155Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26987" "H155H" "NC_045512.2:g.465T>C" "YP_009724393.1:p.His155His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27021" "E167Q" "NC_045512.2:g.499G>C" "YP_009724393.1:p.Glu167Gln" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27035,27038" "T172T,T172T" "NC_045512.2:g.516A>G,NC_045512.2:g.516A>G" "YP_009724393.1:p.Thr172Thr,YP_009724393.1:p.Thr172Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27059" "Y179Y" "NC_045512.2:g.537C>T" "YP_009724393.1:p.Tyr179Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27112" "S197T" "NC_045512.2:g.590G>C" "YP_009724393.1:p.Ser197Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (18x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27134" "Y204Y" "NC_045512.2:g.612T>C" "YP_009724393.1:p.Tyr204Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27143" "N207N" "NC_045512.2:g.621C>T" "YP_009724393.1:p.Asn207Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27147" "D209H" "NC_045512.2:g.625G>C" "YP_009724393.1:p.Asp209His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (81x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27367" "Q56X" "NC_045512.2:g.166C>T" "YP_009724394.1:p.Gln56Xaa" "" "open reading frame 6 gene (SARS-CoV-2)" "orf6 gene (SARS-CoV-2)" "open reading frame 6 protein (SARS-CoV-2)" "Orf6 protein (SARS-CoV-2)" "IFN activity" "" "" "The residues listed are determinants of the potent IFN-antagonistic activity of SARS-CoV-2 ORF6 (via blocking mRNA nuclear export)" "" "" "" "Kimura" "2020" "https://doi.org/10.2139/ssrn.3690468" "doi:10.2139/ssrn.3690468" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28144" "L84S" "NC_045512.2:g.251T>C" "YP_009724396.1:p.Leu84Ser" "" "open reading frame 8 gene (SARS-CoV-2)" "orf8 gene (SARS-CoV-2)" "open reading frame 8 protein (SARS-CoV-2)" "Orf8 protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28280" "D3L" "" "YP_009724397.2:p.Asp3Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "subgenomic RNA expression" "" "" "A noncanonical subgenomic RNA which could represent ORF9b is significantly enriched (~16x) in B.1.1.7 SARS-CoV-2 infections, potentially as a result of a triple nucleotide mutation leading to amino acid substitution D3L in nucleocapsid in this lineage which increases complementarity with the genomic leader sequence." "" "" "" "Parker" "2021" "https://doi.org/10.1101/2021.03.02.433156" "doi:10.1101/2021.03.02.433156" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28280" "D3L" "" "YP_009724397.2:p.Asp3Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "At the epitope level, the D3L mutation reduces PIWAS signal in 1.5% of COVID patients (outliers reduce from 2.1% in wild type to 0.5% in mutant). In 3 of these patients (0.5% of the population), that alteration represents the strongest antigen signal and substantially reduces the PIWAS antigen score. In the B1.1.7 lineage this is largely counteracted by the S235F mutation, which increases epitope and antigen scores significantly in two individuals, for a net neutral effect at the population level." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28307,28308,28309,28309,28310,28310,28311,28311" "P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L" "" "YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28307,28308,28309,28309,28310,28310,28311,28311" "P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L" "" "YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13)." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28310" "P13S" "NC_045512.2:g.37C>T" "YP_009724397.2:p.Pro13Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13)." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28310" "P13S" "NC_045512.2:g.37C>T" "YP_009724397.2:p.Pro13Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*27:05." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28769" "T166A" "NC_045512.2:g.496A>G" "YP_009724397.2:p.Thr166Ala" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "Confers a significant PIWAS value decrease (reduced antigenicity)" "" "" "" "Haynes" "2020" "https://doi.org/10.1101/2020.11.23.20235002" "doi:10.1101/2020.11.23.20235002" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28853" "S194T" "NC_045512.2:g.580T>A" "YP_009724397.2:p.Ser194Thr" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28854" "S194L" "NC_045512.2:g.581C>T" "YP_009724397.2:p.Ser194Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "Mutation with a population frequency of 30% in a Mexican dataset, primarily of lineage 20B, but also present in a substantial number of 20A lineage sequences, suggesting convergent evolution." "" "" "" "Barona-Gomez" "2021" "https://doi.org/10.1101/2021.05.18.21256128" "doi:10.1101/2021.05.18.21256128" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28854" "S194L" "NC_045512.2:g.581C>T" "YP_009724397.2:p.Ser194Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In March 2021 this variant had an allele frequency of 47.62 and 7.25% in deceased patients, compared to 35.16 and 3.20% of the same variant in recovered patients, from the Gujarat and global datasets." "" "" "" "Joshi" "2021" "https://doi.org/10.3389/fgene.2021.586569" "doi:10.3389/fgene.2021.586569" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28869" "P199L" "NC_045512.2:g.596C>T" "YP_009724397.2:p.Pro199Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28877,28881" "G204R,G204R" "" "YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "gene expression increase" "" "" "By Western blot, a statistically significant 2x increase in N protein expression in packaging cells was observed using mutant novel virus-like-particles. This did not correlate with luciferase activity (which was not statistically different from D614G wild type)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28879" "S202R" "NC_045512.2:g.606T>G" "YP_009724397.2:p.Ser202Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows major increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881" "R203M" "NC_045512.2:g.608G>T" "YP_009724397.2:p.Arg203Met" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows most increase in RNA content of any N mutation tested, suggesting that this mutation improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881,28877,28881" "R203K,G204R,G204R" "" "YP_009724397.2:p.Arg203Lys,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection in an October 2020 of a 40yo female Brazilian HCW, no hospitalization required in first or second infection. Poor overall genome quality. Genome also has one Spike mutation that would become a defining mutation in lineage P.2, S:p.V1176F" "" "" "" "Amorim" "2021" "https://doi.org/10.3201/eid2706.210558" "doi:10.3201/eid2706.210558" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881,28877,28881" "R203K,G204R,G204R" "" "YP_009724397.2:p.Arg203Lys,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "subgenomic RNA expression" "" "" "This variant shows a significant increase in viral load compared to wild type, but not relative to D614G viruses without the variant in circulating viruses in the Spring of 2020 in Saudia Arabia." "" "" "" "Mourier" "2021" "https://doi.org/10.1101/2021.05.06.21256706" "doi:10.1101/2021.05.06.21256706" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881,28877,28881" "R203K,G204R,G204R" "" "YP_009724397.2:p.Arg203Lys,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "posttranslational modifications" "" "" "This variant, caused by three consecutive SNPs, consistently shows a neighbouring serine 206 (S206) site is highly phosphorylated in the mutant N protein via mass spectrometry." "" "" "" "Mourier" "2021" "https://doi.org/10.1101/2021.05.06.21256706" "doi:10.1101/2021.05.06.21256706" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881,28877,28881" "R203K,G204R,G204R" "" "YP_009724397.2:p.Arg203Lys,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "subgenomic RNA expression" "" "" "This variant, likely arisen by homologous recombination from the core sequence (CS) of the leader transcription-regulating sequence (TRS), generate a novel sub-genomic RNA transcript for the C-terminal dimerization domain. It may also have increased expression of sub-genomic RNA from other open reading frames, based on public data analysis." "" "" "" "Leary" "2021" "https://doi.org/10.1101/2020.04.10.029454" "doi:10.1101/2020.04.10.029454" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881,28877,28881" "R203K,G204R,G204R" "" "YP_009724397.2:p.Arg203Lys,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection in a September 2020 of a 61yo female Brazilian HCW, no hospitalization required in first or second infection. Genome also has one Spike mutation of unknown significance, S:p.Q675H" "" "" "" "Amorim" "2021" "https://doi.org/10.3201/eid2706.210558" "doi:10.3201/eid2706.210558" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881,28877,28881" "R203K,G204R,G204R" "" "YP_009724397.2:p.Arg203Lys,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "subgenomic RNA expression" "" "" "This variant, likely arisen by homologous recombination from the core sequence (CS) of the leader transcription-regulating sequence (TRS), generate a novel sub-genomic RNA transcript for the C-terminal dimerization domain. It may also have increased expression of sub-genomic RNA from other open reading frames, based on public data analysis." "" "" "" "Leary" "2021" "https://doi.org/10.1101/2020.04.10.029454" "doi:10.1101/2020.04.10.029454" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28977" "S235F" "NC_045512.2:g.704C>T" "YP_009724397.2:p.Ser235Phe" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "Substantially increases epitope and antigen scores in 2 of 579 individuals (should increase immune response). In the B1.1.7 lineage this is largely counteracted by the D3L mutation, which decreases PIWAS signal significantly in 1.5% of COVID patients, for a net neutral effect at the population level." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29239,29239" "M322I,M322I" "NC_045512.2:g.966G>A,NC_045512.2:g.966G>T" "YP_009724397.2:p.Met322Ile,YP_009724397.2:p.Met322Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "Agerer" "2021" "https://doi.org/10.1126/sciimmunol.abg6461" "doi:10.1126/sciimmunol.abg6461" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29247" "T325I" "NC_045512.2:g.974C>T" "YP_009724397.2:p.Thr325Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes partial loss of T cell line responsiveness and CTL killing ability by B*40:01-restricted CD8+ N epitope MEVTPSGTWL 322-331." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29247" "T325I" "NC_045512.2:g.974C>T" "YP_009724397.2:p.Thr325Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29266,29266" "L331F,L331F" "NC_045512.2:g.993G>T,NC_045512.2:g.993G>C" "YP_009724397.2:p.Leu331Phe,YP_009724397.2:p.Leu331Phe" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "Agerer" "2021" "https://doi.org/10.1126/sciimmunol.abg6461" "doi:10.1126/sciimmunol.abg6461" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29409" "T379I" "NC_045512.2:g.1136C>T" "YP_009724397.2:p.Thr379Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "335,335" "R24C,R24C" ",NC_045512.2:g.70C>T" "YP_009724389.1:p.Arg24Cys,YP_009724389.1:p.Arg24Cys" "YP_009724389.1:Arg24Cys,YP_009724389.1:Arg24Cys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (25x overrepresentation vs expected count of 514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "347" "V28I" "NC_045512.2:g.82G>A" "YP_009724389.1:p.Val28Ile" "YP_009724389.1:Val28Ile" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (30x overrepresentation vs expected count of 143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "383" "S40P" "NC_045512.2:g.118T>C" "YP_009724389.1:p.Ser40Pro" "YP_009724389.1:Ser40Pro" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~58 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "396" "Q44L" "NC_045512.2:g.131A>T" "YP_009724389.1:p.Gln44Leu" "YP_009724389.1:Gln44Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~19 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "443" "V60I" "NC_045512.2:g.178G>A" "YP_009724389.1:p.Val60Ile" "YP_009724389.1:Val60Ile" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "489" "D75G" "NC_045512.2:g.224A>G" "YP_009724389.1:p.Asp75Gly" "YP_009724389.1:Asp75Gly" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "490,490" "D75E,D75E" "NC_045512.2:g.225T>G,NC_045512.2:g.225T>A" "YP_009724389.1:p.Asp75Glu,YP_009724389.1:p.Asp75Glu" "YP_009724389.1:Asp75Glu,YP_009724389.1:Asp75Glu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~20 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Emergent as 22% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing." "" "" "" "Avanzato" "2020" "https://doi.org/10.1016/j.cell.2020.10.049" "doi:10.1016/j.cell.2020.10.049" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-523) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-517) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 500-523) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,509,518" "M85V,M85V,M85V" "NC_045512.2:g.253A>G,NC_045512.2:g.253A>G,NC_045512.2:g.253A>G" "YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val" "YP_009724389.1:Met85Val,YP_009724389.1:Met85Val,YP_009724389.1:Met85Val" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "508" "H81Q" "NC_045512.2:g.243T>A" "YP_009724389.1:p.His81Gln" "YP_009724389.1:His81Gln" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (30x overrepresentation vs expected count of ~20 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "510" "M85K" "NC_045512.2:g.254T>A" "YP_009724389.1:p.Met85Lys" "YP_009724389.1:Met85Lys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~12 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "561" "R99H" "NC_045512.2:g.296G>A" "YP_009724389.1:p.Arg99His" "YP_009724389.1:Arg99His" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "563" "S100C" "NC_045512.2:g.298A>T" "YP_009724389.1:p.Ser100Cys" "YP_009724389.1:Ser100Cys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (33x overrepresentation vs expected count of ~19 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "592,593" "H110Y,H110Y" ",NC_045512.2:g.328C>T" "YP_009724389.1:p.His110Tyr,YP_009724389.1:p.His110Tyr" "YP_009724389.1:His110Tyr,YP_009724389.1:His110Tyr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (22x overrepresentation vs expected count of ~514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "593" "H110D" "NC_045512.2:g.328C>G" "YP_009724389.1:p.His110Asp" "YP_009724389.1:His110Asp" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~11 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "606" "I114T" "NC_045512.2:g.341T>C" "YP_009724389.1:p.Ile114Thr" "YP_009724389.1:Ile114Thr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (155x overrepresentation vs expected count of ~58 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "657" "A131V" "NC_045512.2:g.392C>T" "YP_009724389.1:p.Ala131Val" "YP_009724389.1:Ala131Val" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "677" "A138T" "NC_045512.2:g.412G>A" "YP_009724389.1:p.Ala138Thr" "YP_009724389.1:Ala138Thr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "761" "S166G" "NC_045512.2:g.496A>G" "YP_009724389.1:p.Ser166Gly" "YP_009724389.1:Ser166Gly" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (132x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "798" "N178S" "NC_045512.2:g.533A>G" "YP_009724389.1:p.Asn178Ser" "YP_009724389.1:Asn178Ser" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" From 9490474d91c57d9c881863b6ee159db0d6fbc564 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 3 Oct 2024 17:02:11 -0700 Subject: [PATCH 049/161] add gene and strand orientation for MPOX, and change unknown publication status from 'false' to empty string --- bin/functional_annotation.py | 26 ++++++++++++++++++++------ 1 file changed, 20 insertions(+), 6 deletions(-) diff --git a/bin/functional_annotation.py b/bin/functional_annotation.py index c5eb494d..57fcc5b0 100755 --- a/bin/functional_annotation.py +++ b/bin/functional_annotation.py @@ -188,7 +188,15 @@ def write_tsv(dframe): # Change the directory # os.chdir(path) - dataFrame_cols = ['organism', 'reference accession', 'reference database name', 'nucleotide position', + if args.accession=='NC_063383.1': # add gene orientation and strand orientation for MPOX + dataFrame_cols = ['organism', 'reference accession', 'reference database name', 'nucleotide position', +'original mutation description', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', +'gene name', 'gene symbol', 'gene orientation', 'strand orientation', 'protein name', 'protein symbol', 'measured variant functional effect', 'inferred variant functional effect', 'viral life cycle functional effect', +'measured variant functional effect description', 'CVX code', 'DrugBank Accession Number', 'Antibody Registry ID', 'author', 'publication year', 'URL', 'DOI', 'PMID', +'peer review status', 'curator', 'mutation functional annotation resource'] + + else: + dataFrame_cols = ['organism', 'reference accession', 'reference database name', 'nucleotide position', 'original mutation description', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', 'gene name', 'gene symbol', 'protein name', 'protein symbol', 'measured variant functional effect', 'inferred variant functional effect', 'viral life cycle functional effect', 'measured variant functional effect description', 'CVX code', 'DrugBank Accession Number', 'Antibody Registry ID', 'author', 'publication year', 'URL', 'DOI', 'PMID', @@ -247,7 +255,7 @@ def write_tsv(dframe): dataFrame["curator"] = "Paul Gordon" ## for now: need to go through # clean up 'peer review status' - dataFrame.loc[dataFrame['peer review status'].isna(), 'peer review status'] = 'false' ##up for debate + dataFrame.loc[dataFrame['peer review status'].isna(), 'peer review status'] = '' ##up for debate dataFrame.loc[dataFrame['peer review status'].str.contains("Journal"), 'peer review status'] = 'true' dataFrame.loc[dataFrame['peer review status'].str.contains("Preprint"), 'peer review status'] = 'false' dataFrame.loc[dataFrame['peer review status'].str.contains("Grey literature"), 'peer review status'] = 'false' ##up for debate @@ -270,17 +278,22 @@ def write_tsv(dframe): for entry in GENE_PROTEIN_POSITIONS_DICT.keys(): # If a gene record matches pokay_id, get 'gene_name' and 'gene_symbol' - if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="gene" and GENE_PROTEIN_POSITIONS_DICT[entry]["gene"]==pokay_id: + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="gene" and ("gene" in GENE_PROTEIN_POSITIONS_DICT[entry].keys()) and GENE_PROTEIN_POSITIONS_DICT[entry]["gene"]==pokay_id: # extract protein names and symbols (ontology) from JSON entry gene_name = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_name"]["label"] gene_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_symbol"]["label"] + gene_orientation = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_orientation"]["label"] + strand_orientation = GENE_PROTEIN_POSITIONS_DICT[entry]["strand_orientation"]["label"] # add gene names and symbols to dataframe dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene name"] = gene_name dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene symbol"] = gene_symbol dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene"] = GENE_PROTEIN_POSITIONS_DICT[entry]["gene"] - + if args.accession=='NC_063383.1': # add gene orientation and strand orientation for MPOX + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene orientation"] = gene_orientation + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "strand orientation"] = strand_orientation + # If a CDS record matches pokay_id, get 'protein_name' and 'protein_symbol' - if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="CDS" and GENE_PROTEIN_POSITIONS_DICT[entry]["gene"]==pokay_id: + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="CDS" and ("gene" in GENE_PROTEIN_POSITIONS_DICT[entry].keys()) and GENE_PROTEIN_POSITIONS_DICT[entry]["gene"]==pokay_id: # extract protein names and symbols (ontology) from JSON entry protein_name = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_name"]["label"] protein_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_symbol"]["label"] @@ -329,7 +342,7 @@ def write_tsv(dframe): mutation_index = mutation_index.rename(columns={"mutation": "original mutation description", 'pos':'nucleotide position', 'hgvs_aa_mutation':'amino acid mutation','hgvs_nt_mutation':'nucleotide mutation', 'hgvs_alias':'amino acid mutation alias', 'gene_symbol':'gene'}) - print("columns", mutation_index.columns) + #print("columns", mutation_index.columns) # remove doubled columns from dataFrame index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias'] dataFrame = dataFrame.drop(columns=index_cols_to_use) @@ -356,6 +369,7 @@ def write_tsv(dframe): # convert nucleotide positions to int format (still str) merged_dataFrame["nucleotide position"] = merged_dataFrame["nucleotide position"].str.replace('.0', '', regex=False) + # create agg dictionary to_list = ['original mutation description', 'nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias'] list_dict = dict.fromkeys(to_list, ','.join) From 76712104cf80756bab561851adc6f0a7c29ac891 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 3 Oct 2024 21:36:12 -0700 Subject: [PATCH 050/161] add MPOX functional annotations in DH template format --- .../NC_063383.1/pokay_annotations_v_0.2.tsv | 7 +++++++ 1 file changed, 7 insertions(+) create mode 100644 assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.2.tsv diff --git a/assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.2.tsv b/assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.2.tsv new file mode 100644 index 00000000..076dd420 --- /dev/null +++ b/assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.2.tsv @@ -0,0 +1,7 @@ +"organism" "reference accession" "reference database name" "nucleotide position" "original mutation description" "nucleotide mutation" "amino acid mutation" "amino acid mutation alias" "gene name" "gene symbol" "gene orientation" "strand orientation" "protein name" "protein symbol" "measured variant functional effect" "inferred variant functional effect" "viral life cycle functional effect" "measured variant functional effect description" "CVX code" "DrugBank Accession Number" "Antibody Registry ID" "author" "publication year" "URL" "DOI" "PMID" "peer review status" "curator" "mutation functional annotation resource" +"Monkeypox virus" "NC_063383.1" "RefSeq" "" "T220A" "" "" "" "" "" "" "" "" "" "drug resistence" "" "" "May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in two site samples (0.44 and 0.49 frequency, culture contaminated and culture negative respectively) from an HIV-positive patient treated with Tecovirimat." "" "" "" "Garrigues" "2023" "" "" "" "unknown" "Paul Gordon" "Pokay" +"Monkeypox virus" "NC_063383.1" "RefSeq" "" "T220I" "" "" "" "" "" "" "" "" "" "drug resistence" "" "" "May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in two site samples (0.44 and 0.49 frequency, culture contaminated and culture negative respectively) from an HIV-positive patient treated with Tecovirimat." "" "" "" "Garrigues" "2023" "" "" "" "unknown" "Paul Gordon" "Pokay" +"Monkeypox virus" "NC_063383.1" "RefSeq" "" "T245I" "" "" "" "" "" "" "" "" "" "drug resistence" "" "" "May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.12 frequency, culture positive with EC50 0.3820uM) from an HIV-positive patient treated with Tecovirimat, may be dragged along by D294V (known from literature) from same sample with 0.91 frequency." "" "" "" "Garrigues" "2023" "" "" "" "unknown" "Paul Gordon" "Pokay" +"Monkeypox virus" "NC_063383.1" "RefSeq" "" "D294V" "" "" "" "" "" "" "" "" "" "drug resistence" "" "" "May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.91 frequency, culture positive with EC50 0.3820uM) from an HIV-positive patient treated with Tecovirimat." "" "" "" "Garrigues" "2023" "" "" "" "unknown" "Paul Gordon" "Pokay" +"Monkeypox virus" "NC_063383.1" "RefSeq" "" "A265D" "" "" "" "" "" "" "" "" "" "drug resistence" "" "" "May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.5 frequency, culture contaminated) from an HIV-positive patient treated with Tecovirimat. Novel T220A also found at similar frequency (0.44) in the same sample, as well as A295E which is known from the literature (0.51 frequency)." "" "" "" "Garrigues" "2023" "" "" "" "unknown" "Paul Gordon" "Pokay" +"Monkeypox virus" "NC_063383.1" "RefSeq" "" "T289A" "" "" "" "" "" "" "" "" "" "drug resistence" "" "" "May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.41 frequency, culture data pending) from an HIV-positive patient treated with Tecovirimat." "" "" "" "Garrigues" "2023" "" "" "" "unknown" "Paul Gordon" "Pokay" From 94a67bbd5bfe9cf47fa4e1e6cfd0ec3047c0a674 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 22 Oct 2024 11:41:43 -0700 Subject: [PATCH 051/161] remove mutation index rows that don't have a nucleotide mutation --- bin/functional_annotation.py | 9 ++++++++- 1 file changed, 8 insertions(+), 1 deletion(-) diff --git a/bin/functional_annotation.py b/bin/functional_annotation.py index 57fcc5b0..617de7ac 100755 --- a/bin/functional_annotation.py +++ b/bin/functional_annotation.py @@ -302,7 +302,9 @@ def write_tsv(dframe): dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "protein symbol"] = protein_symbol # If a mature peptide record matches pokay_id in the 'protein_alias' list, get name of parent, and from there get names and symbols - if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="mature_protein_region_of_CDS" and (pokay_id in GENE_PROTEIN_POSITIONS_DICT[entry]["protein_alias"]): + if (GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="mature_protein_region_of_CDS" or \ + (GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="CDS" and args.accession=='NC_063383.1')) \ + and (pokay_id in GENE_PROTEIN_POSITIONS_DICT[entry]["protein_alias"]): # extract pokay_id, mat_pep, and parent id from JSON entry mat_pep = entry parent = GENE_PROTEIN_POSITIONS_DICT[entry]["Parent"] @@ -343,6 +345,11 @@ def write_tsv(dframe): 'hgvs_aa_mutation':'amino acid mutation','hgvs_nt_mutation':'nucleotide mutation', 'hgvs_alias':'amino acid mutation alias', 'gene_symbol':'gene'}) #print("columns", mutation_index.columns) + # remove index columns that don't have a nucleotide mutation entry + initial_length = mutation_index.shape[0] + mutation_index = mutation_index[mutation_index['nucleotide mutation'].notna()] + after_length = mutation_index.shape[0] + print("Removed " + str(initial_length - after_length) + "/" + str(after_length) + " mutation index rows that are missing a nucleotide mutation") # remove doubled columns from dataFrame index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias'] dataFrame = dataFrame.drop(columns=index_cols_to_use) From 02ad2e14b8b189b1a1bf935f72118625ab0a4eb6 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 22 Oct 2024 11:42:06 -0700 Subject: [PATCH 052/161] use pd.explode() in unnest_multi() --- bin/functions.py | 13 ++++++++++++- 1 file changed, 12 insertions(+), 1 deletion(-) diff --git a/bin/functions.py b/bin/functions.py index 5051c39e..cbe3c65a 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -272,15 +272,26 @@ def unnest_multi(df, columns, reset_index=False): # all the lists must be the same length across columns in a given row, but # can vary between rows # adapted from https://stackoverflow.com/questions/21160134/flatten-a-column-with-value-of-type-list-while-duplicating-the-other-columns-va + ''' df_flat = pd.DataFrame(columns=columns) + print("df_flat") + print(df_flat[df_flat.index.duplicated()]) + print("") for col in columns: col_flat = pd.DataFrame([[i, x] for i, y in df[col].apply(list).iteritems() for x in y], columns=['I', col]) - col_flat = col_flat.set_index('I') + print("whole col flat") + print(col_flat) + #col_flat = col_flat.set_index('I') + print("") + print("col_flat duplications") + print(col_flat[col_flat.index.duplicated()]) df_flat[col] = col_flat df = df.drop(labels=columns, axis=1) df = df.merge(df_flat, left_index=True, right_index=True) + ''' + df = df.explode(columns, ignore_index=False) if reset_index: df = df.reset_index(drop=True) return df From 48d068f38265ed47085ac2356868d041bb33c0b3 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 22 Oct 2024 11:42:58 -0700 Subject: [PATCH 053/161] workaround unmatched list lengths to work with pd.explode() --- ...splitmutationnames_functionalannotation.py | 43 ++++++++++++++++--- 1 file changed, 37 insertions(+), 6 deletions(-) diff --git a/bin/splitmutationnames_functionalannotation.py b/bin/splitmutationnames_functionalannotation.py index 68c6c1e1..eebcd313 100755 --- a/bin/splitmutationnames_functionalannotation.py +++ b/bin/splitmutationnames_functionalannotation.py @@ -44,9 +44,9 @@ def parse_args(): dataFrame_cols = ['organism', 'reference accession', 'reference database name', 'nucleotide position', 'original mutation description', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', 'comb_mutation', -'gene name', 'gene symbol', 'protein name', 'protein symbol', 'variant functional effect', -'variant functional effect description', 'author', 'publication year', 'URL', 'DOI', 'PMID', -'peer review status', 'curator', 'mutation functional annotation resource'] +'gene name', 'gene symbol', 'protein name', 'protein symbol', 'measured variant functional effect', +'inferred variant functional effect', 'viral life cycle functional effect', 'measured variant functional effect description', +'author', 'publication year', 'URL', 'DOI', 'PMID', 'peer review status', 'curator', 'mutation functional annotation resource'] # split names in functional annotations file @@ -55,15 +55,46 @@ def parse_args(): # remove any leading/trailing spaces for column in df.columns: df[column] = df[column].astype(str).str.strip() - + # create "comb_mutation" column with the lists from 'original mutation description' df['comb_mutation'] = df['original mutation description'] # unnest all these columns to_unnest = ['original mutation description', 'nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias'] + df['amino acid mutation alias'] = df['amino acid mutation alias'].replace('nan', np.nan, regex=False) + for column in to_unnest: - df[column] = df[column].str.replace('nan', '') - df[column] = df[column].str.split(',') + # convert not-null values to lists + df.loc[df[column].notna(), column] = df[column].astype(str).str.split(',') + #convert null values to empty lists + df.loc[df[column].isnull(),[column]] = df.loc[df[column].isnull(),column].apply(lambda x: []) + # make temporary column for lengths of lists + len_count = column + ' length' + df.loc[df[column].notna(), len_count] = df[column].str.len() + + # make sure all columns have the same number of elements; if they don't, throw an error + if not (df['original mutation description length'].equals(df['nucleotide position length'])): + print("Original mutation description and nucleotide position columns are of unequal length") + if not (df['nucleotide mutation length'].equals(df['nucleotide position length'])): + print("Nucleotide mutation and nucleotide position columns are of unequal length") + if not (df['amino acid mutation length'].equals(df['nucleotide position length'])): + print("Amino acid mutation and nucleotide position columns are of unequal length") + if not (df['amino acid mutation alias length'].equals(df['nucleotide position length'])): + print("Amino acid mutation alias and nucleotide position columns are of unequal length") + # this is only column that SHOULD have an issue, so the solution is hardcoded here: + # calculate how many elements to add to each list + df['to_add'] = df['nucleotide position length'] - df['amino acid mutation alias length'] + # convert columns to lists of lists + A_list = df['amino acid mutation alias'].tolist() # column that needs padding with NaNs, represented as a nested list + add_list = df['to_add'].tolist() # list of integers representing how many elements to add to each list + na_list = [np.nan]*len(add_list) # flat list of NaNs + # create new list padded with NaNs + nas_to_add_list = [[a]*b for a,b in zip(na_list, add_list)] # nested list of NaNs to add + padded_list = [a + b for a,b in zip(A_list, nas_to_add_list)] # column to explode padded with NaNs + # add padded column to df + df['amino acid mutation alias'] = padded_list + + # explode list columns df = unnest_multi(df, to_unnest, reset_index=True) # keep only unique names in 'comb_mutation', no repeats From dc7932d10d0a4853d299ff50f2ae608045380448 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 22 Oct 2024 17:38:25 -0700 Subject: [PATCH 054/161] Adapt vcf2gvf to new JSON keys --- bin/functions.py | 45 +++++++++++++++++++++++++++++++++------------ bin/vcf2gvf.py | 11 +++++++---- 2 files changed, 40 insertions(+), 16 deletions(-) diff --git a/bin/functions.py b/bin/functions.py index cbe3c65a..2faf02e3 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -3,8 +3,9 @@ import logging # standard variables used by all scripts -empty_attributes = 'ID=;Name=;alias=;gene_name=;gene_symbol=;protein_name=;protein_symbol=;\ - protein_id=;alias_protein_id=;transcript_id=;ps_filter=;ps_exc=; \ +empty_attributes = 'ID=;Name=;alias=;gene=;gene_name=;gene_symbol=;product=; \ + protein_alias=;protein_name=;protein_symbol=;\ + protein_id=;alias_protein_id=;locus_tag=;ps_filter=;ps_exc=; \ mat_pep=;mat_pep_desc=;mat_pep_acc=;ro=;ao=;dp=;sample_size=; \ Reference_seq=;Variant_seq=;nt_name=;aa_name=;hgvs_nt=;hgvs_aa=;hgvs_alias=; \ vcf_gene=;mutation_type=;viral_lineage=;multi_aa_name=; \ @@ -12,6 +13,7 @@ citation=;comb_mutation=;function_description=;heterozygosity=; \ clade_defining=;variant=;variant_type=;voi_designation_date=; \ voc_designation_date=;vum_designation_date=;status=;' + empty_attributes = empty_attributes.replace(" ", "") gvf_columns = ['#seqid', '#source', '#type', '#start', '#end', @@ -89,20 +91,20 @@ def add_hgvs_names(new_gvf): #df.loc[mask, 'val'] = df.loc[mask, 'val'].apply(f) # add hgvs nt snp names nt_snp_mask = new_gvf['nt_name'].str.contains(nt_snp_regex, regex=True) - new_gvf.loc[nt_snp_mask, 'hgvs_nt'] = new_gvf['#seqid'] + "(" + new_gvf['transcript_id'] + "):" + \ + new_gvf.loc[nt_snp_mask, 'hgvs_nt'] = new_gvf['#seqid'] + "(" + new_gvf['locus_tag'] + "):" + \ new_gvf.loc[nt_snp_mask, 'nt_name'].apply(rewrite_nt_snps_as_hgvs) # add hgvs nt dels and dups nt_del_dup_mask = new_gvf['nt_name'].str.contains(nt_del_dup_regex, regex=True) - new_gvf.loc[nt_del_dup_mask,'hgvs_nt'] = new_gvf['#seqid'] + "(" + new_gvf['transcript_id'] + "):" + \ + new_gvf.loc[nt_del_dup_mask,'hgvs_nt'] = new_gvf['#seqid'] + "(" + new_gvf['locus_tag'] + "):" + \ new_gvf.loc[nt_del_dup_mask, 'nt_name'].apply(remove_nts_from_nt_name) # add hgvs nt ins nt_ins_mask = new_gvf['nt_name'].str.contains(nt_ins_regex, regex=True) - new_gvf.loc[nt_ins_mask, 'hgvs_nt'] = new_gvf['#seqid'] + "(" + new_gvf['transcript_id'] + "):" + new_gvf['nt_name'] + new_gvf.loc[nt_ins_mask, 'hgvs_nt'] = new_gvf['#seqid'] + "(" + new_gvf['locus_tag'] + "):" + new_gvf['nt_name'] # add hgvs nt delins: change to eg. g.123_129delinsAC nt_delins_mask = new_gvf['nt_name'].str.contains(nt_delins_regex, regex=True) - #new_gvf.loc[nt_delins_mask, 'hgvs_nt'] = new_gvf['#seqid'] + "(" + new_gvf['transcript_id'] + "):" + "TBA!" #new_gvf['nt_name'] + #new_gvf.loc[nt_delins_mask, 'hgvs_nt'] = new_gvf['#seqid'] + "(" + new_gvf['locus_tag'] + "):" + "TBA!" #new_gvf['nt_name'] - # remove transcript id in parentheses for all HGVS nucleotide names where 'transcript_id'=='n/a' + # remove transcript id in parentheses for all HGVS nucleotide names where 'locus_tag'=='n/a' new_gvf['hgvs_nt'] = new_gvf['hgvs_nt'].str.replace("(n/a)", "", regex=False) # define aa regex patterns @@ -506,25 +508,44 @@ def map_pos_to_gene_protein(pos, GENE_PROTEIN_POSITIONS_DICT): # loop through all CDS regions in dict to get attributes for entry in GENE_PROTEIN_POSITIONS_DICT.keys(): - if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="CDS" and ("protein_alias" in GENE_PROTEIN_POSITIONS_DICT[entry].keys()): + + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="CDS" and ("protein_alias" in GENE_PROTEIN_POSITIONS_DICT[entry]): + # extract values from JSON entry start = GENE_PROTEIN_POSITIONS_DICT[entry]["start"] end = GENE_PROTEIN_POSITIONS_DICT[entry]["end"] #aa_start = GENE_PROTEIN_POSITIONS_DICT[entry]["aa_start"] #aa_end = GENE_PROTEIN_POSITIONS_DICT[entry]["aa_end"] gene = GENE_PROTEIN_POSITIONS_DICT[entry]["gene"] - protein_name = GENE_PROTEIN_POSITIONS_DICT[entry]["product"] - protein_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_alias"] + product = GENE_PROTEIN_POSITIONS_DICT[entry]["product"] + protein_alias = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_alias"] + protein_name = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_name"]["label"] + protein_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_symbol"]["label"] protein_id = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_id"] - transcript_id = GENE_PROTEIN_POSITIONS_DICT[entry]["locus_tag"] + locus_tag = GENE_PROTEIN_POSITIONS_DICT[entry]["locus_tag"] # fill in attributes for mutations in this CDS region cds_mask = df[pos_column].astype(int).between(start, end, inclusive="both") df.loc[cds_mask, "gene"] = gene + df.loc[cds_mask, "product"] = product + df.loc[cds_mask, "protein_alias"] = ','.join(protein_alias) df.loc[cds_mask, "protein_name"] = protein_name df.loc[cds_mask, "protein_symbol"] = protein_symbol df.loc[cds_mask, "protein_id"] = protein_id - df.loc[cds_mask, "transcript_id"] = transcript_id + df.loc[cds_mask, "locus_tag"] = locus_tag + + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="gene": + + # extract values from JSON entry + start = GENE_PROTEIN_POSITIONS_DICT[entry]["start"] + end = GENE_PROTEIN_POSITIONS_DICT[entry]["end"] + gene_name = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_name"]["label"] + gene_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_symbol"]["label"] + + # fill in attributes for mutations in this gene region + gene_mask = df[pos_column].astype(int).between(start, end, inclusive="both") + df.loc[gene_mask, "gene_name"] = gene_name + df.loc[gene_mask, "gene_symbol"] = gene_symbol # label all mutations that didn't belong to any gene as "intergenic" df.loc[df["gene"].isna(), "gene"] = "intergenic" diff --git a/bin/vcf2gvf.py b/bin/vcf2gvf.py index 2a65f795..8f43e4d1 100755 --- a/bin/vcf2gvf.py +++ b/bin/vcf2gvf.py @@ -11,7 +11,7 @@ ['ID', 'Name', 'gene_name', 'gene_symbol', 'protein_name', 'protein_symbol', 'protein_id', 'ps_filter', 'ps_exc', 'mat_pep', 'mat_pep_desc','mat_pep_acc', 'ro', 'ao', 'dp', 'sample_size', 'Reference_seq', 'Variant_seq', 'nt_name', 'aa_name', 'hgvs_nt', 'hgvs_aa', 'hgvs_alias', 'vcf_gene', 'mutation_type', -'viral_lineage', 'alternate_frequency', 'transcript_id'] +'viral_lineage', 'alternate_frequency', 'locus_tag'] """ import argparse @@ -83,12 +83,15 @@ def vcftogvf(vcf, strain, GENE_PROTEIN_POSITIONS_DICT, sample_size): # add gene and protein attributes from JSON json_df = map_pos_to_gene_protein( vcf_df['POS'].astype(int), GENE_PROTEIN_POSITIONS_DICT) - new_gvf["gene_name"] = json_df["gene"] - new_gvf["gene_symbol"] = json_df["gene"] + new_gvf["gene"] = json_df["gene"] + new_gvf["gene_name"] = json_df["gene_name"] + new_gvf["gene_symbol"] = json_df["gene_symbol"] + new_gvf["product"] = json_df["product"] + new_gvf["protein_alias"] = json_df["protein_alias"] new_gvf["protein_name"] = json_df["protein_name"] new_gvf["protein_symbol"] = json_df["protein_symbol"] new_gvf["protein_id"] = json_df["protein_id"] - new_gvf["transcript_id"] = json_df["transcript_id"] + new_gvf["locus_tag"] = json_df["locus_tag"] new_gvf["alias_protein_id"] = 'n/a' # add 'alias' column for ORF1a/b mutations, and fill in "alias_protein_id" for these as well From 2734f7cbd461c1fa92f419b0b81aa56ad7615a52 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 00:35:04 -0700 Subject: [PATCH 055/161] align attribute keys with DH template --- bin/vcf2gvf.py | 4 ++-- 1 file changed, 2 insertions(+), 2 deletions(-) diff --git a/bin/vcf2gvf.py b/bin/vcf2gvf.py index 8f43e4d1..649f3a76 100755 --- a/bin/vcf2gvf.py +++ b/bin/vcf2gvf.py @@ -76,7 +76,7 @@ def vcftogvf(vcf, strain, GENE_PROTEIN_POSITIONS_DICT, sample_size): # add other attributes new_gvf['sample_size'] = sample_size - new_gvf['Name'] = vcf_df["Names"] + new_gvf['original_mutation_description'] = vcf_df["Names"] new_gvf['viral_lineage'] = strain new_gvf['alternate_frequency'] = vcf_df["AF"] @@ -109,7 +109,7 @@ def vcftogvf(vcf, strain, GENE_PROTEIN_POSITIONS_DICT, sample_size): # add 'ID' attribute: here, rows with the same entry in 'Name' # get the same ID (should all be different) - new_gvf['ID'] = 'ID_' + new_gvf.groupby('Name', sort=False).ngroup().astype(str) + new_gvf['ID'] = 'ID_' + new_gvf.groupby('original_mutation_description', sort=False).ngroup().astype(str) # merge attributes back into a single column new_gvf = rejoin_attributes(new_gvf, empty_attributes) From 8f415b5b16298872dbdcc84434374fab59e0d2cb Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 00:36:28 -0700 Subject: [PATCH 056/161] align attribute keys with DH template --- bin/functions.py | 17 +++++++++-------- 1 file changed, 9 insertions(+), 8 deletions(-) diff --git a/bin/functions.py b/bin/functions.py index 2faf02e3..c7d18063 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -3,14 +3,15 @@ import logging # standard variables used by all scripts -empty_attributes = 'ID=;Name=;alias=;gene=;gene_name=;gene_symbol=;product=; \ +empty_attributes = 'ID=;original_mutation_description=;alias=;gene=;gene_name=;gene_symbol=;product=; \ protein_alias=;protein_name=;protein_symbol=;\ protein_id=;alias_protein_id=;locus_tag=;ps_filter=;ps_exc=; \ mat_pep=;mat_pep_desc=;mat_pep_acc=;ro=;ao=;dp=;sample_size=; \ Reference_seq=;Variant_seq=;nt_name=;aa_name=;hgvs_nt=;hgvs_aa=;hgvs_alias=; \ vcf_gene=;mutation_type=;viral_lineage=;multi_aa_name=; \ - multiaa_comb_mutation=;alternate_frequency=;function_category=;source=; \ - citation=;comb_mutation=;function_description=;heterozygosity=; \ + multiaa_comb_mutation=;alternate_frequency=;measured_variant_functional_effect=;inferred_variant_functional_effect=; \ + viral_life_cycle_functional_effect=;URL=; \ + citation=;comb_mutation=;measured_variant_functional_effect_description=;heterozygosity=; \ clade_defining=;variant=;variant_type=;voi_designation_date=; \ voc_designation_date=;vum_designation_date=;status=;' @@ -582,13 +583,13 @@ def add_alias_names(df, GENE_PROTEIN_POSITIONS_DICT): # split up all names in alias_mask into letter-number-letter columns # hacky workaround to fix later: in rows that begin with a number, add "PLACEHOLDER" to the front before splitting them up, to stop NaNs - df.loc[df['Name'].str[0].str.isdigit(), 'Name'] = "PLACEHOLDER" + df['Name'].astype(str) + df.loc[df['original_mutation_description'].str[0].str.isdigit(), 'original_mutation_description'] = "PLACEHOLDER" + df['original_mutation_description'].astype(str) # split at underscores - if df['Name'].str.contains("_").any(): - df[['mutation_1', 'mutation_2']] = df['Name'].str.split('_', expand=True) + if df['original_mutation_description'].str.contains("_").any(): + df[['mutation_1', 'mutation_2']] = df['original_mutation_description'].str.split('_', expand=True) else: - df['mutation_1'] = df['Name'] + df['mutation_1'] = df['original_mutation_description'] df['mutation_2'] = None df[['1_start', '1_num', '1_end']] = df['mutation_1'].str.extract('([A-Za-z]+)(\\d+\\.?\\d*)([A-Za-z]*)', expand=True) @@ -618,7 +619,7 @@ def add_alias_names(df, GENE_PROTEIN_POSITIONS_DICT): df.loc[alias_mask, 'alias'] = df['1_alias'].astype(str) + '_' + df['2_alias'].astype(str) # remove the placeholder - df['Name'] = df['Name'].str.replace("PLACEHOLDER","") + df['original_mutation_description'] = df['original_mutation_description'].str.replace("PLACEHOLDER","") df['alias'] = df['alias'].str.replace("PLACEHOLDER","") # remove nans From 3bbe34d6326912087c37bee836a5cdcbe56d42ed Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 00:36:48 -0700 Subject: [PATCH 057/161] adapt to new JSON keys --- bin/addfunctions2gvf.py | 40 ++++++++++++++++++++++------------------ 1 file changed, 22 insertions(+), 18 deletions(-) diff --git a/bin/addfunctions2gvf.py b/bin/addfunctions2gvf.py index 7cf4d2a9..b712532f 100755 --- a/bin/addfunctions2gvf.py +++ b/bin/addfunctions2gvf.py @@ -8,7 +8,7 @@ This script annotates GVF files with the functional annotation. The attributes completed by this script are: -["function_category", "function_description", "source", +["measured_variant_functional_effect", "measured_variant_functional_effect_description", "source", "citation", "comb_mutation"] """ @@ -44,26 +44,30 @@ def add_pokay_annotations(gvf, annotation_file): gvf = separate_attributes(gvf) # drop columns that are going to be re-added in the merge - functional_attributes = ["function_category", "function_description", - "source", "citation", "comb_mutation"] + functional_attributes = ["measured_variant_functional_effect", "measured_variant_functional_effect_description", + "URL", "citation"] #"comb_mutation" gvf = gvf.drop(columns=functional_attributes) # load functional annotations spreadsheet df = pd.read_csv(annotation_file, sep='\t', header=0) + # replace spaces in column names with underscores to match the gvf attributes + pokay_columns = df.columns.tolist() + underscore_columns = [col.replace(" ", "_") for col in pokay_columns] + rename_dict = dict(zip(pokay_columns, underscore_columns)) + df = df.rename(columns=rename_dict) + # if no author, fill with "UNKNOWN" df['author'] = df['author'].fillna('UNKNOWN') # remove any leading/trailing spaces for column in df.columns: df[column] = df[column].fillna('') df[column] = df[column].astype(str).str.strip() - # merge annotated vcf and functional annotation files by 'Name' and 'protein_symbol' - df = df.rename(columns={"original mutation description": "Name", 'variant functional effect':"function_category", \ - 'variant functional effect description':"function_description", 'URL':"source", 'protein symbol':'protein_symbol'}) - df['citation'] = df['author'] + ' et al. (' + df['publication year'].str.replace(".0", "", regex=False) + ')' - df_columns = functional_attributes + ["Name", "protein_symbol"] + # merge annotated vcf and functional annotation files by 'original_mutation_description' and 'protein_symbol' + df['citation'] = df['author'] + ' et al. (' + df['publication_year'].str.replace(".0", "", regex=False) + ')' + df_columns = functional_attributes + ["original_mutation_description", "protein_symbol"] df = df[df_columns] - merged_df = pd.merge(gvf, df, on=['Name', 'protein_symbol'], how='left') #, 'alias' + merged_df = pd.merge(gvf, df, on=['original_mutation_description', 'protein_symbol'], how='left') #, 'alias' # data cleaning merged_df['comb_mutation'] = merged_df['comb_mutation'].str.replace( @@ -76,7 +80,7 @@ def add_pokay_annotations(gvf, annotation_file): # join columns with commas in between merged_df["mutation_group"] = \ - merged_df["Name"].astype(str) + "," + \ + merged_df["original_mutation_description"].astype(str) + "," + \ merged_df["comb_mutation"].astype(str) + "," + \ merged_df['multiaa_comb_mutation'].astype(str) # cleaning: remove nans, quotations marks, spaces @@ -101,12 +105,12 @@ def add_pokay_annotations(gvf, annotation_file): merged_df["mutation_group"] = pd.Series(sorted_group_list) # make another column to check if all members of the group are - # represented individually in 'Name' (True/False) - unique_Name_entries = set(merged_df['Name'].tolist()) - group_fully_represented = [set(x).issubset(unique_Name_entries) + # represented individually in 'original_mutation_description' (True/False) + unique_original_mutation_description_entries = set(merged_df['original_mutation_description'].tolist()) + group_fully_represented = [set(x).issubset(unique_original_mutation_description_entries) for x in nested_list] merged_df['group_fully_represented'] = group_fully_represented - # drop rows with mutation group members not found in 'Name', + # drop rows with mutation group members not found in 'original_mutation_description', # leaving the index unchanged merged_df = merged_df[merged_df['group_fully_represented']==True] @@ -116,8 +120,8 @@ def add_pokay_annotations(gvf, annotation_file): 'mutation_group', sort=False).ngroup().astype(str) # change semicolons in function descriptions to colons - merged_df['function_description'] = merged_df[ - 'function_description'].str.replace(';', ':') + merged_df['measured_variant_functional_effect_description'] = merged_df[ + 'measured_variant_functional_effect_description'].str.replace(';', ':') # replace NaNs in df with empty string merged_df = merged_df.fillna('') @@ -158,9 +162,9 @@ def add_pokay_annotations(gvf, annotation_file): # functional_annotations) to a .tsv file # create mask to find which rows do not have a functional annotation - notinPokay_mask = pokay_annotated_gvf["#attributes"].str.contains("function_category=;") + notinPokay_mask = pokay_annotated_gvf["#attributes"].str.contains("measured_variant_functional_effect=;") # extract all mutation names from #attributes column - names = pd.Series(pokay_annotated_gvf["#attributes"].str.findall('(?<=Name=)(.*?)(?=;)').str[0]) + names = pd.Series(pokay_annotated_gvf["#attributes"].str.findall('(?<=original_mutation_description=)(.*?)(?=;)').str[0]) # get unique mutation names not in Pokay unmatched_names = pd.Series(names[notinPokay_mask].unique()) # save unmatched names to file From 8b6307c0ebe5a0bbd4172861ef1931da6cbeeea6 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 00:56:32 -0700 Subject: [PATCH 058/161] archive copy of gvf2tsv.py --- bin/archive/gvf2tsv.py | 487 +++++++++++++++++++++++++++++++++++++++++ 1 file changed, 487 insertions(+) create mode 100755 bin/archive/gvf2tsv.py diff --git a/bin/archive/gvf2tsv.py b/bin/archive/gvf2tsv.py new file mode 100755 index 00000000..bf4f846d --- /dev/null +++ b/bin/archive/gvf2tsv.py @@ -0,0 +1,487 @@ +#!/usr/bin/env python +# -*- coding: utf-8 -*- +""" +Created on Mon Aug 9 10:47:11 2021 + +@authors: madeline & zohaib + +This script converts GVF files to TSVs, for later conversion to a PDF +case report. + +""" +import argparse +import pandas as pd +import os +import re +from functions import separate_attributes + + +def parse_args(): + parser = argparse.ArgumentParser( + description='Converts GVF files to a TSV report') + parser.add_argument('--gvf_files', type=str, default=None, + nargs='*', help='Paths to GVF files to process') + parser.add_argument('--clades', type=str, default=None, + help='TSV file of WHO strain names and ' + 'VOC/VOI status') + parser.add_argument('--outtsv', type=str, + default="surveillance_report.tsv", + help='Filepath for finished .tsv') + group = parser.add_mutually_exclusive_group() + group.add_argument('--specify_variants', type=str, default=None, + nargs='*', help='Name(s) of WHO variant(s) to ' + 'make report for. Not ' + 'case-sensitive. Space separated.') + group.add_argument('--all_variants', action="store_true", + help='Create reports for all variants, ' + 'using all available reference lineage ' + 'gvf files. Not case-sensitive.') + parser.add_argument('--table', type=str, default=None, + help='Multi-strain TSV file generated in ' + 'workflow that contains num_seqs column') + parser.add_argument('--user', action="store_true", + help='Use user-uploaded file') + + return parser.parse_args() + + +def match_gvfs_to_who_variant(pango_lineage_list, gvf_files_list): + matched_files = [] + if len(pango_lineage_list) > 1: + for lineage in pango_lineage_list: + if "*" in lineage: + lineage = lineage.replace("*", "") + matched_files.extend([i for i in gvf_files_list if + i.startswith(lineage)]) + + matched_files = sorted(set(matched_files)) + else: + for lineage in pango_lineage_list: + # matched_files.extend([i for i in gvf_files_list if + # i.startswith(lineage)]) + matched_files = ([i for i in gvf_files_list if + i[:i.find("_")]==lineage]) + + return matched_files + + +def find_variant_pop_size(table, pango_lineage_list): + strain_tsv_df = pd.read_csv(table, header=0, + delim_whitespace=True, thousands=r',', + usecols=['file', 'num_seqs']) + + files = match_gvfs_to_who_variant( + pango_lineage_list=pango_lineage_list, + gvf_files_list=strain_tsv_df['file'].tolist()) + # print(files) + + pop_size = strain_tsv_df.loc[strain_tsv_df['file'].isin( + files), 'num_seqs'].sum() + return pop_size + + +def add_ao_by_variant_seq(ao_str, variant_seq_str): + """ + Takes a pair of strings like ao_str="7,7,24" and + variant_seq_str="T,T,T" or "8,21,3" and "T,T,A". + Output should be a string "T=38" (first case) or "T=29, A=3" ( + second case). + """ + ao_list = ao_str.split(',') + ao_list = [int(x) for x in ao_list] + var_str_list = variant_seq_str.split(',') + zipped_lists = list(zip(var_str_list, ao_list)) + + ao_dict = dict() + for pair in zipped_lists: + # if a variant seq isn't in the dictionary, add it + if pair[0] not in ao_dict: + ao_dict[pair[0]] = pair[1] + # if it's already there, add this ao to the existing key + else: + ao_dict[pair[0]] += pair[1] + + # create 3 strings: one for ao, one for var_seq, one for both + # joined together with an '=' between + joined_string = '' + ao_string = '' + var_string = '' + for item in list(ao_dict.items()): + joined_string = joined_string + item[0] + '=' + str(item[1]) \ + + ', ' + ao_string = ao_string + str(item[1]) + ',' + var_string = var_string + item[0] + ',' + joined_string = joined_string.rstrip(", ") + ao_string = ao_string.rstrip(", ") + var_string = var_string.rstrip(", ") + + return joined_string, ao_string, var_string + + +def add_one_from_each_lineage(count_str, lineage_str, mode): + """ + Takes a pair of strings like count_str="7,7,24" and + lineage_str="Q.3,Q.3,Q.1". + Output should be a string "31", adding unique lineage + values only, if mode='add'. + If mode='comma', returns a comma-separated set of values, + like "7,24". + """ + count_list = count_str.split(';') + if mode == 'add': + count_list = [int(x) for x in count_list] + lineage_str_list = lineage_str.replace(" ", "") + lineage_str_list = lineage_str.split(',') + zipped_lists = list(zip(lineage_str_list, count_list)) + + count_dict = dict() + for pair in zipped_lists: + # if a lineage isn't in the dictionary, add it + if pair[0] not in count_dict: + count_dict[pair[0]] = pair[1] + # if it's already there, do nothing + + # if mode=='comma', return a comma-separated string of values + if mode == 'comma': + return_str = ','.join(list(count_dict.values())) + # elif mode=='add', add up all the keys and return the value as a + # string + elif mode == 'add': + return_str = str(sum(list(count_dict.values()))) + + return return_str + + +def gvf2tsv(gvf): + # read in gvf + gvf_columns = ['#seqid', '#source', '#type', '#start', '#end', + '#score', '#strand', '#phase', '#attributes'] + + df = pd.read_csv(gvf, sep='\t', names=gvf_columns) + # remove pragmas and original header + df = df[~df['#seqid'].str.contains("#")] + # restart index from 0 + df = df.reset_index(drop=True) + + # expand #attributes column into multiple columns for each attribute, + # keeping the original #attributes column + df = separate_attributes(df) + # change all labels to lowercase + df.columns = [x.lower() for x in df.columns] + # drop original #attributes column, and also #source + df = df.drop(labels=['#source', '#attributes'], axis=1) + + # remove '#' from column names + df.columns = df.columns.str.replace("#", "") + + # drop unwanted columns + df = df.drop(labels=['seqid', 'type', 'end', + 'strand', 'score', 'phase', 'id'], axis=1) + + # rename 'dp' column to 'sequence_depth', make 'viral_lineage' + # plural + df = df.rename(columns={'sample_size': 'obs_sample_size', + 'viral_lineage': 'viral_lineages', + 'source': 'citation_url'}) + + return df + + +def streamline_user(tsv_df): + tsv_df = tsv_df.rename(columns={'multiaa_comb_mutation': + 'multiaa_mutation_split_names'}) + cols = ['name', 'nt_name', 'aa_name', 'multi_aa_name', + 'multiaa_mutation_split_names', 'start', 'vcf_gene', + 'chrom_region', 'mutation_type', 'dp', 'obs_sample_size', + 'ps_filter', 'ps_exc', 'mat_pep_id', + 'mat_pep_desc', 'mat_pep_acc', 'ro', 'ao', + 'variant_seq', 'reference_seq', 'function_category', + 'citation', 'citation_url', 'comb_mutation', + 'function_description', + 'heterozygosity'] + tsv_df = tsv_df[cols] + + return tsv_df + + +def streamline_tsv(tsv_df): + # find identical rows across strains, and keep only one row. + # change n/a to 0 in 'ao' for counting purposes + tsv_df['ao'] = tsv_df['ao'].str.replace("n/a", "0") + + ''' + # make ro, dp, and obs_sample_size numeric + for colname in ['ro', 'dp', 'obs_sample_size']: + tsv_df[colname] = pd.to_numeric(tsv_df[colname], + errors='coerce') + ''' + # make obs_sample_size numeric + tsv_df['obs_sample_size'] = pd.to_numeric(tsv_df['obs_sample_size'], + errors='coerce') + + agg_dict = dict((col, 'first') for col in + tsv_df.columns.values.tolist()) + + agg_dict['obs_sample_size'] = 'sum' + # join some columns with commas + agg_dict['viral_lineages'] = ', '.join + agg_dict['clade_defining'] = ','.join + agg_dict['ao'] = ';'.join + agg_dict['dp'] = ';'.join + agg_dict['ro'] = ';'.join + agg_dict['variant_seq'] = ','.join + + cols_to_check = ['name', 'nt_name', 'aa_name', 'multi_aa_name', + 'multiaa_comb_mutation', 'start', + 'function_category', 'citation', + 'comb_mutation', 'function_description', + 'heterozygosity'] + + final_df = tsv_df.groupby(cols_to_check).agg(agg_dict) + final_df = final_df.rename(columns={'ao': 'ao_all', + 'variant_seq': + 'variant_seq_all', + 'multiaa_comb_mutation': + 'multiaa_mutation_split_names'}) + + # add dp, ro per mutation + for colname in ['dp', 'ro']: + final_df[colname] = [add_one_from_each_lineage(x, y, mode='add') + for x, y in + zip(final_df[colname], + final_df['viral_lineages'])] + + # add ao, variant_seq per mutation + for colname in ['ao_all', 'variant_seq_all']: + final_df[colname] = [ + add_one_from_each_lineage(x, y, mode='comma') for x, y in + zip(final_df[colname], + final_df['viral_lineages'])] + + # add ao according to the heterogeneous mutations + final_df['ao_by_var_seq'] = [add_ao_by_variant_seq(x, y)[0] for x, y + in zip(final_df['ao_all'], + final_df['variant_seq_all'])] + final_df['ao'] = [add_ao_by_variant_seq(x, y)[1] for x, y in + zip(final_df['ao_all'], + final_df['variant_seq_all'])] + final_df['variant_seq'] = [add_ao_by_variant_seq(x, y)[2] for x, y + in zip(final_df['ao_all'], + final_df['variant_seq_all'])] + + # remove 'who_variant'; rename 'multiaa_comb_mutation' + final_df = final_df.drop(labels=['variant'], axis=1) + # add variant_pop_size + final_df['variant_pop_size'] = variant_pop_size + + # combine viral_lineages and clade_defining into key-value pairs + + # split viral_lineages and clade_defining by ',' + split_lineages = final_df['viral_lineages'].str.split( + pat=',').apply(pd.Series) # split at ,, form dataframe + split_clade_defining = final_df['clade_defining'].str.split( + pat=',').apply(pd.Series) # split at ,, form dataframe + # go through and make key-value pairs of corresponding columns + # from each + final_df['clade_defining_status'] = '' + for col in split_clade_defining.columns: + final_df['clade_defining_status'] = final_df[ + 'clade_defining_status'] + \ + split_lineages[col].astype( + str) + '=' + \ + split_clade_defining[ + col].astype(str) + '; ' + # drop clade_defining status for n/a strains and empty nan=nan pairs + final_df.clade_defining_status = \ + final_df.clade_defining_status.str.replace('n/a=n/a; ', + 'n/a; ') + final_df.clade_defining_status = \ + final_df.clade_defining_status.str.replace('nan=nan; ', '') + # strip trailing spaces and semicolons + final_df.clade_defining_status = \ + final_df.clade_defining_status.str.rstrip("; ") + + # drop repeated key-value pairs in each row (find these rows as + # they contain spaces) + for row in final_df['clade_defining_status']: + if ' ' in row: + mylist = row.split('; ') + newlist = [] + for pair in mylist: + pair = pair.replace(';', '') + pair = pair.lstrip(' ') + newlist.append(pair) + mylist = list(set(newlist)) + row_str = ', '.join(str(e) for e in mylist) + mask = final_df['clade_defining_status'] == row + final_df.loc[mask, 'clade_defining_status'] = row_str + + # drop repeated lineage names in each row of viral_lineages + # return an ordered list of lineages + for row in final_df['viral_lineages']: + if ' ' in row: + lineage_list = row.split(', ') + mylist = list(set(lineage_list)) + ''' + #order lineages alphanumerically + #split each element of mylist into a sublist, split at + the first '.' + split_list = + ''' + row_str = ', '.join(str(e) for e in mylist) + mask = final_df['viral_lineages'] == row + final_df.loc[mask, 'viral_lineages'] = row_str + + # reorder columns + cols = ['name', 'nt_name', 'aa_name', 'multi_aa_name', + 'multiaa_mutation_split_names', 'start', 'vcf_gene', + 'chrom_region', 'mutation_type', 'dp', 'obs_sample_size', + 'variant_pop_size', 'ps_filter', 'ps_exc', 'mat_pep_id', + 'mat_pep_desc', 'mat_pep_acc', 'ro', 'ao_by_var_seq', 'ao', + 'variant_seq', 'reference_seq', 'function_category', + 'citation', + 'citation_url', 'comb_mutation', 'function_description', + 'heterozygosity', 'viral_lineages', + 'clade_defining_status', 'status', + 'voi_designation_date', 'voc_designation_date', + 'vum_designation_date'] + final_df = final_df[cols] + + return final_df + + +if __name__ == '__main__': + + args = parse_args() + outfile = args.outtsv + gvf_list = args.gvf_files + + + + if not args.user: + clade_file = args.clades + # read in WHO variant/PANGO lineage .tsv + clades = pd.read_csv(clade_file, sep='\t', header=0, usecols=[ + 'variant', 'pango_lineage']) + + # get lowercase WHO variant names + who_variants_list = [] + if args.specify_variants: + who_variants_list = args.specify_variants + elif args.all_variants: + # if all variants, read the file and add from who_variant + # column, in case of Variant under monitoring, lineage will + # be added as the variant name to avoid several lineages + # being combined as one variant + for i in range(0, len(clades['variant'])): + if clades.loc[i, 'variant'] == "Unnamed": + who_variants_list.append(clades.loc[i, + 'pango_lineage']) + + else: + who_variants_list.append(clades.loc[i, + 'variant']) + + # for each variant, create a surveillance report + for who_variant in who_variants_list: + if "_" in who_variant: + who_variant = who_variant[0:who_variant.find( + "_")].capitalize() + who_variant[who_variant.find( + "_"):] + else: + who_variant = who_variant.capitalize() + + # get list of relevant pango lineages + pango_lineages = [] + for var in clades[clades['variant']==who_variant]['pango_lineage'].tolist(): + if "," in var: + for temp in var.split(","): + if "[" not in var: + pango_lineages.append(temp) + else: + parent = temp[0] + child = temp[2:-3].split("|") + for c in child: + pango_lineages.append(parent + str(c)) + pango_lineages.append(parent + str(c) + ".*") + else: + pango_lineages.append(var) + + #print(pango_lineages) + + # get list of gvf files pertaining to variant + gvf_files = [] + gvf_files = match_gvfs_to_who_variant( + pango_lineage_list=pango_lineages, + gvf_files_list=gvf_list) + print(str(len(gvf_files)) + " GVF files found for " + + who_variant + " variant.") + + + if len(gvf_files) > 0: + # convert all gvf files to tsv and concatenate them + print("") + print("Processing:") + print(gvf_files[0]) + gvf_df = gvf2tsv(gvf=gvf_files[0]) + if len(gvf_files) > 1: + for gvf in gvf_files[1:]: + print(gvf) + new_gvf_df = gvf2tsv(gvf=gvf) + gvf_df = pd.concat([gvf_df, new_gvf_df], + ignore_index=True) + + + if args.table: + # get variant population size + variant_pop_size = find_variant_pop_size(table=args.table, + pango_lineage_list= + pango_lineages) + + out_df = streamline_tsv(tsv_df=gvf_df) + filename = who_variant + '_' + outfile + out_df.to_csv(filename, sep='\t', index=False) + print("Processing complete.") + print(who_variant + " surveillance report saved as: " + + filename) + print("") + + + # if user-provided, who_variant is the provided filename + else: + gvf_files = gvf_list + if "_qc" not in gvf_list[0]: + who_variant = gvf_list[0].replace( + ".filtered.SNPEFF.annotated.gvf", "") + else: + who_variant = gvf_list[0].replace( + "_qc.sorted.variants.normalized.filtered.SNPEFF" + ".annotated.gvf", "") + + if args.table: + # get variant population size + variant_pop_size = find_variant_pop_size(table=args.table, + pango_lineage_list= + pango_lineages) + else: + variant_pop_size = "n/a" + + # if any GVF files are found, create a surveillance report + + + # convert all gvf files to tsv and concatenate them + print("Processing:") + print(gvf_files[0]) + gvf_df = gvf2tsv(gvf=gvf_files[0]) + + # streamline final concatenated df, reorder/rename + # columns where needed + out_df = streamline_user(tsv_df=gvf_df) + + # save report as a .tsv + filename = who_variant + '_' + outfile + out_df.to_csv(filename, sep='\t', index=False) + print("Processing complete.") + print(who_variant + " surveillance report saved as: " + + filename) + print("") From 58df48ad79fcec557f300eecf987a20f11a9ef60 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 03:26:47 -0700 Subject: [PATCH 059/161] Produce 1 TSV from GVF, ignoring clades --- bin/gvf2tsv.py | 432 ++----------------------------------------------- 1 file changed, 12 insertions(+), 420 deletions(-) diff --git a/bin/gvf2tsv.py b/bin/gvf2tsv.py index bf4f846d..ef1f2f1b 100755 --- a/bin/gvf2tsv.py +++ b/bin/gvf2tsv.py @@ -11,147 +11,21 @@ """ import argparse import pandas as pd -import os -import re from functions import separate_attributes def parse_args(): parser = argparse.ArgumentParser( description='Converts GVF files to a TSV report') - parser.add_argument('--gvf_files', type=str, default=None, - nargs='*', help='Paths to GVF files to process') - parser.add_argument('--clades', type=str, default=None, - help='TSV file of WHO strain names and ' - 'VOC/VOI status') + parser.add_argument('--gvf_file', type=str, default=None, + help='Paths to GVF files to process') parser.add_argument('--outtsv', type=str, default="surveillance_report.tsv", help='Filepath for finished .tsv') - group = parser.add_mutually_exclusive_group() - group.add_argument('--specify_variants', type=str, default=None, - nargs='*', help='Name(s) of WHO variant(s) to ' - 'make report for. Not ' - 'case-sensitive. Space separated.') - group.add_argument('--all_variants', action="store_true", - help='Create reports for all variants, ' - 'using all available reference lineage ' - 'gvf files. Not case-sensitive.') - parser.add_argument('--table', type=str, default=None, - help='Multi-strain TSV file generated in ' - 'workflow that contains num_seqs column') - parser.add_argument('--user', action="store_true", - help='Use user-uploaded file') return parser.parse_args() -def match_gvfs_to_who_variant(pango_lineage_list, gvf_files_list): - matched_files = [] - if len(pango_lineage_list) > 1: - for lineage in pango_lineage_list: - if "*" in lineage: - lineage = lineage.replace("*", "") - matched_files.extend([i for i in gvf_files_list if - i.startswith(lineage)]) - - matched_files = sorted(set(matched_files)) - else: - for lineage in pango_lineage_list: - # matched_files.extend([i for i in gvf_files_list if - # i.startswith(lineage)]) - matched_files = ([i for i in gvf_files_list if - i[:i.find("_")]==lineage]) - - return matched_files - - -def find_variant_pop_size(table, pango_lineage_list): - strain_tsv_df = pd.read_csv(table, header=0, - delim_whitespace=True, thousands=r',', - usecols=['file', 'num_seqs']) - - files = match_gvfs_to_who_variant( - pango_lineage_list=pango_lineage_list, - gvf_files_list=strain_tsv_df['file'].tolist()) - # print(files) - - pop_size = strain_tsv_df.loc[strain_tsv_df['file'].isin( - files), 'num_seqs'].sum() - return pop_size - - -def add_ao_by_variant_seq(ao_str, variant_seq_str): - """ - Takes a pair of strings like ao_str="7,7,24" and - variant_seq_str="T,T,T" or "8,21,3" and "T,T,A". - Output should be a string "T=38" (first case) or "T=29, A=3" ( - second case). - """ - ao_list = ao_str.split(',') - ao_list = [int(x) for x in ao_list] - var_str_list = variant_seq_str.split(',') - zipped_lists = list(zip(var_str_list, ao_list)) - - ao_dict = dict() - for pair in zipped_lists: - # if a variant seq isn't in the dictionary, add it - if pair[0] not in ao_dict: - ao_dict[pair[0]] = pair[1] - # if it's already there, add this ao to the existing key - else: - ao_dict[pair[0]] += pair[1] - - # create 3 strings: one for ao, one for var_seq, one for both - # joined together with an '=' between - joined_string = '' - ao_string = '' - var_string = '' - for item in list(ao_dict.items()): - joined_string = joined_string + item[0] + '=' + str(item[1]) \ - + ', ' - ao_string = ao_string + str(item[1]) + ',' - var_string = var_string + item[0] + ',' - joined_string = joined_string.rstrip(", ") - ao_string = ao_string.rstrip(", ") - var_string = var_string.rstrip(", ") - - return joined_string, ao_string, var_string - - -def add_one_from_each_lineage(count_str, lineage_str, mode): - """ - Takes a pair of strings like count_str="7,7,24" and - lineage_str="Q.3,Q.3,Q.1". - Output should be a string "31", adding unique lineage - values only, if mode='add'. - If mode='comma', returns a comma-separated set of values, - like "7,24". - """ - count_list = count_str.split(';') - if mode == 'add': - count_list = [int(x) for x in count_list] - lineage_str_list = lineage_str.replace(" ", "") - lineage_str_list = lineage_str.split(',') - zipped_lists = list(zip(lineage_str_list, count_list)) - - count_dict = dict() - for pair in zipped_lists: - # if a lineage isn't in the dictionary, add it - if pair[0] not in count_dict: - count_dict[pair[0]] = pair[1] - # if it's already there, do nothing - - # if mode=='comma', return a comma-separated string of values - if mode == 'comma': - return_str = ','.join(list(count_dict.values())) - # elif mode=='add', add up all the keys and return the value as a - # string - elif mode == 'add': - return_str = str(sum(list(count_dict.values()))) - - return return_str - - def gvf2tsv(gvf): # read in gvf gvf_columns = ['#seqid', '#source', '#type', '#start', '#end', @@ -182,306 +56,24 @@ def gvf2tsv(gvf): # plural df = df.rename(columns={'sample_size': 'obs_sample_size', 'viral_lineage': 'viral_lineages', - 'source': 'citation_url'}) + 'URL': 'citation_url'}) return df -def streamline_user(tsv_df): - tsv_df = tsv_df.rename(columns={'multiaa_comb_mutation': - 'multiaa_mutation_split_names'}) - cols = ['name', 'nt_name', 'aa_name', 'multi_aa_name', - 'multiaa_mutation_split_names', 'start', 'vcf_gene', - 'chrom_region', 'mutation_type', 'dp', 'obs_sample_size', - 'ps_filter', 'ps_exc', 'mat_pep_id', - 'mat_pep_desc', 'mat_pep_acc', 'ro', 'ao', - 'variant_seq', 'reference_seq', 'function_category', - 'citation', 'citation_url', 'comb_mutation', - 'function_description', - 'heterozygosity'] - tsv_df = tsv_df[cols] - - return tsv_df - - -def streamline_tsv(tsv_df): - # find identical rows across strains, and keep only one row. - # change n/a to 0 in 'ao' for counting purposes - tsv_df['ao'] = tsv_df['ao'].str.replace("n/a", "0") - - ''' - # make ro, dp, and obs_sample_size numeric - for colname in ['ro', 'dp', 'obs_sample_size']: - tsv_df[colname] = pd.to_numeric(tsv_df[colname], - errors='coerce') - ''' - # make obs_sample_size numeric - tsv_df['obs_sample_size'] = pd.to_numeric(tsv_df['obs_sample_size'], - errors='coerce') - - agg_dict = dict((col, 'first') for col in - tsv_df.columns.values.tolist()) - - agg_dict['obs_sample_size'] = 'sum' - # join some columns with commas - agg_dict['viral_lineages'] = ', '.join - agg_dict['clade_defining'] = ','.join - agg_dict['ao'] = ';'.join - agg_dict['dp'] = ';'.join - agg_dict['ro'] = ';'.join - agg_dict['variant_seq'] = ','.join - - cols_to_check = ['name', 'nt_name', 'aa_name', 'multi_aa_name', - 'multiaa_comb_mutation', 'start', - 'function_category', 'citation', - 'comb_mutation', 'function_description', - 'heterozygosity'] - - final_df = tsv_df.groupby(cols_to_check).agg(agg_dict) - final_df = final_df.rename(columns={'ao': 'ao_all', - 'variant_seq': - 'variant_seq_all', - 'multiaa_comb_mutation': - 'multiaa_mutation_split_names'}) - - # add dp, ro per mutation - for colname in ['dp', 'ro']: - final_df[colname] = [add_one_from_each_lineage(x, y, mode='add') - for x, y in - zip(final_df[colname], - final_df['viral_lineages'])] - - # add ao, variant_seq per mutation - for colname in ['ao_all', 'variant_seq_all']: - final_df[colname] = [ - add_one_from_each_lineage(x, y, mode='comma') for x, y in - zip(final_df[colname], - final_df['viral_lineages'])] - - # add ao according to the heterogeneous mutations - final_df['ao_by_var_seq'] = [add_ao_by_variant_seq(x, y)[0] for x, y - in zip(final_df['ao_all'], - final_df['variant_seq_all'])] - final_df['ao'] = [add_ao_by_variant_seq(x, y)[1] for x, y in - zip(final_df['ao_all'], - final_df['variant_seq_all'])] - final_df['variant_seq'] = [add_ao_by_variant_seq(x, y)[2] for x, y - in zip(final_df['ao_all'], - final_df['variant_seq_all'])] - - # remove 'who_variant'; rename 'multiaa_comb_mutation' - final_df = final_df.drop(labels=['variant'], axis=1) - # add variant_pop_size - final_df['variant_pop_size'] = variant_pop_size - - # combine viral_lineages and clade_defining into key-value pairs - - # split viral_lineages and clade_defining by ',' - split_lineages = final_df['viral_lineages'].str.split( - pat=',').apply(pd.Series) # split at ,, form dataframe - split_clade_defining = final_df['clade_defining'].str.split( - pat=',').apply(pd.Series) # split at ,, form dataframe - # go through and make key-value pairs of corresponding columns - # from each - final_df['clade_defining_status'] = '' - for col in split_clade_defining.columns: - final_df['clade_defining_status'] = final_df[ - 'clade_defining_status'] + \ - split_lineages[col].astype( - str) + '=' + \ - split_clade_defining[ - col].astype(str) + '; ' - # drop clade_defining status for n/a strains and empty nan=nan pairs - final_df.clade_defining_status = \ - final_df.clade_defining_status.str.replace('n/a=n/a; ', - 'n/a; ') - final_df.clade_defining_status = \ - final_df.clade_defining_status.str.replace('nan=nan; ', '') - # strip trailing spaces and semicolons - final_df.clade_defining_status = \ - final_df.clade_defining_status.str.rstrip("; ") - - # drop repeated key-value pairs in each row (find these rows as - # they contain spaces) - for row in final_df['clade_defining_status']: - if ' ' in row: - mylist = row.split('; ') - newlist = [] - for pair in mylist: - pair = pair.replace(';', '') - pair = pair.lstrip(' ') - newlist.append(pair) - mylist = list(set(newlist)) - row_str = ', '.join(str(e) for e in mylist) - mask = final_df['clade_defining_status'] == row - final_df.loc[mask, 'clade_defining_status'] = row_str - - # drop repeated lineage names in each row of viral_lineages - # return an ordered list of lineages - for row in final_df['viral_lineages']: - if ' ' in row: - lineage_list = row.split(', ') - mylist = list(set(lineage_list)) - ''' - #order lineages alphanumerically - #split each element of mylist into a sublist, split at - the first '.' - split_list = - ''' - row_str = ', '.join(str(e) for e in mylist) - mask = final_df['viral_lineages'] == row - final_df.loc[mask, 'viral_lineages'] = row_str - - # reorder columns - cols = ['name', 'nt_name', 'aa_name', 'multi_aa_name', - 'multiaa_mutation_split_names', 'start', 'vcf_gene', - 'chrom_region', 'mutation_type', 'dp', 'obs_sample_size', - 'variant_pop_size', 'ps_filter', 'ps_exc', 'mat_pep_id', - 'mat_pep_desc', 'mat_pep_acc', 'ro', 'ao_by_var_seq', 'ao', - 'variant_seq', 'reference_seq', 'function_category', - 'citation', - 'citation_url', 'comb_mutation', 'function_description', - 'heterozygosity', 'viral_lineages', - 'clade_defining_status', 'status', - 'voi_designation_date', 'voc_designation_date', - 'vum_designation_date'] - final_df = final_df[cols] - - return final_df - - if __name__ == '__main__': args = parse_args() outfile = args.outtsv - gvf_list = args.gvf_files - - - - if not args.user: - clade_file = args.clades - # read in WHO variant/PANGO lineage .tsv - clades = pd.read_csv(clade_file, sep='\t', header=0, usecols=[ - 'variant', 'pango_lineage']) - - # get lowercase WHO variant names - who_variants_list = [] - if args.specify_variants: - who_variants_list = args.specify_variants - elif args.all_variants: - # if all variants, read the file and add from who_variant - # column, in case of Variant under monitoring, lineage will - # be added as the variant name to avoid several lineages - # being combined as one variant - for i in range(0, len(clades['variant'])): - if clades.loc[i, 'variant'] == "Unnamed": - who_variants_list.append(clades.loc[i, - 'pango_lineage']) - - else: - who_variants_list.append(clades.loc[i, - 'variant']) - - # for each variant, create a surveillance report - for who_variant in who_variants_list: - if "_" in who_variant: - who_variant = who_variant[0:who_variant.find( - "_")].capitalize() + who_variant[who_variant.find( - "_"):] - else: - who_variant = who_variant.capitalize() - - # get list of relevant pango lineages - pango_lineages = [] - for var in clades[clades['variant']==who_variant]['pango_lineage'].tolist(): - if "," in var: - for temp in var.split(","): - if "[" not in var: - pango_lineages.append(temp) - else: - parent = temp[0] - child = temp[2:-3].split("|") - for c in child: - pango_lineages.append(parent + str(c)) - pango_lineages.append(parent + str(c) + ".*") - else: - pango_lineages.append(var) - - #print(pango_lineages) - - # get list of gvf files pertaining to variant - gvf_files = [] - gvf_files = match_gvfs_to_who_variant( - pango_lineage_list=pango_lineages, - gvf_files_list=gvf_list) - print(str(len(gvf_files)) + " GVF files found for " + - who_variant + " variant.") - - - if len(gvf_files) > 0: - # convert all gvf files to tsv and concatenate them - print("") - print("Processing:") - print(gvf_files[0]) - gvf_df = gvf2tsv(gvf=gvf_files[0]) - if len(gvf_files) > 1: - for gvf in gvf_files[1:]: - print(gvf) - new_gvf_df = gvf2tsv(gvf=gvf) - gvf_df = pd.concat([gvf_df, new_gvf_df], - ignore_index=True) - - - if args.table: - # get variant population size - variant_pop_size = find_variant_pop_size(table=args.table, - pango_lineage_list= - pango_lineages) - - out_df = streamline_tsv(tsv_df=gvf_df) - filename = who_variant + '_' + outfile - out_df.to_csv(filename, sep='\t', index=False) - print("Processing complete.") - print(who_variant + " surveillance report saved as: " + - filename) - print("") - - - # if user-provided, who_variant is the provided filename - else: - gvf_files = gvf_list - if "_qc" not in gvf_list[0]: - who_variant = gvf_list[0].replace( - ".filtered.SNPEFF.annotated.gvf", "") - else: - who_variant = gvf_list[0].replace( - "_qc.sorted.variants.normalized.filtered.SNPEFF" - ".annotated.gvf", "") - - if args.table: - # get variant population size - variant_pop_size = find_variant_pop_size(table=args.table, - pango_lineage_list= - pango_lineages) - else: - variant_pop_size = "n/a" - - # if any GVF files are found, create a surveillance report - + gvf_file = args.gvf_file - # convert all gvf files to tsv and concatenate them - print("Processing:") - print(gvf_files[0]) - gvf_df = gvf2tsv(gvf=gvf_files[0]) + # convert gvf file to tsv + print("") + print("Processing:") + print(gvf_file) - # streamline final concatenated df, reorder/rename - # columns where needed - out_df = streamline_user(tsv_df=gvf_df) + gvf_df = gvf2tsv(gvf=gvf_file) + gvf_df.to_csv(outfile, sep='\t', index=False) - # save report as a .tsv - filename = who_variant + '_' + outfile - out_df.to_csv(filename, sep='\t', index=False) - print("Processing complete.") - print(who_variant + " surveillance report saved as: " + - filename) - print("") + print("Processing complete.") + print("Surveillance report saved as: " + outfile) From 85a61608ba585efecd6693a3395620d0b274f49c Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 03:32:30 -0700 Subject: [PATCH 060/161] Update to match new GVF keys --- bin/gvf2indexandlog.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/bin/gvf2indexandlog.py b/bin/gvf2indexandlog.py index 9b33d7d7..d96146d9 100755 --- a/bin/gvf2indexandlog.py +++ b/bin/gvf2indexandlog.py @@ -53,7 +53,7 @@ def parse_args(): index = pd.DataFrame(np.empty((gvf.shape[0], len(index_cols))), columns=index_cols) # populate index df with gvf info index['pos'] = gvf['#start'] - index['mutation'] = gvf['Name'].str.replace("p.", "", regex=False) + index['mutation'] = gvf['original_mutation_description'].str.replace("p.", "", regex=False) index['hgvs_aa_mutation'] = gvf['hgvs_aa'] index['hgvs_nt_mutation'] = gvf['hgvs_nt'] index['alias'] = gvf['alias'] From ac59ae3a86c6d286e2f1778a3d7114c552ac04a0 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 03:43:57 -0700 Subject: [PATCH 061/161] add gene_orientation and strand_orientation to gvf --- bin/functions.py | 9 +++++++-- bin/vcf2gvf.py | 2 ++ 2 files changed, 9 insertions(+), 2 deletions(-) diff --git a/bin/functions.py b/bin/functions.py index c7d18063..a22e6e07 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -3,8 +3,9 @@ import logging # standard variables used by all scripts -empty_attributes = 'ID=;original_mutation_description=;alias=;gene=;gene_name=;gene_symbol=;product=; \ - protein_alias=;protein_name=;protein_symbol=;\ +empty_attributes = 'ID=;original_mutation_description=;alias=;gene=;gene_name=;gene_symbol=; \ + strand_orientation=;gene_orientation=; \ + product=;protein_alias=;protein_name=;protein_symbol=;\ protein_id=;alias_protein_id=;locus_tag=;ps_filter=;ps_exc=; \ mat_pep=;mat_pep_desc=;mat_pep_acc=;ro=;ao=;dp=;sample_size=; \ Reference_seq=;Variant_seq=;nt_name=;aa_name=;hgvs_nt=;hgvs_aa=;hgvs_alias=; \ @@ -542,11 +543,15 @@ def map_pos_to_gene_protein(pos, GENE_PROTEIN_POSITIONS_DICT): end = GENE_PROTEIN_POSITIONS_DICT[entry]["end"] gene_name = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_name"]["label"] gene_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_symbol"]["label"] + strand_orientation = GENE_PROTEIN_POSITIONS_DICT[entry]["strand_orientation"]["label"] + gene_orientation = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_orientation"]["label"] # fill in attributes for mutations in this gene region gene_mask = df[pos_column].astype(int).between(start, end, inclusive="both") df.loc[gene_mask, "gene_name"] = gene_name df.loc[gene_mask, "gene_symbol"] = gene_symbol + df.loc[gene_mask, "strand_orientation"] = strand_orientation + df.loc[gene_mask, "gene_orientation"] = gene_orientation # label all mutations that didn't belong to any gene as "intergenic" df.loc[df["gene"].isna(), "gene"] = "intergenic" diff --git a/bin/vcf2gvf.py b/bin/vcf2gvf.py index 649f3a76..047a69a6 100755 --- a/bin/vcf2gvf.py +++ b/bin/vcf2gvf.py @@ -86,6 +86,8 @@ def vcftogvf(vcf, strain, GENE_PROTEIN_POSITIONS_DICT, sample_size): new_gvf["gene"] = json_df["gene"] new_gvf["gene_name"] = json_df["gene_name"] new_gvf["gene_symbol"] = json_df["gene_symbol"] + new_gvf["strand_orientation"] = json_df["strand_orientation"] + new_gvf["gene_orientation"] = json_df["gene_orientation"] new_gvf["product"] = json_df["product"] new_gvf["protein_alias"] = json_df["protein_alias"] new_gvf["protein_name"] = json_df["protein_name"] From 49bbdba5d5e09946d3ea64431869dac8f93c81c1 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 13:16:00 -0700 Subject: [PATCH 062/161] change VP37 to be alias of OPG057 protein, and add to JSON --- assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json | 5 ++++- .../virus_genomeAnnotation/NC_063383.1/NC_063383.1_key.json | 2 +- 2 files changed, 5 insertions(+), 2 deletions(-) diff --git a/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json b/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json index 4bba8b06..c494742e 100644 --- a/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json +++ b/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json @@ -2050,7 +2050,10 @@ "protein_symbol": { "label": "Opg057 protein (MPOX)", "uri": "GENEPIO:0101754" - } + }, + "protein_alias": [ + "VP37" + ] }, "gene-NBT03_gp038": { "type": "gene", diff --git a/assets/virus_genomeAnnotation/NC_063383.1/NC_063383.1_key.json b/assets/virus_genomeAnnotation/NC_063383.1/NC_063383.1_key.json index d0449f5e..72f71dba 100644 --- a/assets/virus_genomeAnnotation/NC_063383.1/NC_063383.1_key.json +++ b/assets/virus_genomeAnnotation/NC_063383.1/NC_063383.1_key.json @@ -1,3 +1,3 @@ { - "MPXVgp025" : "VP37" + "MPXVgp045" : ["VP37"] } From 55186f23fc712c669f926650b5f4d233e580a863 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 13:21:56 -0700 Subject: [PATCH 063/161] remove VP37 mentions from MPXVgp025 --- assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json | 3 +-- 1 file changed, 1 insertion(+), 2 deletions(-) diff --git a/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json b/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json index c494742e..25e344ca 100644 --- a/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json +++ b/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json @@ -980,7 +980,7 @@ "uri": "GENEPIO:0700004" } }, - "VP37": { + "MPXVgp025": { "type": "CDS", "start": 21105, "end": 22433, @@ -997,7 +997,6 @@ "aa_start": 1, "aa_end": 442, "color": "rgb(196, 185, 69)", - "protein_alias": "VP37", "protein_name": { "label": "Ankyrin-like protein (1) (MPOX)", "uri": "GENEPIO:0101571" From 977fc0f4e903c263e20d654d42dac28114d70e6a Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 13:58:22 -0700 Subject: [PATCH 064/161] add protein_alias key to all CDS entries --- .../NC_063383.1/NC_063383.1.json | 535 ++++++++++++------ 1 file changed, 355 insertions(+), 180 deletions(-) diff --git a/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json b/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json index 25e344ca..4b720805 100644 --- a/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json +++ b/assets/virus_geneCoordinates/NC_063383.1/NC_063383.1.json @@ -69,7 +69,8 @@ "protein_symbol": { "label": "Opg001 protein (MPOX)", "uri": "GENEPIO:0101720" - } + }, + "protein_alias": [] }, "gene-NBT03_gp002": { "type": "gene", @@ -124,7 +125,8 @@ "protein_symbol": { "label": "Opg002 protein (MPOX)", "uri": "GENEPIO:0101721" - } + }, + "protein_alias": [] }, "gene-NBT03_gp003": { "type": "gene", @@ -179,7 +181,8 @@ "protein_symbol": { "label": "Opg003 protein (MPOX)", "uri": "GENEPIO:0101722" - } + }, + "protein_alias": [] }, "gene-NBT03_gp004": { "type": "gene", @@ -234,7 +237,8 @@ "protein_symbol": { "label": "Opg015 protein (MPOX)", "uri": "GENEPIO:0101723" - } + }, + "protein_alias": [] }, "gene-NBT03_gp005": { "type": "gene", @@ -289,7 +293,8 @@ "protein_symbol": { "label": "Opg019 protein (MPOX)", "uri": "GENEPIO:0101724" - } + }, + "protein_alias": [] }, "gene-NBT03_gp006": { "type": "gene", @@ -344,7 +349,8 @@ "protein_symbol": { "label": "Opg021 protein (MPOX)", "uri": "GENEPIO:0101725" - } + }, + "protein_alias": [] }, "gene-NBT03_gp007": { "type": "gene", @@ -399,7 +405,8 @@ "protein_symbol": { "label": "Opg022 protein (MPOX)", "uri": "GENEPIO:0101726" - } + }, + "protein_alias": [] }, "gene-NBT03_gp008": { "type": "gene", @@ -454,7 +461,8 @@ "protein_symbol": { "label": "Opg023 protein (MPOX)", "uri": "GENEPIO:0101727" - } + }, + "protein_alias": [] }, "gene-NBT03_gp009": { "type": "gene", @@ -509,7 +517,8 @@ "protein_symbol": { "label": "Opg024 protein (MPOX)", "uri": "GENEPIO:0101728" - } + }, + "protein_alias": [] }, "gene-NBT03_gp010": { "type": "gene", @@ -564,7 +573,8 @@ "protein_symbol": { "label": "Opg025 protein (MPOX)", "uri": "GENEPIO:0101729" - } + }, + "protein_alias": [] }, "gene-NBT03_gp011": { "type": "gene", @@ -619,7 +629,8 @@ "protein_symbol": { "label": "Opg027 protein (MPOX)", "uri": "GENEPIO:0101730" - } + }, + "protein_alias": [] }, "gene-NBT03_gp012": { "type": "gene", @@ -674,7 +685,8 @@ "protein_symbol": { "label": "Opg029 protein (MPOX)", "uri": "GENEPIO:0101731" - } + }, + "protein_alias": [] }, "gene-NBT03_gp013": { "type": "gene", @@ -729,7 +741,8 @@ "protein_symbol": { "label": "Opg030 protein (MPOX)", "uri": "GENEPIO:0101732" - } + }, + "protein_alias": [] }, "gene-NBT03_gp014": { "type": "gene", @@ -784,7 +797,8 @@ "protein_symbol": { "label": "Opg031 protein (MPOX)", "uri": "GENEPIO:0101733" - } + }, + "protein_alias": [] }, "gene-NBT03_gp015": { "type": "gene", @@ -839,7 +853,8 @@ "protein_symbol": { "label": "Opg034 protein (MPOX)", "uri": "GENEPIO:0101734" - } + }, + "protein_alias": [] }, "gene-NBT03_gp016": { "type": "gene", @@ -894,7 +909,8 @@ "protein_symbol": { "label": "Opg035 protein (MPOX)", "uri": "GENEPIO:0101735" - } + }, + "protein_alias": [] }, "gene-NBT03_gp017": { "type": "gene", @@ -949,7 +965,8 @@ "protein_symbol": { "label": "Opg035 protein (MPOX)", "uri": "GENEPIO:0101735" - } + }, + "protein_alias": [] }, "gene-NBT03_gp018": { "type": "gene", @@ -1004,7 +1021,8 @@ "protein_symbol": { "label": "Opg037 protein (MPOX)", "uri": "GENEPIO:0101736" - } + }, + "protein_alias": [] }, "gene-NBT03_gp019": { "type": "gene", @@ -1059,7 +1077,8 @@ "protein_symbol": { "label": "Opg038 protein (MPOX)", "uri": "GENEPIO:0101737" - } + }, + "protein_alias": [] }, "gene-NBT03_gp020": { "type": "gene", @@ -1114,7 +1133,8 @@ "protein_symbol": { "label": "Opg039 protein (MPOX)", "uri": "GENEPIO:0101738" - } + }, + "protein_alias": [] }, "gene-NBT03_gp021": { "type": "gene", @@ -1169,7 +1189,8 @@ "protein_symbol": { "label": "Opg040 protein (MPOX)", "uri": "GENEPIO:0101739" - } + }, + "protein_alias": [] }, "gene-NBT03_gp022": { "type": "gene", @@ -1224,7 +1245,8 @@ "protein_symbol": { "label": "Opg042 protein (MPOX)", "uri": "GENEPIO:0101740" - } + }, + "protein_alias": [] }, "gene-NBT03_gp023": { "type": "gene", @@ -1279,7 +1301,8 @@ "protein_symbol": { "label": "Opg043 protein (MPOX)", "uri": "GENEPIO:0101741" - } + }, + "protein_alias": [] }, "gene-NBT03_gp024": { "type": "gene", @@ -1334,7 +1357,8 @@ "protein_symbol": { "label": "Opg043 protein (MPOX)", "uri": "GENEPIO:0101741" - } + }, + "protein_alias": [] }, "gene-NBT03_gp025": { "type": "gene", @@ -1389,7 +1413,8 @@ "protein_symbol": { "label": "Opg045 protein (MPOX)", "uri": "GENEPIO:0101742" - } + }, + "protein_alias": [] }, "gene-NBT03_gp026": { "type": "gene", @@ -1444,7 +1469,8 @@ "protein_symbol": { "label": "Opg046 protein (MPOX)", "uri": "GENEPIO:0101743" - } + }, + "protein_alias": [] }, "gene-NBT03_gp027": { "type": "gene", @@ -1499,7 +1525,8 @@ "protein_symbol": { "label": "Opg047 protein (MPOX)", "uri": "GENEPIO:0101744" - } + }, + "protein_alias": [] }, "gene-NBT03_gp028": { "type": "gene", @@ -1554,7 +1581,8 @@ "protein_symbol": { "label": "Opg048 protein (MPOX)", "uri": "GENEPIO:0101745" - } + }, + "protein_alias": [] }, "gene-NBT03_gp029": { "type": "gene", @@ -1609,7 +1637,8 @@ "protein_symbol": { "label": "Opg049 protein (MPOX)", "uri": "GENEPIO:0101746" - } + }, + "protein_alias": [] }, "gene-NBT03_gp030": { "type": "gene", @@ -1664,7 +1693,8 @@ "protein_symbol": { "label": "Opg050 protein (MPOX)", "uri": "GENEPIO:0101747" - } + }, + "protein_alias": [] }, "gene-NBT03_gp031": { "type": "gene", @@ -1719,7 +1749,8 @@ "protein_symbol": { "label": "Opg051 protein (MPOX)", "uri": "GENEPIO:0101748" - } + }, + "protein_alias": [] }, "gene-NBT03_gp032": { "type": "gene", @@ -1774,7 +1805,8 @@ "protein_symbol": { "label": "Opg052 protein (MPOX)", "uri": "GENEPIO:0101749" - } + }, + "protein_alias": [] }, "gene-NBT03_gp033": { "type": "gene", @@ -1829,7 +1861,8 @@ "protein_symbol": { "label": "Opg053 protein (MPOX)", "uri": "GENEPIO:0101750" - } + }, + "protein_alias": [] }, "gene-NBT03_gp034": { "type": "gene", @@ -1884,7 +1917,8 @@ "protein_symbol": { "label": "Opg054 protein (MPOX)", "uri": "GENEPIO:0101751" - } + }, + "protein_alias": [] }, "gene-NBT03_gp035": { "type": "gene", @@ -1939,7 +1973,8 @@ "protein_symbol": { "label": "Opg055 protein (MPOX)", "uri": "GENEPIO:0101752" - } + }, + "protein_alias": [] }, "gene-NBT03_gp036": { "type": "gene", @@ -1994,7 +2029,8 @@ "protein_symbol": { "label": "Opg056 protein (MPOX)", "uri": "GENEPIO:0101753" - } + }, + "protein_alias": [] }, "gene-NBT03_gp037": { "type": "gene", @@ -2050,9 +2086,7 @@ "label": "Opg057 protein (MPOX)", "uri": "GENEPIO:0101754" }, - "protein_alias": [ - "VP37" - ] + "protein_alias": ["VP37"] }, "gene-NBT03_gp038": { "type": "gene", @@ -2107,7 +2141,8 @@ "protein_symbol": { "label": "Opg058 protein (MPOX)", "uri": "GENEPIO:0101755" - } + }, + "protein_alias": [] }, "gene-NBT03_gp039": { "type": "gene", @@ -2161,7 +2196,8 @@ "protein_symbol": { "label": "Opg059 protein (MPOX)", "uri": "GENEPIO:0101756" - } + }, + "protein_alias": [] }, "gene-NBT03_gp040": { "type": "gene", @@ -2216,7 +2252,8 @@ "protein_symbol": { "label": "Opg060 protein (MPOX)", "uri": "GENEPIO:0101757" - } + }, + "protein_alias": [] }, "gene-NBT03_gp041": { "type": "gene", @@ -2271,7 +2308,8 @@ "protein_symbol": { "label": "Opg061 protein (MPOX)", "uri": "GENEPIO:0101758" - } + }, + "protein_alias": [] }, "gene-NBT03_gp042": { "type": "gene", @@ -2326,7 +2364,8 @@ "protein_symbol": { "label": "Opg062 protein (MPOX)", "uri": "GENEPIO:0101759" - } + }, + "protein_alias": [] }, "gene-NBT03_gp043": { "type": "gene", @@ -2381,7 +2420,8 @@ "protein_symbol": { "label": "Opg063 protein (MPOX)", "uri": "GENEPIO:0101760" - } + }, + "protein_alias": [] }, "gene-NBT03_gp044": { "type": "gene", @@ -2436,7 +2476,8 @@ "protein_symbol": { "label": "Opg064 protein (MPOX)", "uri": "GENEPIO:0101761" - } + }, + "protein_alias": [] }, "gene-NBT03_gp045": { "type": "gene", @@ -2491,7 +2532,8 @@ "protein_symbol": { "label": "Opg065 protein (MPOX)", "uri": "GENEPIO:0101762" - } + }, + "protein_alias": [] }, "gene-NBT03_gp046": { "type": "gene", @@ -2546,7 +2588,8 @@ "protein_symbol": { "label": "Opg066 protein (MPOX)", "uri": "GENEPIO:0101763" - } + }, + "protein_alias": [] }, "gene-NBT03_gp047": { "type": "gene", @@ -2601,7 +2644,8 @@ "protein_symbol": { "label": "Opg068 protein (MPOX)", "uri": "GENEPIO:0101764" - } + }, + "protein_alias": [] }, "gene-NBT03_gp048": { "type": "gene", @@ -2656,7 +2700,8 @@ "protein_symbol": { "label": "Opg069 protein (MPOX)", "uri": "GENEPIO:0101765" - } + }, + "protein_alias": [] }, "gene-NBT03_gp049": { "type": "gene", @@ -2711,7 +2756,8 @@ "protein_symbol": { "label": "Opg070 protein (MPOX)", "uri": "GENEPIO:0101766" - } + }, + "protein_alias": [] }, "gene-NBT03_gp050": { "type": "gene", @@ -2766,7 +2812,8 @@ "protein_symbol": { "label": "Opg071 protein (MPOX)", "uri": "GENEPIO:0101767" - } + }, + "protein_alias": [] }, "gene-NBT03_gp051": { "type": "gene", @@ -2821,7 +2868,8 @@ "protein_symbol": { "label": "Opg072 protein (MPOX)", "uri": "GENEPIO:0101768" - } + }, + "protein_alias": [] }, "gene-NBT03_gp052": { "type": "gene", @@ -2874,7 +2922,8 @@ "protein_symbol": { "label": "Opg073 protein (MPOX)", "uri": "GENEPIO:0101769" - } + }, + "protein_alias": [] }, "gene-NBT03_gp053": { "type": "gene", @@ -2929,7 +2978,8 @@ "protein_symbol": { "label": "Opg074 protein (MPOX)", "uri": "GENEPIO:0101770" - } + }, + "protein_alias": [] }, "gene-NBT03_gp054": { "type": "gene", @@ -2984,7 +3034,8 @@ "protein_symbol": { "label": "Opg075 protein (MPOX)", "uri": "GENEPIO:0101771" - } + }, + "protein_alias": [] }, "gene-NBT03_gp055": { "type": "gene", @@ -3037,7 +3088,8 @@ "protein_symbol": { "label": "Opg075 protein (MPOX)", "uri": "GENEPIO:0101771" - } + }, + "protein_alias": [] }, "gene-NBT03_gp056": { "type": "gene", @@ -3092,7 +3144,8 @@ "protein_symbol": { "label": "Opg077 protein (MPOX)", "uri": "GENEPIO:0101772" - } + }, + "protein_alias": [] }, "gene-NBT03_gp057": { "type": "gene", @@ -3147,7 +3200,8 @@ "protein_symbol": { "label": "Opg078 protein (MPOX)", "uri": "GENEPIO:0101773" - } + }, + "protein_alias": [] }, "gene-NBT03_gp058": { "type": "gene", @@ -3202,7 +3256,8 @@ "protein_symbol": { "label": "Opg079 protein (MPOX)", "uri": "GENEPIO:0101774" - } + }, + "protein_alias": [] }, "gene-NBT03_gp059": { "type": "gene", @@ -3257,7 +3312,8 @@ "protein_symbol": { "label": "Opg080 protein (MPOX)", "uri": "GENEPIO:0101775" - } + }, + "protein_alias": [] }, "gene-NBT03_gp060": { "type": "gene", @@ -3312,7 +3368,8 @@ "protein_symbol": { "label": "Opg081 protein (MPOX)", "uri": "GENEPIO:0101776" - } + }, + "protein_alias": [] }, "gene-NBT03_gp061": { "type": "gene", @@ -3367,7 +3424,8 @@ "protein_symbol": { "label": "Opg082 protein (MPOX)", "uri": "GENEPIO:0101777" - } + }, + "protein_alias": [] }, "gene-NBT03_gp062": { "type": "gene", @@ -3422,7 +3480,8 @@ "protein_symbol": { "label": "Opg083 protein (MPOX)", "uri": "GENEPIO:0101778" - } + }, + "protein_alias": [] }, "gene-NBT03_gp063": { "type": "gene", @@ -3477,7 +3536,8 @@ "protein_symbol": { "label": "Opg084 protein (MPOX)", "uri": "GENEPIO:0101779" - } + }, + "protein_alias": [] }, "gene-NBT03_gp064": { "type": "gene", @@ -3532,7 +3592,8 @@ "protein_symbol": { "label": "Opg085 protein (MPOX)", "uri": "GENEPIO:0101780" - } + }, + "protein_alias": [] }, "gene-NBT03_gp065": { "type": "gene", @@ -3587,7 +3648,8 @@ "protein_symbol": { "label": "Opg086 protein (MPOX)", "uri": "GENEPIO:0101781" - } + }, + "protein_alias": [] }, "gene-NBT03_gp066": { "type": "gene", @@ -3642,7 +3704,8 @@ "protein_symbol": { "label": "Opg087 protein (MPOX)", "uri": "GENEPIO:0101782" - } + }, + "protein_alias": [] }, "gene-NBT03_gp067": { "type": "gene", @@ -3697,7 +3760,8 @@ "protein_symbol": { "label": "Opg088 protein (MPOX)", "uri": "GENEPIO:0101783" - } + }, + "protein_alias": [] }, "gene-NBT03_gp068": { "type": "gene", @@ -3752,7 +3816,8 @@ "protein_symbol": { "label": "Opg089 protein (MPOX)", "uri": "GENEPIO:0101784" - } + }, + "protein_alias": [] }, "gene-NBT03_gp069": { "type": "gene", @@ -3807,7 +3872,8 @@ "protein_symbol": { "label": "Opg090 protein (MPOX)", "uri": "GENEPIO:0101785" - } + }, + "protein_alias": [] }, "gene-NBT03_gp070": { "type": "gene", @@ -3862,7 +3928,8 @@ "protein_symbol": { "label": "Opg091 protein (MPOX)", "uri": "GENEPIO:0101786" - } + }, + "protein_alias": [] }, "gene-NBT03_gp071": { "type": "gene", @@ -3917,7 +3984,8 @@ "protein_symbol": { "label": "Opg092 protein (MPOX)", "uri": "GENEPIO:0101787" - } + }, + "protein_alias": [] }, "gene-NBT03_gp072": { "type": "gene", @@ -3972,7 +4040,8 @@ "protein_symbol": { "label": "Opg093 protein (MPOX)", "uri": "GENEPIO:0101788" - } + }, + "protein_alias": [] }, "gene-NBT03_gp073": { "type": "gene", @@ -4027,7 +4096,8 @@ "protein_symbol": { "label": "Opg094 protein (MPOX)", "uri": "GENEPIO:0101789" - } + }, + "protein_alias": [] }, "gene-NBT03_gp074": { "type": "gene", @@ -4082,7 +4152,8 @@ "protein_symbol": { "label": "Opg095 protein (MPOX)", "uri": "GENEPIO:0101790" - } + }, + "protein_alias": [] }, "gene-NBT03_gp075": { "type": "gene", @@ -4137,7 +4208,8 @@ "protein_symbol": { "label": "Opg096 protein (MPOX)", "uri": "GENEPIO:0101791" - } + }, + "protein_alias": [] }, "gene-NBT03_gp076": { "type": "gene", @@ -4192,7 +4264,8 @@ "protein_symbol": { "label": "Opg097 protein (MPOX)", "uri": "GENEPIO:0101792" - } + }, + "protein_alias": [] }, "gene-NBT03_gp077": { "type": "gene", @@ -4247,7 +4320,8 @@ "protein_symbol": { "label": "Opg098 protein (MPOX)", "uri": "GENEPIO:0101793" - } + }, + "protein_alias": [] }, "gene-NBT03_gp078": { "type": "gene", @@ -4302,7 +4376,8 @@ "protein_symbol": { "label": "Opg099 protein (MPOX)", "uri": "GENEPIO:0101794" - } + }, + "protein_alias": [] }, "gene-NBT03_gp079": { "type": "gene", @@ -4357,7 +4432,8 @@ "protein_symbol": { "label": "Opg100 protein (MPOX)", "uri": "GENEPIO:0101795" - } + }, + "protein_alias": [] }, "gene-NBT03_gp080": { "type": "gene", @@ -4412,7 +4488,8 @@ "protein_symbol": { "label": "Opg101 protein (MPOX)", "uri": "GENEPIO:0101796" - } + }, + "protein_alias": [] }, "gene-NBT03_gp081": { "type": "gene", @@ -4467,7 +4544,8 @@ "protein_symbol": { "label": "Opg102 protein (MPOX)", "uri": "GENEPIO:0101797" - } + }, + "protein_alias": [] }, "gene-NBT03_gp082": { "type": "gene", @@ -4522,7 +4600,8 @@ "protein_symbol": { "label": "Opg103 protein (MPOX)", "uri": "GENEPIO:0101798" - } + }, + "protein_alias": [] }, "gene-NBT03_gp083": { "type": "gene", @@ -4577,7 +4656,8 @@ "protein_symbol": { "label": "Opg104 protein (MPOX)", "uri": "GENEPIO:0101799" - } + }, + "protein_alias": [] }, "gene-NBT03_gp084": { "type": "gene", @@ -4632,7 +4712,8 @@ "protein_symbol": { "label": "Opg105 protein (MPOX)", "uri": "GENEPIO:0101800" - } + }, + "protein_alias": [] }, "gene-NBT03_gp085": { "type": "gene", @@ -4687,7 +4768,8 @@ "protein_symbol": { "label": "Opg106 protein (MPOX)", "uri": "GENEPIO:0101801" - } + }, + "protein_alias": [] }, "gene-NBT03_gp086": { "type": "gene", @@ -4742,7 +4824,8 @@ "protein_symbol": { "label": "Opg107 protein (MPOX)", "uri": "GENEPIO:0101802" - } + }, + "protein_alias": [] }, "gene-NBT03_gp087": { "type": "gene", @@ -4797,7 +4880,8 @@ "protein_symbol": { "label": "Opg108 protein (MPOX)", "uri": "GENEPIO:0101803" - } + }, + "protein_alias": [] }, "gene-NBT03_gp088": { "type": "gene", @@ -4852,7 +4936,8 @@ "protein_symbol": { "label": "Opg109 protein (MPOX)", "uri": "GENEPIO:0101804" - } + }, + "protein_alias": [] }, "gene-NBT03_gp089": { "type": "gene", @@ -4907,7 +4992,8 @@ "protein_symbol": { "label": "Opg110 protein (MPOX)", "uri": "GENEPIO:0101805" - } + }, + "protein_alias": [] }, "gene-NBT03_gp090": { "type": "gene", @@ -4962,7 +5048,8 @@ "protein_symbol": { "label": "Opg111 protein (MPOX)", "uri": "GENEPIO:0101806" - } + }, + "protein_alias": [] }, "gene-NBT03_gp091": { "type": "gene", @@ -5017,7 +5104,8 @@ "protein_symbol": { "label": "Opg112 protein (MPOX)", "uri": "GENEPIO:0101807" - } + }, + "protein_alias": [] }, "gene-NBT03_gp092": { "type": "gene", @@ -5072,7 +5160,8 @@ "protein_symbol": { "label": "Opg113 protein (MPOX)", "uri": "GENEPIO:0101808" - } + }, + "protein_alias": [] }, "gene-NBT03_gp093": { "type": "gene", @@ -5127,7 +5216,8 @@ "protein_symbol": { "label": "Opg114 protein (MPOX)", "uri": "GENEPIO:0101809" - } + }, + "protein_alias": [] }, "gene-NBT03_gp094": { "type": "gene", @@ -5182,7 +5272,8 @@ "protein_symbol": { "label": "Opg115 protein (MPOX)", "uri": "GENEPIO:0101810" - } + }, + "protein_alias": [] }, "gene-NBT03_gp095": { "type": "gene", @@ -5237,7 +5328,8 @@ "protein_symbol": { "label": "Opg116 protein (MPOX)", "uri": "GENEPIO:0101811" - } + }, + "protein_alias": [] }, "gene-NBT03_gp096": { "type": "gene", @@ -5292,7 +5384,8 @@ "protein_symbol": { "label": "Opg117 protein (MPOX)", "uri": "GENEPIO:0101812" - } + }, + "protein_alias": [] }, "gene-NBT03_gp097": { "type": "gene", @@ -5347,7 +5440,8 @@ "protein_symbol": { "label": "Opg118 protein (MPOX)", "uri": "GENEPIO:0101813" - } + }, + "protein_alias": [] }, "gene-NBT03_gp098": { "type": "gene", @@ -5402,7 +5496,8 @@ "protein_symbol": { "label": "Opg119 protein (MPOX)", "uri": "GENEPIO:0101814" - } + }, + "protein_alias": [] }, "gene-NBT03_gp099": { "type": "gene", @@ -5457,7 +5552,8 @@ "protein_symbol": { "label": "Opg120 protein (MPOX)", "uri": "GENEPIO:0101815" - } + }, + "protein_alias": [] }, "gene-NBT03_gp100": { "type": "gene", @@ -5512,7 +5608,8 @@ "protein_symbol": { "label": "Opg121 protein (MPOX)", "uri": "GENEPIO:0101816" - } + }, + "protein_alias": [] }, "gene-NBT03_gp101": { "type": "gene", @@ -5567,7 +5664,8 @@ "protein_symbol": { "label": "Opg122 protein (MPOX)", "uri": "GENEPIO:0101817" - } + }, + "protein_alias": [] }, "gene-NBT03_gp102": { "type": "gene", @@ -5622,7 +5720,8 @@ "protein_symbol": { "label": "Opg123 protein (MPOX)", "uri": "GENEPIO:0101818" - } + }, + "protein_alias": [] }, "gene-NBT03_gp103": { "type": "gene", @@ -5677,7 +5776,8 @@ "protein_symbol": { "label": "Opg124 protein (MPOX)", "uri": "GENEPIO:0101819" - } + }, + "protein_alias": [] }, "gene-NBT03_gp104": { "type": "gene", @@ -5732,7 +5832,8 @@ "protein_symbol": { "label": "Opg125 protein (MPOX)", "uri": "GENEPIO:0101820" - } + }, + "protein_alias": [] }, "gene-NBT03_gp105": { "type": "gene", @@ -5787,7 +5888,8 @@ "protein_symbol": { "label": "Opg126 protein (MPOX)", "uri": "GENEPIO:0101821" - } + }, + "protein_alias": [] }, "gene-NBT03_gp106": { "type": "gene", @@ -5842,7 +5944,8 @@ "protein_symbol": { "label": "Opg127 protein (MPOX)", "uri": "GENEPIO:0101822" - } + }, + "protein_alias": [] }, "gene-NBT03_gp107": { "type": "gene", @@ -5897,7 +6000,8 @@ "protein_symbol": { "label": "Opg128 protein (MPOX)", "uri": "GENEPIO:0101823" - } + }, + "protein_alias": [] }, "gene-NBT03_gp108": { "type": "gene", @@ -5952,7 +6056,8 @@ "protein_symbol": { "label": "Opg129 protein (MPOX)", "uri": "GENEPIO:0101824" - } + }, + "protein_alias": [] }, "gene-NBT03_gp109": { "type": "gene", @@ -6007,7 +6112,8 @@ "protein_symbol": { "label": "Opg130 protein (MPOX)", "uri": "GENEPIO:0101825" - } + }, + "protein_alias": [] }, "gene-NBT03_gp110": { "type": "gene", @@ -6062,7 +6168,8 @@ "protein_symbol": { "label": "Opg131 protein (MPOX)", "uri": "GENEPIO:0101826" - } + }, + "protein_alias": [] }, "gene-NBT03_gp111": { "type": "gene", @@ -6117,7 +6224,8 @@ "protein_symbol": { "label": "Opg132 protein (MPOX)", "uri": "GENEPIO:0101827" - } + }, + "protein_alias": [] }, "gene-NBT03_gp112": { "type": "gene", @@ -6172,7 +6280,8 @@ "protein_symbol": { "label": "Opg133 protein (MPOX)", "uri": "GENEPIO:0101828" - } + }, + "protein_alias": [] }, "gene-NBT03_gp113": { "type": "gene", @@ -6227,7 +6336,8 @@ "protein_symbol": { "label": "Opg134 protein (MPOX)", "uri": "GENEPIO:0101829" - } + }, + "protein_alias": [] }, "gene-NBT03_gp114": { "type": "gene", @@ -6282,7 +6392,8 @@ "protein_symbol": { "label": "Opg135 protein (MPOX)", "uri": "GENEPIO:0101830" - } + }, + "protein_alias": [] }, "gene-NBT03_gp115": { "type": "gene", @@ -6337,7 +6448,8 @@ "protein_symbol": { "label": "Opg136 protein (MPOX)", "uri": "GENEPIO:0101831" - } + }, + "protein_alias": [] }, "gene-NBT03_gp116": { "type": "gene", @@ -6392,7 +6504,8 @@ "protein_symbol": { "label": "Opg137 protein (MPOX)", "uri": "GENEPIO:0101832" - } + }, + "protein_alias": [] }, "gene-NBT03_gp117": { "type": "gene", @@ -6447,7 +6560,8 @@ "protein_symbol": { "label": "Opg138 protein (MPOX)", "uri": "GENEPIO:0101833" - } + }, + "protein_alias": [] }, "gene-NBT03_gp118": { "type": "gene", @@ -6502,7 +6616,8 @@ "protein_symbol": { "label": "Opg139 protein (MPOX)", "uri": "GENEPIO:0101834" - } + }, + "protein_alias": [] }, "gene-NBT03_gp119": { "type": "gene", @@ -6557,7 +6672,8 @@ "protein_symbol": { "label": "Opg140 protein (MPOX)", "uri": "GENEPIO:0101835" - } + }, + "protein_alias": [] }, "gene-NBT03_gp120": { "type": "gene", @@ -6611,7 +6727,8 @@ "protein_symbol": { "label": "Opg141 protein (MPOX)", "uri": "GENEPIO:0101836" - } + }, + "protein_alias": [] }, "gene-NBT03_gp121": { "type": "gene", @@ -6666,7 +6783,8 @@ "protein_symbol": { "label": "Opg142 protein (MPOX)", "uri": "GENEPIO:0101837" - } + }, + "protein_alias": [] }, "gene-NBT03_gp122": { "type": "gene", @@ -6721,7 +6839,8 @@ "protein_symbol": { "label": "Opg143 protein (MPOX)", "uri": "GENEPIO:0101838" - } + }, + "protein_alias": [] }, "gene-NBT03_gp123": { "type": "gene", @@ -6776,7 +6895,8 @@ "protein_symbol": { "label": "Opg144 protein (MPOX)", "uri": "GENEPIO:0101839" - } + }, + "protein_alias": [] }, "gene-NBT03_gp124": { "type": "gene", @@ -6831,7 +6951,8 @@ "protein_symbol": { "label": "Opg145 protein (MPOX)", "uri": "GENEPIO:0101840" - } + }, + "protein_alias": [] }, "gene-NBT03_gp125": { "type": "gene", @@ -6886,7 +7007,8 @@ "protein_symbol": { "label": "Opg146 protein (MPOX)", "uri": "GENEPIO:0101841" - } + }, + "protein_alias": [] }, "gene-NBT03_gp126": { "type": "gene", @@ -6941,7 +7063,8 @@ "protein_symbol": { "label": "Opg147 protein (MPOX)", "uri": "GENEPIO:0101842" - } + }, + "protein_alias": [] }, "gene-NBT03_gp127": { "type": "gene", @@ -6996,7 +7119,8 @@ "protein_symbol": { "label": "Opg148 protein (MPOX)", "uri": "GENEPIO:0101843" - } + }, + "protein_alias": [] }, "gene-NBT03_gp128": { "type": "gene", @@ -7051,7 +7175,8 @@ "protein_symbol": { "label": "Opg149 protein (MPOX)", "uri": "GENEPIO:0101844" - } + }, + "protein_alias": [] }, "gene-NBT03_gp129": { "type": "gene", @@ -7106,7 +7231,8 @@ "protein_symbol": { "label": "Opg150 protein (MPOX)", "uri": "GENEPIO:0101845" - } + }, + "protein_alias": [] }, "gene-NBT03_gp130": { "type": "gene", @@ -7161,7 +7287,8 @@ "protein_symbol": { "label": "Opg151 protein (MPOX)", "uri": "GENEPIO:0101846" - } + }, + "protein_alias": [] }, "gene-NBT03_gp131": { "type": "gene", @@ -7216,7 +7343,8 @@ "protein_symbol": { "label": "Opg153 protein (MPOX)", "uri": "GENEPIO:0101847" - } + }, + "protein_alias": [] }, "gene-NBT03_gp132": { "type": "gene", @@ -7271,7 +7399,8 @@ "protein_symbol": { "label": "Opg154 protein (MPOX)", "uri": "GENEPIO:0101848" - } + }, + "protein_alias": [] }, "gene-NBT03_gp133": { "type": "gene", @@ -7326,7 +7455,8 @@ "protein_symbol": { "label": "Opg155 protein (MPOX)", "uri": "GENEPIO:0101849" - } + }, + "protein_alias": [] }, "gene-NBT03_gp134": { "type": "gene", @@ -7381,7 +7511,8 @@ "protein_symbol": { "label": "Opg156 protein (MPOX)", "uri": "GENEPIO:0101850" - } + }, + "protein_alias": [] }, "gene-NBT03_gp135": { "type": "gene", @@ -7436,7 +7567,8 @@ "protein_symbol": { "label": "Opg157 protein (MPOX)", "uri": "GENEPIO:0101851" - } + }, + "protein_alias": [] }, "gene-NBT03_gp136": { "type": "gene", @@ -7490,7 +7622,8 @@ "protein_symbol": { "label": "Opg158 protein (MPOX)", "uri": "GENEPIO:0101852" - } + }, + "protein_alias": [] }, "gene-NBT03_gp137": { "type": "gene", @@ -7545,7 +7678,8 @@ "protein_symbol": { "label": "Opg159 protein (MPOX)", "uri": "GENEPIO:0101853" - } + }, + "protein_alias": [] }, "gene-NBT03_gp138": { "type": "gene", @@ -7600,7 +7734,8 @@ "protein_symbol": { "label": "Opg160 protein (MPOX)", "uri": "GENEPIO:0101854" - } + }, + "protein_alias": [] }, "gene-NBT03_gp139": { "type": "gene", @@ -7655,7 +7790,8 @@ "protein_symbol": { "label": "Opg161 protein (MPOX)", "uri": "GENEPIO:0101855" - } + }, + "protein_alias": [] }, "gene-NBT03_gp140": { "type": "gene", @@ -7710,7 +7846,8 @@ "protein_symbol": { "label": "Opg162 protein (MPOX)", "uri": "GENEPIO:0101856" - } + }, + "protein_alias": [] }, "gene-NBT03_gp141": { "type": "gene", @@ -7765,7 +7902,8 @@ "protein_symbol": { "label": "Opg163 protein (MPOX)", "uri": "GENEPIO:0101857" - } + }, + "protein_alias": [] }, "gene-NBT03_gp142": { "type": "gene", @@ -7820,7 +7958,8 @@ "protein_symbol": { "label": "Opg164 protein (MPOX)", "uri": "GENEPIO:0101858" - } + }, + "protein_alias": [] }, "gene-NBT03_gp143": { "type": "gene", @@ -7875,7 +8014,8 @@ "protein_symbol": { "label": "Opg165 protein (MPOX)", "uri": "GENEPIO:0101859" - } + }, + "protein_alias": [] }, "gene-NBT03_gp144": { "type": "gene", @@ -7930,7 +8070,8 @@ "protein_symbol": { "label": "Opg167 protein (MPOX)", "uri": "GENEPIO:0101861" - } + }, + "protein_alias": [] }, "gene-NBT03_gp145": { "type": "gene", @@ -7985,7 +8126,8 @@ "protein_symbol": { "label": "Opg170 protein (MPOX)", "uri": "GENEPIO:0101862" - } + }, + "protein_alias": [] }, "gene-NBT03_gp146": { "type": "gene", @@ -8040,7 +8182,8 @@ "protein_symbol": { "label": "Opg171 protein (MPOX)", "uri": "GENEPIO:0101863" - } + }, + "protein_alias": [] }, "gene-NBT03_gp147": { "type": "gene", @@ -8095,7 +8238,8 @@ "protein_symbol": { "label": "Opg172 protein (MPOX)", "uri": "GENEPIO:0101864" - } + }, + "protein_alias": [] }, "gene-NBT03_gp148": { "type": "gene", @@ -8150,7 +8294,8 @@ "protein_symbol": { "label": "Opg173 protein (MPOX)", "uri": "GENEPIO:0101865" - } + }, + "protein_alias": [] }, "gene-NBT03_gp149": { "type": "gene", @@ -8205,7 +8350,8 @@ "protein_symbol": { "label": "Opg174 protein (MPOX)", "uri": "GENEPIO:0101866" - } + }, + "protein_alias": [] }, "gene-NBT03_gp150": { "type": "gene", @@ -8260,7 +8406,8 @@ "protein_symbol": { "label": "Opg175 protein (MPOX)", "uri": "GENEPIO:0101867" - } + }, + "protein_alias": [] }, "gene-NBT03_gp151": { "type": "gene", @@ -8315,7 +8462,8 @@ "protein_symbol": { "label": "Opg176 protein (MPOX)", "uri": "GENEPIO:0101868" - } + }, + "protein_alias": [] }, "gene-NBT03_gp152": { "type": "gene", @@ -8370,7 +8518,8 @@ "protein_symbol": { "label": "Opg178 protein (MPOX)", "uri": "GENEPIO:0101869" - } + }, + "protein_alias": [] }, "gene-NBT03_gp153": { "type": "gene", @@ -8425,7 +8574,8 @@ "protein_symbol": { "label": "Opg180 protein (MPOX)", "uri": "GENEPIO:0101870" - } + }, + "protein_alias": [] }, "gene-NBT03_gp154": { "type": "gene", @@ -8480,7 +8630,8 @@ "protein_symbol": { "label": "Opg181 protein (MPOX)", "uri": "GENEPIO:0101871" - } + }, + "protein_alias": [] }, "gene-NBT03_gp155": { "type": "gene", @@ -8535,7 +8686,8 @@ "protein_symbol": { "label": "Opg185 protein (MPOX)", "uri": "GENEPIO:0101872" - } + }, + "protein_alias": [] }, "gene-NBT03_gp156": { "type": "gene", @@ -8590,7 +8742,8 @@ "protein_symbol": { "label": "Opg187 protein (MPOX)", "uri": "GENEPIO:0101873" - } + }, + "protein_alias": [] }, "gene-NBT03_gp157": { "type": "gene", @@ -8645,7 +8798,8 @@ "protein_symbol": { "label": "Opg188 protein (MPOX)", "uri": "GENEPIO:0101874" - } + }, + "protein_alias": [] }, "gene-NBT03_gp158": { "type": "gene", @@ -8700,7 +8854,8 @@ "protein_symbol": { "label": "Opg189 protein (MPOX)", "uri": "GENEPIO:0101875" - } + }, + "protein_alias": [] }, "gene-NBT03_gp159": { "type": "gene", @@ -8755,7 +8910,8 @@ "protein_symbol": { "label": "Opg190 protein (MPOX)", "uri": "GENEPIO:0101876" - } + }, + "protein_alias": [] }, "gene-NBT03_gp160": { "type": "gene", @@ -8810,7 +8966,8 @@ "protein_symbol": { "label": "Opg191 protein (MPOX)", "uri": "GENEPIO:0101877" - } + }, + "protein_alias": [] }, "gene-NBT03_gp161": { "type": "gene", @@ -8865,7 +9022,8 @@ "protein_symbol": { "label": "Opg192 protein (MPOX)", "uri": "GENEPIO:0101878" - } + }, + "protein_alias": [] }, "gene-NBT03_gp162": { "type": "gene", @@ -8920,7 +9078,8 @@ "protein_symbol": { "label": "Opg193 protein (MPOX)", "uri": "GENEPIO:0101879" - } + }, + "protein_alias": [] }, "gene-NBT03_gp163": { "type": "gene", @@ -8975,7 +9134,8 @@ "protein_symbol": { "label": "Opg195 protein (MPOX)", "uri": "GENEPIO:0101880" - } + }, + "protein_alias": [] }, "gene-NBT03_gp164": { "type": "gene", @@ -9029,7 +9189,8 @@ "protein_symbol": { "label": "Opg197 protein (MPOX)", "uri": "GENEPIO:0101881" - } + }, + "protein_alias": [] }, "gene-NBT03_gp165": { "type": "gene", @@ -9084,7 +9245,8 @@ "protein_symbol": { "label": "Opg198 protein (MPOX)", "uri": "GENEPIO:0101882" - } + }, + "protein_alias": [] }, "gene-NBT03_gp166": { "type": "gene", @@ -9139,7 +9301,8 @@ "protein_symbol": { "label": "Opg199 protein (MPOX)", "uri": "GENEPIO:0101883" - } + }, + "protein_alias": [] }, "gene-NBT03_gp167": { "type": "gene", @@ -9194,7 +9357,8 @@ "protein_symbol": { "label": "Opg200 protein (MPOX)", "uri": "GENEPIO:0101884" - } + }, + "protein_alias": [] }, "gene-NBT03_gp168": { "type": "gene", @@ -9249,7 +9413,8 @@ "protein_symbol": { "label": "Opg204 protein (MPOX)", "uri": "GENEPIO:0101885" - } + }, + "protein_alias": [] }, "gene-NBT03_gp169": { "type": "gene", @@ -9304,7 +9469,8 @@ "protein_symbol": { "label": "Opg205 protein (MPOX)", "uri": "GENEPIO:0101886" - } + }, + "protein_alias": [] }, "gene-NBT03_gp170": { "type": "gene", @@ -9359,7 +9525,8 @@ "protein_symbol": { "label": "Opg208 protein (MPOX)", "uri": "GENEPIO:0101887" - } + }, + "protein_alias": [] }, "gene-NBT03_gp171": { "type": "gene", @@ -9414,7 +9581,8 @@ "protein_symbol": { "label": "Opg209 protein (MPOX)", "uri": "GENEPIO:0101888" - } + }, + "protein_alias": [] }, "gene-NBT03_gp172": { "type": "gene", @@ -9469,7 +9637,8 @@ "protein_symbol": { "label": "Opg210 protein (MPOX)", "uri": "GENEPIO:0101889" - } + }, + "protein_alias": [] }, "gene-NBT03_gp173": { "type": "gene", @@ -9524,7 +9693,8 @@ "protein_symbol": { "label": "Opg005 protein (MPOX)", "uri": "GENEPIO:0101890" - } + }, + "protein_alias": [] }, "gene-NBT03_gp174": { "type": "gene", @@ -9576,7 +9746,8 @@ "protein_symbol": { "label": "Opg016 protein (MPOX)", "uri": "GENEPIO:0101891" - } + }, + "protein_alias": [] }, "gene-NBT03_gp175": { "type": "gene", @@ -9629,7 +9800,8 @@ "protein_symbol": { "label": "Opg015 protein (MPOX)", "uri": "GENEPIO:0101723" - } + }, + "protein_alias": [] }, "gene-NBT03_gp176": { "type": "gene", @@ -9684,7 +9856,8 @@ "protein_symbol": { "label": "Opg003 protein (MPOX)", "uri": "GENEPIO:0101722" - } + }, + "protein_alias": [] }, "gene-NBT03_gp177": { "type": "gene", @@ -9739,7 +9912,8 @@ "protein_symbol": { "label": "Opg002 protein (MPOX)", "uri": "GENEPIO:0101721" - } + }, + "protein_alias": [] }, "gene-NBT03_gp178": { "type": "gene", @@ -9794,7 +9968,8 @@ "protein_symbol": { "label": "Opg001 protein (MPOX)", "uri": "GENEPIO:0101720" - } + }, + "protein_alias": [] }, "INTERGENIC": { "type": "INTERGENIC", From 179844e635dbdac2dc2541ef5c48383eac3c4f9f Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 14:03:17 -0700 Subject: [PATCH 065/161] add indent to fix bug --- bin/functional_annotation.py | 20 ++++++++++---------- 1 file changed, 10 insertions(+), 10 deletions(-) diff --git a/bin/functional_annotation.py b/bin/functional_annotation.py index 617de7ac..7e008d2a 100755 --- a/bin/functional_annotation.py +++ b/bin/functional_annotation.py @@ -316,16 +316,16 @@ def write_tsv(dframe): dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "protein name"] = parent_protein_name dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "protein symbol"] = parent_protein_symbol parent_gene = GENE_PROTEIN_POSITIONS_DICT[entry]["gene"] - # get parent gene name and symbol from corresponding parent gene entry - for entry in GENE_PROTEIN_POSITIONS_DICT.keys(): - if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="gene" and (GENE_PROTEIN_POSITIONS_DICT[entry]["gene"]==parent_gene): - # extract gene names and symbols (ontology) from JSON entry - parent_gene_name = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_name"]["label"] - parent_gene_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_symbol"]["label"] - # add gene names and symbols to dataframe - dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene name"] = parent_gene_name - dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene symbol"] = parent_gene_symbol - dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene"] = GENE_PROTEIN_POSITIONS_DICT[entry]["gene"] + # get parent gene name and symbol from corresponding parent gene entry + for entry in GENE_PROTEIN_POSITIONS_DICT.keys(): + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="gene" and (GENE_PROTEIN_POSITIONS_DICT[entry]["gene"]==parent_gene): + # extract gene names and symbols (ontology) from JSON entry + parent_gene_name = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_name"]["label"] + parent_gene_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_symbol"]["label"] + # add gene names and symbols to dataframe + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene name"] = parent_gene_name + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene symbol"] = parent_gene_symbol + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene"] = GENE_PROTEIN_POSITIONS_DICT[entry]["gene"] # fill in mat_pep dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "mat_pep"] = mat_pep From 496ca377c82be5beb744f73530309b1ee80a21d7 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 15:08:25 -0700 Subject: [PATCH 066/161] replace 'pokay' with 'template' for generalizability --- bin/addfunctions2gvf.py | 24 ++++++++++++------------ 1 file changed, 12 insertions(+), 12 deletions(-) diff --git a/bin/addfunctions2gvf.py b/bin/addfunctions2gvf.py index b712532f..18f34dcc 100755 --- a/bin/addfunctions2gvf.py +++ b/bin/addfunctions2gvf.py @@ -37,8 +37,8 @@ def parse_args(): "troubleshooting purposes") return parser.parse_args() -# Function to add Pokay annotations to GVF file -def add_pokay_annotations(gvf, annotation_file): +# Function to add template annotations to GVF file +def add_template_annotations(gvf, annotation_file): # expand #attributes into columns to fill in separately gvf = separate_attributes(gvf) @@ -51,9 +51,9 @@ def add_pokay_annotations(gvf, annotation_file): # load functional annotations spreadsheet df = pd.read_csv(annotation_file, sep='\t', header=0) # replace spaces in column names with underscores to match the gvf attributes - pokay_columns = df.columns.tolist() - underscore_columns = [col.replace(" ", "_") for col in pokay_columns] - rename_dict = dict(zip(pokay_columns, underscore_columns)) + template_columns = df.columns.tolist() + underscore_columns = [col.replace(" ", "_") for col in template_columns] + rename_dict = dict(zip(template_columns, underscore_columns)) df = df.rename(columns=rename_dict) # if no author, fill with "UNKNOWN" df['author'] = df['author'].fillna('UNKNOWN') @@ -144,12 +144,12 @@ def add_pokay_annotations(gvf, annotation_file): gvf = gvf[~gvf['#seqid'].astype(str).str.contains("#")] # add functional annotations - pokay_annotated_gvf = add_pokay_annotations(gvf, args.functional_annotations) + template_annotated_gvf = add_template_annotations(gvf, args.functional_annotations) # add pragmas to df, then save to .gvf # columns are now 0, 1, ... - final_gvf = pd.DataFrame(np.vstack([pokay_annotated_gvf.columns, - pokay_annotated_gvf])) + final_gvf = pd.DataFrame(np.vstack([template_annotated_gvf.columns, + template_annotated_gvf])) final_gvf = pragmas.append(final_gvf) filepath = args.outgvf # outdir + strain + ".annotated.gvf" print("Saved as: ", filepath) @@ -162,11 +162,11 @@ def add_pokay_annotations(gvf, annotation_file): # functional_annotations) to a .tsv file # create mask to find which rows do not have a functional annotation - notinPokay_mask = pokay_annotated_gvf["#attributes"].str.contains("measured_variant_functional_effect=;") + notintemplate_mask = template_annotated_gvf["#attributes"].str.contains("measured_variant_functional_effect=;") # extract all mutation names from #attributes column - names = pd.Series(pokay_annotated_gvf["#attributes"].str.findall('(?<=original_mutation_description=)(.*?)(?=;)').str[0]) - # get unique mutation names not in Pokay - unmatched_names = pd.Series(names[notinPokay_mask].unique()) + names = pd.Series(template_annotated_gvf["#attributes"].str.findall('(?<=original_mutation_description=)(.*?)(?=;)').str[0]) + # get unique mutation names not in template + unmatched_names = pd.Series(names[notintemplate_mask].unique()) # save unmatched names to file if unmatched_names.shape[0] != 0: unmatched_names.to_csv(args.names, sep='\t', From a214a3466e566ba509ab7eb9be5ade70c48cd677 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 15:44:51 -0700 Subject: [PATCH 067/161] Rename functional annotation script --- bin/{functional_annotation.py => convert_pokay_to_virusmvp.py} | 0 1 file changed, 0 insertions(+), 0 deletions(-) rename bin/{functional_annotation.py => convert_pokay_to_virusmvp.py} (100%) diff --git a/bin/functional_annotation.py b/bin/convert_pokay_to_virusmvp.py similarity index 100% rename from bin/functional_annotation.py rename to bin/convert_pokay_to_virusmvp.py From 3ed971294e76f0f0e48fbabe14a0591d73b6fde0 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 16:51:19 -0700 Subject: [PATCH 068/161] take 'doi:' off saved dois --- bin/convert_pokay_to_virusmvp.py | 1 + 1 file changed, 1 insertion(+) diff --git a/bin/convert_pokay_to_virusmvp.py b/bin/convert_pokay_to_virusmvp.py index 7e008d2a..16473a33 100755 --- a/bin/convert_pokay_to_virusmvp.py +++ b/bin/convert_pokay_to_virusmvp.py @@ -407,4 +407,5 @@ def write_tsv(dframe): ###TO DO: modify dois2pmcids.sh to take the whole TSV as input and add PMIDs directly to the TSV to streamline this if args.save_dois != None: dois = merged_dataFrame[merged_dataFrame["DOI"]!=''].drop_duplicates(subset='DOI') + dois["DOI"] = dois["DOI"].str.replace("doi:", "", regex=False) dois["DOI"].to_csv(args.save_dois, header=False, index=False) \ No newline at end of file From 673ad82df3e40a9192e693755cfee723b0c5ce2e Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 17:08:03 -0700 Subject: [PATCH 069/161] add definitely the latest version --- ...kay_functionalAnnotation_SARSCoV2_v3.0.tsv | 1900 +++++++++++++++++ 1 file changed, 1900 insertions(+) create mode 100644 assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v3.0.tsv diff --git a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v3.0.tsv b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v3.0.tsv new file mode 100644 index 00000000..ccb13efb --- /dev/null +++ b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v3.0.tsv @@ -0,0 +1,1900 @@ +organism reference accession reference database name nucleotide position original mutation description nucleotide mutation amino acid mutation amino acid mutation alias gene name gene symbol protein name protein symbol measured variant functional effect inferred variant functional effect viral life cycle functional effect measured variant functional effect description CVX code DrugBank Accession Number Antibody Registry ID author publication year URL DOI PMID peer review status curator mutation functional annotation resource +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) viral load This mutant causes a 0.41x fold change in the infectious virus production rate. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has a 0.66x fold change in EC50 value with Remdesivir. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has an inhibition rate of virus production by Remdesivir of 0.80. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has a 0.27x fold change in EC50 value with Remdesivir. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has an inhibition rate of virus production by Remdesivir of 0.78. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) viral load This mutant causes a 0.48x fold change in the infectious virus production rate. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.526 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for 6 convalescent sera." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.8x reduction in IC50 serum dilution concentration for 6 convalescent sera." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,22992,23012,23664 L5F,S477N,E484K,A701V NC_045512.2:g.13C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 114 test-positive were Iota. Two dose vaccine efficacy against Iota was 95.7 (81.7-99.0%), one dose VE was 88.8 (0.7-98.7)%. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,25186 L5F,Q1208H NC_045512.2:g.13C>T,NC_045512.2:g.3624G>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Gln1208His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Four of the convalescent sera tested showed 4-fold or greater improvement in neutralization efficiency. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21587 P9S NC_045512.2:g.25C>T YP_009724390.1:p.Pro9Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2M28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21597 S12F NC_045512.2:g.35C>T YP_009724390.1:p.Ser12Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects A variant in low % circulation, predicted to have a similar effect to the experimentally verified S12P, which introduces a new signal peptide, altering cleavage to occur between residues C15 and V16, thereby eliminating the C15-C136 disulfide bond – similarly to escape mutants at positions C15 and C136. This in turn decreases to varying degrees N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600 S13I NC_045512.2:g.38G>T YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The S13I mutation dampened binding of 5 mAbs and abrogated binding of 5 additional mAbs out of 11 neutralizing mAbs evaluated. Predicted to shift the signal peptide cleavage site from S13-Q14 to C15-V16, which can affect NTD conformation. PG: in saying S12F does not shift the signal peptide nor affect mAb binding, this manuscript appears to contradict the text of McCallum et al.'s earlier 2021 manuscript stating that S12F *does* affected some mAb binding via putative signal peptide shift. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018 S13I,W152C NC_045512.2:g.38G>T,NC_045512.2:g.456G>T YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The B.1.427/B.1.429 S13I/W152C NTD did not bind to any NTD-directed neutralizing mAbs, which are known to target a single antigenic site (antigenic site i), whereas binding of the non-neutralizing S2L20 mAb to the NTD antigenic site iv was not affected by any mutants, confirming proper retention of folding. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Antibody neutralization assays showed 6.7-fold resistance against 7/8 convalescent plasma. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Swab samples N/NP viral RNA is approximately 2-fold higher in B.1.427/B.1.429 than in non-variant viruses. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 9 plasma collected 15 to 28 days after early 2020 infections, neutralization reduced 4.9-fold for B.1.427/B.1.429 compared to wildtype (D614G). In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.427/B.1.429 pseudotyped virus, as well as WT and other VOCs. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using HIV pseudotype: Neutralization potency of 11 Moderna mRNA1273-elicited plasma (7-27 days post-2nd dose) was reduced ~2.8-fold compared to wildtype (D614G) S. It was reduced ~4-fold in 14 Pfizer/BioNtech BNT162b2-elicited plasma (7-27 days post-2nd dose). Using VSV pseudotype: we observed a 3-fold average reduction of Pfizer/BioNtech BNT162b2-elicited plasma neutralizing activity. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.249 (1.7-fold). Neutralization against 10 convalescent plasma was somewhat poorer (3.1-fold). Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 14 of 34 RBD-specific mAbs showed reduced neutralization to the B.1.427/B.1.429 variant pseudotype. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility "Lineages bearing these spike mutations comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the ""California"" or ""West Coast"" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI:1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020." Peng 2021 https://doi.org/10.1093/cid/ciab283 doi:10.1093/cid/ciab283 33788923 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.427/429 reduced 2.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 6 of 11 (55%) vaccine recipients (Moderna or Pfizer), showed 2x reduction in neutralization to a B.1.429 lineage virus. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 2.7x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 2.3x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403,25135 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G,K1191N NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3573G>T YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys1191Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for CAL.20C (B.1.429), and a slight decrease in CD8+ percentage (p=0.0201) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21604,21604 Q14H,Q14H NC_045512.2:g.42G>C,NC_045512.2:g.42G>T YP_009724390.1:p.Gln14His,YP_009724390.1:p.Gln14His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21605 C15R NC_045512.2:g.43T>C YP_009724390.1:p.Cys15Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21606 C15F NC_045512.2:g.44G>T YP_009724390.1:p.Cys15Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates neutralization by N-terminal-domain-targeting mAbs 4-19. Impairs neutralization by N-terminal-domain-targeting mAbs 4A8 and 2-17. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggetsing that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132 L18F,T20N,P26S,D138Y,R190S NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "The neutralization titer of NTD-binding mAb159 was 133-fold reduced on P.1 compared to Victoria (~wild type), with only 64% neutralization at 10 μg/mL. Residues 20, 18, and 138 form a cluster underlying the 245–259 loop, which inserts into a groove between the light and heavy chains of Fab 159. In addition, the N-terminal residues preceding residue 18 interact with the antibody and may be perturbed. Given that there is likely a single supersite (""i"") for potent NTD-binding antibodies, the binding of many of these are likely affected. Using 20 potent (primaruly anti-RBD) antibodies, neutralization was measured by a focus reduction neutralization test (FRNT) and compared with neutralization of Victoria (~wild type) and variants B.1.1.7 and B.1.351. Compared to Victoria neutralization by the mAbs was significantly impacted by P.1, with 12/20 showing > 10-fold reduction in FRNT50 titer and a number showing complete knockout of activity. The results with P.1 showed a greater impact compared to B.1.1.7 but were, as expected, similar to those with B.1.351." Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Amongst RBD-targeting Emergency Use Authorized monoclonal antibody treatments CB6, LY-CoV555 and REGN10933 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1, but REGN10987 activity remains strong. RBD-targeting monoclonal antibodies 2-15 and C121 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. N terminal domain targeting monoclonal antibodies 5-7, 4-8, 4-18 and 2-17 have abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 33688656 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 12 Moderna vaccinee sera 15 days post second dose (43 days since first vaccination), an average 2.8x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 4.8x decrease against the full P.1 type vs WA-1 was observed, though overall with a higher ID50 reciprocal value. In 10 Pfizer vaccinee sera 7 days or more post second dose (28 days or more since first vaccination), an average 2.2x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.8x decrease against the full P.1 type vs WA-1 was observed, with similar variant ID50 reciprocal value. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 33688656 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure CryoEM reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the “up” position. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 33688656 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In convalescent sera one month or more post-infection in Spring 2020, an average 6.5x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.4x decrease against the full P.1 type vs WA-1 was observed, with better full P.1 ID50 reciprocal value compared to the 10-mutation model. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 33688656 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection After a 128 day interval, a patient in Sao Paulo State, Brazil reinfected with P.1 (first episode likely predates P.1 emergence). Both cases were fairly mild (difficulty breathing, tiredness, dizziness and fatigue). Malta Romano 2021 https://doi.org/10.1590/S1678-9946202163036 doi:10.1590/S1678-9946202163036 33909850 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Gamma (P.1) variant is 0.6x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 3.0x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 4.1x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 349 test-positive were Gamma. Two dose vaccine efficacy against Gamma was 95.5 (90.9-97.8%), one dose VE was 74.2 (43.8-88.1%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Three healthcare workers (29-50yo) had confirmed P.1 [Gamma] re-infection in the Amazonas region of Brazil 3-9 months after initial infection from viruses with distinct lineage from P.1, but mild symptoms upon re-infection and evidence for infectiousness during re-infection. Naveca 2021 https://doi.org/10.21203/rs.3.rs-318392/v1 doi:10.21203/rs.3.rs-318392/v1 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~6x cleavage of S2 relative to WA1 (D614G) wildtype by Gamma variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but H655Y is upstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was slightly lower against B.1.1.248 variant constellation in sera tested from most of the 15 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped P.1 virus has reduced neutralization activity vs wild type: 6.7x (30 sera Pfizer median 9 days post 2nd dose) and 4.5x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Unlike wild type or B.1.1.7, P.1 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. Montagutelli 2021 https://doi.org/10.1101/2021.03.18.436013 doi:10.1101/2021.03.18.436013 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.248 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07. B.1.1.248 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.7 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0039 for mild resistance. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.248 variant constellation in 10 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples, P=0.0020. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 16.6% in this B.1.1.248 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 33972942 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed. Andrade 2021 https://doi.org/10.1101/2021.04.14.439719 doi:10.1101/2021.04.14.439719 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed. Andrade 2021 https://doi.org/10.1101/2021.04.14.439719 doi:10.1101/2021.04.14.439719 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Among 46,884 HCWs in Manaus, Brazil vaccinated with at least one dose of CoronaVac, a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%; 95% CI, 11.3 - 71.4) in the odds of symptomatic SARS-CoV-2 infection was observed during the period 14 days or more after receiving the first dose. Estimated vaccine effectiveness of at least one dose against any SARS-CoV-2 infection was 35.1% (95% CI, −6.6 - 60.5) in the same time period. Hitchlings 2021 https://doi.org/10.1101/2021.04.07.21255081 doi:10.1101/2021.04.07.21255081 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.15x *increase* in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Neutralizing antibodies that were generated following a mild infection with SARS-CoV-2 B.1.128 were effective in vitro, and likely protective, against the SARS-CoV-2 P.1. variant in the majority of individuals based on 60 convalescent sera tested. Mendes-Correa 2021 https://doi.org/10.1101/2021.05.11.21256908 doi:10.1101/2021.05.11.21256908 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding VSV pseudotype P.1 showed 4.8-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections). Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking VSV pseudotype P.1 showed slight decrease in cell entry relative to wild type in 262T and 263T-ACE2 (kidney) cell lines. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness VSV pseudotype P.1 entry mediated by the S proteins of the P.1 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Cell fusion proficiency was slight impaired. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for P.1 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the P.1 variants used, using the most popular as a stand in] McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against P.1 at various time points using pseudovirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 85%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 256 for B.1.1.7 virus. Compare to somewhat stronger neutralization titer for wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion PBMCs of 11 mild COVID-19 patients collected 38-80 days after symptom onset were stimulated with the 15-mer peptide pools (w/ 10 residue overlaps) from the wholle viral proteome, showing no significant CD4+ cell count effect for P.1, and a slight increase in CD8+ percentage (p=0.0195) by Activation Induced Marker (AIM) assay (cellular immunity measurement). [in the text, this increase is not noted as signficant, even though p=0.05 is used elsewhere in the text as a signficance threshold] Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness P.1 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with Lilly mAb combination LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of P.1. There was also escape from neutralization of P.1 by REGN10933 (one of 2 in Regeneron's mAb cocktail) and a modest reduction in neutralization of P.1 by AstraZeneca's AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized P.1 with all reaching a plateau at 100% neutralization; interestingly, ADG30 showed a slight increase of neutralization of P.1. S309 Vir was largely unaffected, although for several viruses, including P.1, the antibody failed to completely neutralize, conceivably reflecting incomplete glycosylation at N343, since the sugar interaction is key to binding of this antibody. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The relative transmissibility of P.1 estimated at the national level (Italy) varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. PG: variant list has been abbreviated due to mixed K417 bases in this lineage, potential miscalls of deletions Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21801,22206,22334,22600,22600,22810,22811,22812,22813,22813,22879,22881,22882,22882,22986,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D80A,D215G,W258R,R346S,R346S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,A475V,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.772T>C,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1424C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ala475Val,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments and mutations from variants of concern completely ablates neutralization in 19 of 21 convalescents plasma collected mean 1.3 months post infection. [actual Y145del from manuscript substituted with more common Y144del description] Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801 L18F,D80A NC_045512.2:g.52C>T,NC_045512.2:g.239A>C YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The L18F and D80A of the B.1.351 lineage lead to reconfiguration of the N-terminal segment despite the disulfide between Cys16 and Cys136 that partly anchors the N-terminal peptide. The most consequential changes are probably from the triple residue deletion... which causes a shift of the nearby loop 144-155 and must also reconfigure the adjacent disorder loop (residues 246-260), both of which form part of the neutralizing epitopes...bringing large changes in the antigenic surface in this region. Cai 2021 https://doi.org/10.1101/2021.04.13.439709 doi:10.1101/2021.04.13.439709 33880477 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The 501Y.V2 to first wave IC50 ratio ranged from 6 to 200-fold. Averaging across all 7 participant convalescent sera highlighted the dramatic decrease in sensitivity to neutralization of authentic 501Y.V2 variants. PG: I'm purposefully ignoring D614G and A701V as contributors Cele 2021 https://doi.org/10.1038/s41586-021-03471-w doi:10.1038/s41586-021-03471-w 33780970 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In human sera 8 weeks post-vaccination with INO-4800, a ~7-fold reduction in B.1.351 neutralization was observed. Andrade 2021 https://doi.org/10.1101/2021.04.14.439719 doi:10.1101/2021.04.14.439719 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike). Riddell 2021 https://doi.org/10.1101/2021.04.17.440246 doi:10.1101/2021.04.17.440246 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike). Riddell 2021 https://doi.org/10.1101/2021.04.17.440246 doi:10.1101/2021.04.17.440246 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pzifer vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1), but were all infected before 14 days post second vaccination. Kustin 2021 https://doi.org/10.1101/2021.04.06.21254882 doi:10.1101/2021.04.06.21254882 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Wu 2021 https://doi.org/10.1101/2021.04.13.439482 doi:10.1101/2021.04.13.439482 33880468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Wu 2021 https://doi.org/10.1101/2021.04.13.439482 doi:10.1101/2021.04.13.439482 33880468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Wu 2021 https://doi.org/10.1101/2021.04.13.439482 doi:10.1101/2021.04.13.439482 33880468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals (5/9) and recipients of a only a single dose of mRNA vaccine (10/11) – heterotypic neutralization dropped to negligible levels, particularly against B.1.351. Skelly 2021 https://doi.org/10.21203/rs.3.rs-226857/v1 doi:10.21203/rs.3.rs-226857/v1 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR22 molecule had a 1.57x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness B.1.351 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of B.1.351. There was also escape from neutralization of B.1.351 by REGN10933 and a modest reduction in neutralization of B.1.351 by AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized B.1.351. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.054x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 8 for B.1.351 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Sera from individuals who have been infected with Delta does not have strong neutralising activity against Beta. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Beta neutralizing antibodies is 0.803x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.351. We observed an increase (relative to D614G) in binding of soluble ACE2 to B.1.351, and to a much gearter extent to B.1.1.7, which both carry the N501Y mutation (see Fig 3). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Pseudotype lentivirus for the full B.1.351 Spike variant list shows increase affinity for ACE2 as measured by IC50. This is in contrast to B.1.1.7 which showed no major change, indicating that the shared N501Y mutation is the driver of affinity change, attentuated in the B.1.1.7 mutatioon set, but maintained in the B.1.351 lineage. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 6.3x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Beta Variant B.1.351 RBD significantly better than w.t. SARS-CoV-2 RBD. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.07x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed for B.1.351 a CD4+ cell count decrease (29%, p=0.00063) as well as CD8+ (33%, p=0.0016) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera). Madhi 2021 https://doi.org/10.1056/NEJMoa2102214 doi:10.1056/NEJMoa2102214 33725432 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against Beta. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Encouragingly, we find that the majority of T cell responses in recipients of two doses of the BNT162b2 vaccine are generated by epitopes that are invariant between the [wildtype] and two of the current variants of concern (B.1.1.7 and B.1.351). In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals and recipients of a only a single dose of mRNA vaccine – heterotypic neutralization dropped to negligible levels, particularly against B.1.351. Skelly 2021 https://doi.org/10.21203/rs.3.rs-226857/v1 doi:10.21203/rs.3.rs-226857/v1 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 8.2x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The neutralizing activity of 16/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.351, with similar results for the live virus. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Beta neutralizing antibodies is 0.899x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.351 v2 virus has reduced neutralization activity vs wild type: 41.2x (30 sera Pfizer median 9 days post 2nd dose) and 20.8x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021 https://doi.org/10.1056/NEJMoa2103055 doi:10.1056/NEJMoa2103055 33951374 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v2 reduced 7.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type). Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021 https://doi.org/10.1056/NEJMoa2103055 doi:10.1056/NEJMoa2103055 33951374 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing] Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing] Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera). Madhi 2021 https://doi.org/10.1056/NEJMoa2102214 doi:10.1056/NEJMoa2102214 33725432 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.351 sample. Contrast this with 1.4-fold reduction for just the pseudovirus combination of ""key"" B.1.351 mutations K417N+E484K+N501Y. WA1 and B.1.351 FRNT50 titers correlated weakly at the individual level, with some individual’s serum potently neutralizing WA1 while having FRNT50 for B.1.351 below the assay limit of detection (1:20)." Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing] Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.351 pseudotyped virus model ablates neutralization by RBD-directed mAbs CB6, 4-20, 2-4, 2-43, 910-30, 2-302-15, LY-Cov555, C121. B.1.351 pseudotyped virus model severely impairs neutralization by RBD-directed mAb 1-20. B.1.351 pseudotyped virus model impairs neutralization by RBD-directed mAb REGN10933. B.1.351 pseudotyped virus model ablates neutralization by N-terminal-domain-directed mAbs 5-24, 4-8, 4A8, 4-19. B.1.351 pseudotyped virus model severely impairs neutralization by N-terminal-domain-directed mAb 2-17. B.1.351 pseudotyped virus model impairs neutralization by N-terminal-domain-directed mAb 5-7. PG: Live virus data for the same mAbs is similar, but 1-20 becomes severally impaired, REGN10933 activity is ablated, and Brii-196 becomes impaired. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type). Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 3.2x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type). Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy [Contrary to how this paper has been cited, Voysey et al. do NOT show evidence of decreased effectiveness of ChAdOx1 (AstraZeneca) against the South African B.1.351 lineage. Insufficient numbers reaching the primary study endpoint were available in that arm of the vaccine study to report any statistics from the South African participants. Additionally, the study period of the paper ended in November 2020, while the earliest reported case of this lineage is October (covariants.org), only becoming dominant by mid-November.] Voysey 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021 https://doi.org/10.1056/NEJMoa2103055 doi:10.1056/NEJMoa2103055 33951374 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021 https://doi.org/10.1056/NEJMoa2103055 doi:10.1056/NEJMoa2103055 33951374 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms had mean ~6x reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: while B.1.1.7 and D614G showed neutralization by nasal swab from only one different previously infected vacinee neutralizing at weeks 3 and 6, B.1.351 showed zero neutralization at either time point in any sample (and relatively impaired serum neutralization). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape A 1.8-fold drop in FRNT50 for B.1.351 was observed in 44 sera collected between 1 and 301 post-infection. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR16m molecule had a 0.036x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR16m molecule had a 99.7x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR16m molecule had a 6.7x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with all key mutations from B.1.351 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting some synergy between the mutations to decrease cell entry fitness (i.e. cell entry is liklely not the driver of this lineage's dominance). Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,23060,23061,23062,23063,22810,22811,22812,22813,22813,23012,23399,23401,23402,23403 L18F,D80A,D215G,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The most significant loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against authentic B.1.351 lineage virus (9.2-fold). Neutralization against 10 convalescent plasma was poorer (18.7x). Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks. Meister 2021 https://doi.org/10.1093/infdis/jiab260 doi:10.1093/infdis/jiab260 33993274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication] Ribas Freitas 2021 https://doi.org/10.1101/2021.04.13.21255281 doi:10.1101/2021.04.13.21255281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the Parana state of Brazil, patients aged 20-29 years experienced a tripling of their case fatality rate (CFR), from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling comparing February to January in 2021. Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil. [this is somewhat indirect evidence that assume greatly increasing proportion of P.1 cases in March (70%) compared to February, but the first official ID of P.1 in Parana state (Feb 16th) may be due to testing procedures rather than actual prevalence] Santos de Oliviera 2021 https://doi.org/10.1101/2021.03.24.21254046 doi:10.1101/2021.03.24.21254046 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication] Ribas Freitas 2021 https://doi.org/10.1101/2021.04.13.21255281 doi:10.1101/2021.04.13.21255281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication] Ribas Freitas 2021 https://doi.org/10.1101/2021.04.13.21255281 doi:10.1101/2021.04.13.21255281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22915,22916,22917,23060,23061,23062,23063,23521,23522,23524,23525 L18F,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 (Pfizer) vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains. Mallm 2021 https://doi.org/10.1101/2021.04.27.21254849 doi:10.1101/2021.04.27.21254849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1, Delta (B.1.617.2) shows mean 2.1x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Relative to B.1, Delta (B.1.617.2) shows 3.64x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,22915,22916,22917,23012,23399,23401,23402,23403 T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this lineage defining mutation combination from B.1.617.3 increased syncytium formation ~2.3x. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,22915,22916,22917,23012,23399,23401,23402,23403 T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this lineage defining mutation combination from B.1.617.3 conferred a ~11.8x drop in neutralization (NT50) [suggesting role for T19R and T95I in half the sera]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,22915,22916,22917,23012,23399,23401,23402,23403 T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this lineage defining mutation combination from B.1.617.3 conferred a ~4.5x infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,23399,23401,23402,23403 T19R,T95I,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22028,22915,22916,22917,23604,23399,23401,23402,23403,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,E156del,L452R,L452R,L452R,P681R,D614G,D614G,D614G,D614G,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.467_472del,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4.5x cleavage of S2 relative to WA1 (D614G) wildtype by Delta (B.1.617.2) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~3.5x for closely related Kappa B.1.617.1 also with P681R at the cleavage site). Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. [Mutation list in publication appears to contain a typo with R158del instead of R158G]" Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 4.0x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Modelling the Delta variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increased 11x relative to wild type (15.3 vs 1.4). [del ~157 truncated due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a coinfection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant. Liu 2021 https://doi.org/10.1101/2021.08.12.456173v3 doi:10.1101/2021.08.12.456173v3 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 2.6x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.020x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.10x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In primary human airway epithelial cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 1.9x relative to wild type (2.7 vs 1.4). This is the Delta variant with the P681R furin cleavage site mutation absent. [del ~157 truncated due to ambiguity] Liu 2021 https://doi.org/10.1101/2021.08.12.456173v3 doi:10.1101/2021.08.12.456173v3 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Plasma neutralizing activity was also assessed against SARS-CoV-2 Delta, Omicron BA.1, BA.2 and BA.4/5 variants using viruses pseudotyped with appropriate variant spikeproteins. Delta breakthrough infection resulted in 15-fold increased neutralizing titers. Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Plasma neutralizing activity in 49 participants was measured using HIV-1 pseudotyped with the 100 WT SARS-CoV-2 spike protein. Delta breakthrough infection resulted in 11-fold increased geometric mean half-maximal neutralizing titer (NT50). Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Delta neutralizing antibodies is 0.872x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Delta Variant B.1.617.2 RBD or w.t. SARS-CoV-2 RBD with nearly equal potency determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 507 pM for binding to the Delta B.1.617.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Delta neutralizing antibodies is 0.952x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy The incidence rate of Covid-19 during the Delta-dominant period (Jul-Aug 2021) was lower for late vaccinated (49.0/1000 person-years) [formerly placebo] versus early vaccinated (77.1/1000 person-years) participants in the Moderna mRNA-1273 Phase 3 trials, representing a 36.4% VE reduction (95% CI 17.1%-51.5%). There were fewer severe Covid-19 cases in the late group (6; 6.2/1000 person-years) than early (13; 3.3/1000 person-years), representing a 46.0% reduction (95% CI −52.4%-83.2%). Three Covid-19 related hospitalizations occurred with two resulting deaths in the early group. Baden 2021 https://doi.org/10.1101/2021.09.17.21263624 doi:10.1101/2021.09.17.21263624 34611666 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 34437521 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021 https://doi.org/10.15585/mmwr.mm7034e3 doi:10.15585/mmwr.mm7034e3 34437519 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.92x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Delta Molnupiravir (MK-4482) had ~4x fold drop. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role. Tang 2021 https://doi.org/10.1101/2021.08.11.21261885 doi:10.1101/2021.08.11.21261885 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). Chia 2021 https://doi.org/10.1101/2021.07.28.21261295 doi:10.1101/2021.07.28.21261295 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 34437521 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021 https://doi.org/10.15585/mmwr.mm7034e3 doi:10.15585/mmwr.mm7034e3 34437519 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role. Tang 2021 https://doi.org/10.1101/2021.08.11.21261885 doi:10.1101/2021.08.11.21261885 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021 https://doi.org/10.15585/mmwr.mm7034e3 doi:10.15585/mmwr.mm7034e3 34437519 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 34437521 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 34437521 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021 https://doi.org/10.15585/mmwr.mm7034e3 doi:10.15585/mmwr.mm7034e3 34437519 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role. Tang 2021 https://doi.org/10.1101/2021.08.11.21261885 doi:10.1101/2021.08.11.21261885 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). Chia 2021 https://doi.org/10.1101/2021.07.28.21261295 doi:10.1101/2021.07.28.21261295 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021 https://doi.org/10.15585/mmwr.mm7034e3 doi:10.15585/mmwr.mm7034e3 34437519 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 34437521 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 34437521 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death. 2021 https://doi.org/10.1503/cmaj.211248 doi:10.1503/cmaj.211248 34610919 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance. Twohig 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death. 2021 https://doi.org/10.1503/cmaj.211248 doi:10.1503/cmaj.211248 34610919 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance. Twohig 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death. 2021 https://doi.org/10.1503/cmaj.211248 doi:10.1503/cmaj.211248 34610919 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccination of health care workers in Delhi was started in early 2021, with the ChdOx-1 (Astra Zeneca) vaccine. Surveillance has suggested B.1.1.7 dominance in the Delhi area during early 2021, with growth of B.1.617 since March 2021. During the wave of infections during March and April an outbreak of SARS-CoV-2 was confirmed in 33 vaccinated staff members at a single tertiary centre (age 27-77 years). Sequencing revealed that 16/33 were B.1.617.2, with a range of other B lineage viruses including B.1.1.7 for the rest except one A lineage case. Importantly no severe cases were documented in this event. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Case 62541 cluster in Singapore included a fully vaccinated nurse 2 months post-vaccine [likely Pfizer based on dates and supply], and a doctor of unknown vaccine status. This cluster was caused by a B.1.617.2 virus [via crossreference to Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Denmark, for the period Jan 1 to Jun 27, 2021, Delta variant was associated with increased an risk ratio of 2.83 [95% CI 2.02–3.98] for hospitalization. Bager 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.2 aka Delta) showed a 2.34x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.89x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Delta (B.1.617.2) has an IC50 fold change of 46.5x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Delta (B.1.617.2) variant is 0.6x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Delta (B.1.617.2) has an IC50 fold change of 0.57x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Delta (B.1.617.2) has an IC50 fold change of 0.87x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Delta (B.1.617.2) has an IC50 fold change of 0.15x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,23399,23401,23402,23403 T19R,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21627 T22I NC_045512.2:g.65C>T YP_009724390.1:p.Thr22Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain, frequently observed in various human infection lineages, reduces the tropism of SARS-CoV-2 in F81 (cat kidney, Felis catus) and BHK-21 (golden hamster kidney, Mesocricetus auratus) cell line cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21648 T29I NC_045512.2:g.86C>T YP_009724390.1:p.Thr29Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21717,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23399,23401,23402,23403,23593,23593,24224 Q52R,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,D614G,D614G,D614G,D614G,Q677H,Q677H,F888L NC_045512.2:g.155A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.525 reduced 4.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21717,23012,23593,23593,24224 Q52R,E484K,Q677H,Q677H,F888L NC_045512.2:g.155A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The B.1.525 appears to have poor transmissibility when in competition with B.1.1.7 and other circulating strains in Denmark (early 2021). Albertsen 2021 https://www.covid19genomics.dk/2021-05-08_data-overview.html#b1525 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21752,21752 W64R,W64R NC_045512.2:g.190T>A,NC_045512.2:g.190T>C YP_009724390.1:p.Trp64Arg,YP_009724390.1:p.Trp64Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21759 H66R NC_045512.2:g.197A>G YP_009724390.1:p.His66Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent, especially on a D614 wildtype background. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Neutralization activity of almost all Moderna Phase 1 sera tested actually *increased*. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This deletion outside the receptor binding domain in pseudotyped VSV promoted the capacity of pseudotyped VSV to transduce black flying fox (Pteropus alecto) kidney PabKi.1 cells (17.8%) to a level twice that of human epithelial-like Huh-7 cells (9.8%) Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduces neutralization by structurally unmapped mAb COVA1-21 (cluster XI). Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization activity of almost all convalescent sera tested decreased ~2x. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence The delH69/V70 enhances viral infectivity, indicating its effect on virus fitness is independent to the N501Y RBM change [with which it is found in lineage B.1.1.7] Possibly arisen as a result of the virus evolving from immune selection pressure in infected individuals and possibly only one chronic infection in the case of lineage B.1.1.7. Kemp 2020 https://doi.org/10.1101/2020.12.14.422555 doi:10.1101/2020.12.14.422555 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding No notable change in neutralization efficiency, despite N439K by itself showing a ~2x decrease on average in 16 health workers' convalescent sera. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization activity of convalescent sera tested decreased ~2x with this B.1.1.7 pseudotyped virus. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron (a.k.a. B.1.1.529) Spike pseudotyped VSV and Vero E6 cells has somewhat reduced neutralization (2.7x) vs wild type with monoclonal antibody Sotrovimab (a.k.a. VIR-7831). [delins at 214 omitted for syntax compatibility] Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron breakthrough infection after 3-dose vaccination resulted in a further 3.5-fold and 2.9-fold increase of Omicron BA.1 and BA.2 neutralizing titers. Omicron BA.4/5 showed the highest neutralization resistance of all variants tested, resulting in low geometric mean neutralizing titers in plasma samples obtained after the second vaccine dose (NT50=72). Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron B.1.1.529 (BA.1) neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron (B.1.1.529 [BA.1]) have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Omicron variant and was used to determine neutralizing antibodytitres. There was a 114.84x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 6.61x fold increase in antibody response pre-reinfection. There was a 1194.9x fold increase in antibody response during reinfection. Shete 2022 https://doi.org/10.1101/2022.05.12.491584 doi:10.1101/2022.05.12.491584 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Omicron BA.1 variant is 1.0x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.1 has an IC50 fold change of 0.30x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 73 pM for binding to the Omicron B.1.1.529. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigms’ ACE-2 variant LVE/STR chimera binds to SARS-2 Omicron variant B.1.1.529 spike protein trimer with high affinity. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Omicron BA.1 has an IC50 fold change of 1.26x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Delta variant and was used to determine neutralizing antibodytitres. There was a 24.63x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 4.21x fold increase in antibody response pre-reinfection. There was a 39.27x fold increase in antibody response during reinfection. Shete 2022 https://doi.org/10.1101/2022.05.12.491584 doi:10.1101/2022.05.12.491584 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.1 has an IC50 fold change of 0.08x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Omicron BA.1 has an IC50 fold change of 0.38x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding All 10 individuals with 3 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 3319 NT50. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding All 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 729 NT50. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against B.1 variant and was used to determine neutralizing antibodytitres. There was a 6.76x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 2.06x fold increase in antibody response pre-reinfection. There was a 8.18x fold increase in antibody response during reinfection. Shete 2022 https://doi.org/10.1101/2022.05.12.491584 doi:10.1101/2022.05.12.491584 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.3 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.3 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was somewhat lower against B.1.1.7 in sera tested from most of the 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.7 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2489. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.1.7 sample. Contrast this with 1.3-fold reduction for just the pseudovirus combination of ""key"" B.1.1.7 mutation N501Y." Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild to modest decrease in infection rate amongst the cells, suggesting a net mild negative effect on human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing moderate decrease in infection rate amongst the cells, significantly lower than the deletion or Y453F alone, or their combination, suggesting a synergistic effect on poorer human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, much closer to D614G activity level than Y453F alone, suggesting compensatory effects between the deletion and the mutation in human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,23399,23401,23402,23403,25249,25249,25249 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,D614G,D614G,D614G,D614G,M1229I,M1229I,M1229I NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.298 virus has reduced neutralization activity vs wild type: 1.4x (30 sera Pfizer median 9 days post 2nd dose) and 1.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,25249,25249,25249 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells, markedly higher infectivity than either mutation alone, suggesting a synergistic net neutral effect on human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,25249,25249,25249 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Lentiviral pseudotyped with the key mutations from Mink Cluster 5 was neutralized more easily than D614G in 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,25249,25249,25249 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with all key mutations from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (~50%) decrease in infection rate amongst the cells, suggesting that this anthropozoonotic event is driven by other factors at the expense of human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.7+E484K reduced 2.8x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Compare with 1.2x reduction for B.1.1.7 without E484K. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization capacity GMT of 27 subjects' sera post-infection was markedly worse against B.1.1.7 + E484K than the lineage alone, with a 11.4x drop. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This mutation combination causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x). PG: these effects are laregly missing in the deletion-alone data Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." van Loon 2021 https://doi.org/10.1101/2021.04.15.21255389 doi:10.1101/2021.04.15.21255389 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." van Loon 2021 https://doi.org/10.1101/2021.04.15.21255389 doi:10.1101/2021.04.15.21255389 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence A higher proportion of cases infected with the B.1.1.7 variant were hypoxic on admission compared to other variants (70.0% vs 62.5%, p=0.029), in London between March 13th 2020 and February 17th 2021 (400 B.1.1.7 cases out of 1470 total sequenced). Snell 2021 https://doi.org/10.1101/2021.03.16.21253377 doi:10.1101/2021.03.16.21253377 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, moreso than this combination with the addition of P681H. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021 https://doi.org/10.1136/bmj.n1088 doi:10.1136/bmj.n1088 33985964 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) clinical indicators After adjusting for the age factor, in a prospective Chinese cohort study B.1.1.7 variant infection (compared to B.1.140) was the risk factor for C-reactive protein (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), Serum amyloid A (0.011, 5.031, [1.459, 17.354]), Creatine Kinase (0.034, 4.34, [0.05, 0.91]), CD4+ T lymphocyte (0.029, 3.31, [1.13, 9.71]), and Ground Glass Opacity (0.005, 5.418, [1.656, 17.729]) Song 2021 https://doi.org/10.1101/2021.05.04.21256655 doi:10.1101/2021.05.04.21256655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021 https://doi.org/10.1016/j.cmi.2021.05.007 doi:10.1016/j.cmi.2021.05.007 33984489 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021 https://doi.org/10.1136/bmj.n1088 doi:10.1136/bmj.n1088 33985964 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021 https://doi.org/10.1136/bmj.n1088 doi:10.1136/bmj.n1088 33985964 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021 https://doi.org/10.1016/j.cmi.2021.05.007 doi:10.1016/j.cmi.2021.05.007 33984489 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021 https://doi.org/10.1016/j.cmi.2021.05.007 doi:10.1016/j.cmi.2021.05.007 33984489 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021 https://doi.org/10.1136/bmj.n1088 doi:10.1136/bmj.n1088 33985964 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion). Marquez 2021 https://doi.org/10.1017/ice.2021.195 doi:10.1017/ice.2021.195 33934744 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Second infection in December 2020 with B.1.1.7 after April 2020 initial infection with B.2 in a 78-year-old man with a history of Type 2 diabetes mellitus, diabetic nephropathy on hemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnea, ischemic heart disease, with no history of immunosuppression. Harrington 2021 https://doi.org/10.1093/cid/ciab014 doi:10.1093/cid/ciab014 33421056 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM for binding to the Alpha B1.1.7. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Lessens the potency of mAbs COVA2-17 (~5x, similar to N501Y alone), COVA1-12 (~11x) and COVA1-21 (>100x), which do not compete allosterically." Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 1.7x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.7 pseudotyped virus model impairs binding by RBD-directed mAb 910-30. B.1.1.7 pseudotyped virus model abolishes N-terminal-domain-directed mAbs 5-24, 4-8, and 4A8. B.1.1.7 pseudotyped virus model impairs binding by N-terminal-domain-directed mAbs 2-17, 4-19, 5-7. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020. Possible reinfections were identified in 249 (0.7% [95% CI 0.6-0.8]) of 36509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Graham 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects ~20x resistence to mAb CQ038 by B.1.1.7 pseudotyped virus Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Alpha Variant B.1.1.7 RBD significantly better than GenScript IgG FL18-740 w.t. ACE-2 mAB. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.1.7. We observed a dramatic increase (relative to D614G) in binding of soluble ACE2 to B.1.1.7, and to a lesser extent to B.1.351, which both carry the N501Y mutation (see Fig 3). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion). Marquez 2021 https://doi.org/10.1017/ice.2021.195 doi:10.1017/ice.2021.195 33934744 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%). Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) aerosolization Alpha variant cases in a large campus study showed fine-aerosol shedding amongst unmasked participants remained significantly greater for alpha variant infections (18-fold, 95% CI, 3.4 to 92-fold) after adjusting for the increased viral RNA in MTS and saliva, the number of coughs during sampling sessions, and symptom. After controlling for the effect of masks and numbers of coughs during sampling, alpha variant infection was associated with a 100-fold (95% CI, 16 to 650-fold) increase in coarse- and a 73-fold (95% CI, 15 to 350-fold) increase in fine-aerosol RNA shedding. Adenaiye 2021 https://doi.org/10.1093/cid/ciab797 doi:10.1093/cid/ciab797 34519774 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~2.5x cleavage of S2 relative to WA1 (D614G) wildtype by Alpha variant variant as measured by mass spectrometry of Vero-TMPRSS culture. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events First documented cases of domestic cat and dog infections with the B.1.1.7 strain. Hamer 2021 https://doi.org/10.1111/tbed.14122 doi:10.1111/tbed.14122 33955193 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 2.6x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the 47D10. Alpha (B.1.1.7) has an IC50 fold change of 0.40x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks. Meister 2021 https://doi.org/10.1093/infdis/jiab260 doi:10.1093/infdis/jiab260 33993274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively. Schuit 2021 https://doi.org/10.1093/infdis/jiab171 doi:10.1093/infdis/jiab171 33822064 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively. Schuit 2021 https://doi.org/10.1093/infdis/jiab171 doi:10.1093/infdis/jiab171 33822064 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.44x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure CryoEM analysis of B.1.1.7 demonstrates an increased propensity for 'up', receptor accessible conformation of the Spike protein trimer. Cai 2021 https://doi.org/10.1101/2021.04.13.439709 doi:10.1101/2021.04.13.439709 33880477 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralizing antibody titers of 2/20 (10%) samples showed >10x reduction (sera collected ~1mo post Jan 2020 first wave in China). Neutralizing antibody titers of 8/20 samples (40%) decreased below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China). Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The sera of 16 individuals with time course collection was evaulated against VSV pseudotypes: neutralized D614G at week 2, whereas B.1.1.7 started to be neutralized at week 3, although less efficiently than D614G. B.1.1.7 and D614G strains were similarly neutralized at week 4 (1 week after booster dose). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021 https://doi.org/10.1136/bmj.n1088 doi:10.1136/bmj.n1088 33985964 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 33972942 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We observed a sharp decline in cases when ∼50% of the elderly population was 2 weeks beyond their first vaccination dose and at a time point during which the B.1.1.7 variant gained transmission dominance. In support of this finding, it was suggested that, after the first vaccination dose, more than 70% of patients develop neutralization antibodies,15 and the vaccine efficiency can reach 85%. Munitz 2021 https://doi.org/10.1016/j.xcrm.2021.100264 doi:10.1016/j.xcrm.2021.100264 33899031 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 33972942 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Live virus was tested ex vivo in reconstituted brochial epithelium, and out competed wild type. Touret 2021 https://doi.org/10.1101/2021.03.22.436427 doi:10.1101/2021.03.22.436427 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.39x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization assays of B.1.1.7 virus showed a reduction of 2.5-fold (14 days post 2nd dose AstraZeneca, n=15), 2.1-fold (28 days post 2nd dose AstraZeneca, n=10), and 3.3-fold (7-17 days post 2nd dose Pfizer-BioNTech, n=25). [D1119H was included in the original paper, assumed typographical error and changed to D1118H] Supasa 2021 https://doi.org/10.1016/j.cell.2021.02.033 doi:10.1016/j.cell.2021.02.033 33743891 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 1 (B.1.1.7) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2. Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021 https://doi.org/10.1016/j.cmi.2021.05.007 doi:10.1016/j.cmi.2021.05.007 33984489 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape NTD-specific nAbs showed a substantial (3-450x) decrease in neutralization potency against the recently reported highly transmissible B.1.1.7 variant of concern, whereas RBD-specific nAbs were either unaffected or showed lower decreases in potency. Graham 2021 https://doi.org/10.1016/j.immuni.2021.03.023 doi:10.1016/j.immuni.2021.03.023 33836142 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Modelling the Alpha variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 3.9x relative to wild type (5.4 vs 1.4). This is less efficient than Delta (11x vs wildtype using a P681R mutation instead). [del ~144 changed due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a co-infection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant. Liu 2021 https://doi.org/10.1101/2021.08.12.456173v3 doi:10.1101/2021.08.12.456173v3 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.7 virus has reduced neutralization activity vs wild type: 2.1x (30 sera Pfizer median 9 days post 2nd dose) and 2.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Note that Y145del was actually noted in the paper as the effect of their DNA construct, but this is equivalent at the protein level to the more commonly annotated Y144del. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Alpha (B.1.1.7) variant is 1.0x fold the wildtype in 42 COVI. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Alpha Molnupiravir (MK-4482) had ~2.75x fold drop. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy NVX-CoV2373 [Novavax] vaccine in phase 3 trial was 89.7% (95% CI, 80.2-94.6) effective in preventing COVID-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8-99.5) and 86.3% (71.3-93.5) against the prototype strain and B.1.1.7 variant, respectively. Heath 2021 https://doi.org/10.1101/2021.05.13.21256639 doi:10.1101/2021.05.13.21256639 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Alpha (B.1.1.7) has an IC50 fold change of 1.19x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.1.7 lineage effectiveness was observed as 29.5% (95% CI [22.9,35.5]) against infection, and 54.1% against severe/critical/fatal disease (95% CI [26.1-71.9]). Two weeks or more after 2nd dose, effectiveness climbed to 89.5% [85.9,92.3] against infection, and 100% against severe/critical/fatal disease (95% CI [81.7,100]). Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24506 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,S982A NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Lilly's LY-CoV16 showed marked reduction in neutralization of B.1.1.7. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Sera neutralized the B1.1.7 isolate with a lower potency (2-fold; 95% CL: 1.5 – 3-fold), and those with the lowest homotypic neutralizing potency had undetectable heterotypic potency (2/25). Skelly 2021 https://doi.org/10.21203/rs.3.rs-226857/v1 doi:10.21203/rs.3.rs-226857/v1 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23709,23604,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,T716I,P681H,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific replication effects In this report, by using a lower infectious dose, we demonstrate that B.1.1.7 (cultured sample Hong Kong/HKPU-00015/2021) exhibits higher infectivity and/or replication efficiency in the nasal epithelium. (Hamster model of infection) Mok 2021 https://doi.org/10.1101/2021.04.19.440414 doi:10.1101/2021.04.19.440414 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021 https://doi.org/10.48550/arXiv.2104.05560 doi:10.48550/arXiv.2104.05560 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021 https://doi.org/10.1101/2021.02.24.21251989 doi:10.1101/2021.02.24.21251989 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021 https://doi.org/10.1038/s41586-021-03426-1 doi:10.1038/s41586-021-03426-1 33723411 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. Graham 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively. Roquebert 2021 https://doi.org/10.1101/2021.03.19.21253971 doi:10.1101/2021.03.19.21253971 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. Graham 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio 341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). Frampton 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021 https://doi.org/10.1101/2021.02.24.21251989 doi:10.1101/2021.02.24.21251989 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies. Muik 2021 https://doi.org/10.1126/science.abg6105 doi:10.1126/science.abg6105 33514629 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies. Muik 2021 https://doi.org/10.1126/science.abg6105 doi:10.1126/science.abg6105 33514629 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The mortality hazard ratio associated with infection with [B.1.1.7] compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community (54906 matched pairs of participants who tested positive for SARS-CoV-2 in pillar 2 between 1 October 2020 and 29 January 2021). In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases. Challen 2021 https://doi.org/10.1136/bmj.n579 doi:10.1136/bmj.n579 33687922 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." Couzens 2021 https://doi.org/10.1101/2021.04.02.21254832 doi:10.1101/2021.04.02.21254832 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021 https://doi.org/10.1101/2021.02.24.21251989 doi:10.1101/2021.02.24.21251989 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021 https://doi.org/10.1038/s41586-021-03426-1 doi:10.1038/s41586-021-03426-1 33723411 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021 https://doi.org/10.48550/arXiv.2104.05560 doi:10.48550/arXiv.2104.05560 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021 https://doi.org/10.48550/arXiv.2104.05560 doi:10.48550/arXiv.2104.05560 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 20/29 sera after the first dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 variant of 3.2 ± 5.7. After the second dose, the GMT was markedly increased compared with the first-dose titres, with a fold change of 1.9 ± 0.9 (mean ± s.d.). Neutralization GMT of 27 subjects post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization capacity GMT of 27 subjects' sera post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021 https://doi.org/10.48550/arXiv.2104.05560 doi:10.48550/arXiv.2104.05560 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021 https://doi.org/10.1038/s41586-021-03426-1 doi:10.1038/s41586-021-03426-1 33723411 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021 https://doi.org/10.1101/2021.02.24.21251989 doi:10.1101/2021.02.24.21251989 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." Couzens 2021 https://doi.org/10.1101/2021.04.02.21254832 doi:10.1101/2021.04.02.21254832 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change. Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021 https://doi.org/10.1101/2021.02.24.21251989 doi:10.1101/2021.02.24.21251989 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." Couzens 2021 https://doi.org/10.1101/2021.04.02.21254832 doi:10.1101/2021.04.02.21254832 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change. Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively. Roquebert 2021 https://doi.org/10.1101/2021.03.19.21253971 doi:10.1101/2021.03.19.21253971 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." Couzens 2021 https://doi.org/10.1101/2021.04.02.21254832 doi:10.1101/2021.04.02.21254832 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change. Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036). Song 2021 https://doi.org/10.1101/2021.05.04.21256655 doi:10.1101/2021.05.04.21256655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio 341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). Frampton 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021 https://doi.org/10.1038/s41586-021-03426-1 doi:10.1038/s41586-021-03426-1 33723411 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021 https://doi.org/10.48550/arXiv.2104.05560 doi:10.48550/arXiv.2104.05560 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio 341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). Frampton 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49) Buchan 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking VSV pseudotype B.1.1.7 showed no significant difference in cell entry relative to wild type in 6 cell lines. Cell fusion proficiency was unchanged. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49) Buchan 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants. Lindstrøm 2021 https://doi.org/10.1101/2021.03.29.21254122 doi:10.1101/2021.03.29.21254122 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks. Munitz 2021 https://doi.org/10.1016/j.xcrm.2021.100264 doi:10.1016/j.xcrm.2021.100264 33899031 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Based on 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020, Rt of B.1.1.7 was 1.35x (95% CI 1.02-1.69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Graham 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks. Munitz 2021 https://doi.org/10.1016/j.xcrm.2021.100264 doi:10.1016/j.xcrm.2021.100264 33899031 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49) Buchan 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants. Lindstrøm 2021 https://doi.org/10.1101/2021.03.29.21254122 doi:10.1101/2021.03.29.21254122 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49) Buchan 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants. Lindstrøm 2021 https://doi.org/10.1101/2021.03.29.21254122 doi:10.1101/2021.03.29.21254122 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, but to a smaller extent than N501Y and the deletion alone. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Slight neutralization improvement on average in 16 health workers' convalescent sera. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding These key B.1.1.7 mutations as a combination neutralized slightly less well than D614G and this was noticeable in the lack of sera with high neutralizing titer for the viruses across 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,21762,21763,21764,21765,21766,21766,23399,23401,23402,23403,22915,22916,22917 H69del,H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 17.2x-fold lower (95% CI: 0.6x-0.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,21762,21763,21764,21765,21766,21766,23399,23401,23402,23403,22915,22916,22917 H69del,H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 13.0-fold lower (95% CI: 4.2x-4.6x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,22810,22811,22812,22813,22813,23009,23010,23012,23013 H69del,H69del,H69del,H69del,H69del,H69del,H69del,K417N,K417N,K417N,K417N,K417N,E484A,E484A,E484A,E484A NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Ontario, using a retrospective matched case (age, gender and onset date) study of 6,312 Omicron cases vs 8,875 Delta, the adjusted risk of hospitalization or death was 54% lower (HR=0.46, 95%CI: 0.27, 0.77) among Omicron cases, after adjusting for vaccination statis and time since 2nd shot. The ratio for >60yo was 0.55 (95%CI: 0.28-1.06), and <60yo was 0.30 (95%CI: 0.16-0.57). Ulloa 2021 https://doi.org/10.1101/2021.12.24.21268382 doi:10.1101/2021.12.24.21268382 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,23009,23010,23012,23013 H69del,H69del,H69del,H69del,H69del,H69del,H69del,E484A,E484A,E484A,E484A NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection, evidenced by a reinfection hazard ratio of 2.39 (CI95: 1.88-3.11) relative to primary infection in the initial part of South Africa's 4th covid-19 wave (November 2021). In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. [minimal variant signature for Omicron (B.1.1.529) used based on H69del PCR dropout observed in November 2021 coincident with the rise of Omicron] Pulliam 2021 https://doi.org/10.1101/2021.11.11.21266068 doi:10.1101/2021.11.11.21266068 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800 D80N NC_045512.2:g.238G>A YP_009724390.1:p.Asp80Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800 D80Y NC_045512.2:g.238G>T YP_009724390.1:p.Asp80Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This AA substitution outside the receptor binding domain in pseudotyped VSV promoted a 7.2% transduction rate in golden hamster cells, which was higher than that of human epithelial-like Huh-7 cells (6.6%). Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800,22188,22206,22597,22599,23012,23521,23522,23524,23525,23604 D80Y,I210del,D215G,R346K,R346K,E484K,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.238G>T,NC_045512.2:g.629_631del,NC_045512.2:g.644A>G,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp80Tyr,YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against A.VOI.V2 (first identified in Angola) reduced 8.0x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated that there is no free energy change (ddG) for this variant (i.e. same stability as wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion One individual of 30 in the study, with HLA supertype HLA*A24:02, had a linear epitope that overlaps this variant of concern. Redd 2021 https://doi.org/10.1101/2021.02.11.21251585 doi:10.1101/2021.02.11.21251585 33594378 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abolishes neutralizing activity of N-terminal-domain-directed mAb 4-19. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.351 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 71%, Day 209 54%. Detectable antibodies against B.1.351 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 79%, Day 209 58%. Detectable antibodies against B.1.351 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 63%, Day 43 100%, Day 119 71%, Day 209 79%. Decreased neutralization on some assays was seen especially in those vaccinees tested that were 71+. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In an Ontario long term care facility, cumulatively, weaker BNT162b2 vaccine stimulation, age/comorbidities, produced a ∼130-fold reduction in apparent neutralization titers in mean 88yo LTCH residents against Beta (B.1.351), relative to staff vaccinees against D614G wild type. 37.9% of 116 two-dose-mRNA-vaccinated residents had undetectable neutralizing antibodies to B.1.351. mRNA-1273 vaccinee sera displayed ~2 better neutralization than BNT162b2. [common defining B.1.351 mutations noted, as the manuscript does not provide details] Abe 2021 https://doi.org/10.1101/2021.08.06.21261721 doi:10.1101/2021.08.06.21261721 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, 7 of 15 neutralized this B.1.351 pseudotype that includes the L242del, and only one had titers above 100. Only one of the 15 sera achieved 80% neutralization. [compare to 5 and 1 for pseudotype without the deletion] Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~10-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~3 fold without the deletion] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were significant, but ~500x weaker than in previously infected patients after first dose. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v3 reduced 8.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Beta (B.1.351) variant is 0.4x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A two-dose regimen of (AstraZeneca) ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, vaccine efficacy against severe Covid-19 is undetermined. Madhi 2021 https://doi.org/10.1101/2021.02.10.21251247 doi:10.1101/2021.02.10.21251247 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 33972942 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 33972942 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination. Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Unlike wild type or B.1.1.7, B.1.351 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. PG: The virus used in these expriments has a non-typical deletion+sub in the 242 region. Montagutelli 2021 https://doi.org/10.1101/2021.03.18.436013 doi:10.1101/2021.03.18.436013 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Beta (B.1.351) has an IC50 fold change of 0.13x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Beta (B.1.351) has an IC50 fold change of 0.15x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001). Zhou 2021 http://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001). Zhou 2021 http://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~6x cleavage of S2 relative to WA1 (D614G) wildtype by Beta variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but A701V is downstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Beta Molnupiravir (MK-4482) had ~1.75x fold drop. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.351 v1 virus has reduced neutralization activity vs wild type: 34.5x (30 sera Pfizer median 9 days post 2nd dose) and 27.7x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Beta (B.1.351) has an IC50 fold change of 0.13x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001). Zhou 2021 http://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination. Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Compared to Alpha (B.1.1.7) variant, odds of progressing to severe disease were 1.24-fold (95% CI: 1.11-1.39) higher for Beta. Odds of progressing to critical disease were 1.49-fold (95% CI: 1.13-1.97) higher. Odds of COVID-19 death were 1.57-fold (95% CI: 1.03-2.43) higher. Abu-Raddad 2021 https://doi.org/10.1101/2021.08.02.21261465 doi:10.1101/2021.08.02.21261465 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 34 convalescent cases 4–9 weeks following infection in June 2020, before the emergence of B.1.1.7, neutralization titers against B.1.351 were, on average, 13.3-fold reduced compared with an early Victoria sample (p < 0.0001). Significantly, 18 of 34 samples failed to reach 50% neutralization at a plasma dilution of 1:20, with a number showing a near total reduction of neutralization activity. In 13 convalescent cases 4–9 weeks following infection with B.1.1.7, neutralization titers against B.1.351 were, on average, 3.1-fold reduced compared with an early Victoria sample (p < 0.0001). Zhou 2021 https://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Testing against B.1.351 the 20 most effective mAbs (19 anti-RBD, 1 anti-NTD) from a screen of 377 against wild type, 4 of 20 antibodies had >10-fold fall in neutralization titers, with most of these showing a complete knockout of activity. This is in line with the key roles of K417, E484, and N501, in particular E484, in antibody recognition of the ACE2 interaction surface of the RBD. Regeneron mAb cocktail: The neutralization of REGN10987 was unaffected by B.1.351, while REGN10933 was severely impaired (773-fold). AstraZeneca mAb cocktail: Neutralization by the AZ pair of antibodies was little affected on B.1.351 compared with Victoria. Zhou 2021 https://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.351 defining mutations: Significant shift to infection in those without pre-existing conditions (79.6% vs 89% for non-VOC cases). Significant increase in hospitalization rate (19.3% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.3% vs 0.6% for non-VOC cases). PG: seems to be different notations around the LAL deletion, using the minimal shared definition to catch as many as possible. Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The B.1.351 variant constellation causes an ∼20-fold increase in affinity for ACE2 compared with Wuhan RBD, which may influence transmissibility. Zhou 2021 https://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccine plasma neutralization of B.1.351-spike virus was nominally robust but lower (~3x) than other variants of concern. Liu 2021 https://doi.org/10.1056/NEJMc2102017 doi:10.1056/NEJMc2102017 33684280 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) humoral response durability In a prospective study of 107 hospitalized patients, decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7 and P.1 variants for at least 6 months (last of two samples taken) in patients previously hospitalized for COVID-19. A weaker protection was however observed for the B.1.351 variant. Betton 2020 https://doi.org/10.1093/cid/ciab308 doi:10.1093/cid/ciab308 33851216 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Beta (B.1.351) has an IC50 fold change of 0.88x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using B.1.351 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~3-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~10 fold with L242del] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were signficiant, but >100x weaker than in previously infected patients after first dose. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, one third (5/15) of sera neutralized this B.1.351 pseudotype and only three had ID50 titers above 100. Only two of the 15 sera achieved 80% neutralization. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission. Yinda 2021 https://doi.org/10.1101/2021.05.05.442780 doi:10.1101/2021.05.05.442780 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence Inoculation with the B.1.351 isolate resulted in lower clinical scores in 6 rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. Our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity. Munster 2021 https://doi.org/10.1101/2021.05.07.443115 doi:10.1101/2021.05.07.443115 34382034 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 4 health care workers in the 20's and 30's with no underlying conditions and seropositivity or confirmed 2020 SARS-CoV-2 infections were confirmed to have B.1.351 infection during a Februrary 2021 hospital outbreak in Luxembourg. Symptoms were mostly mild on first infection, and milder on second infection. Staub 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.18.2100423 doi:10.2807/1560-7917.ES.2021.26.18.2100423 33960291 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission. Yinda 2021 https://doi.org/10.1101/2021.05.05.442780 doi:10.1101/2021.05.05.442780 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351. 2021 https://www.fda.gov/media/146217/download False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer Solfrosi 2021 https://doi.org/10.1084/jem.20202756 doi:10.1084/jem.20202756 33909009 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.351 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the B.1.351 variants used, using the most popular as a stad in] McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In a Syrian hamster model, B.1.351 variant virus had >4x reduction in YRNT90 (measure of neutralization) using wild type convalescent sera. PG: Note that exact sequence for B.1.351 used was not disclosed. Cochin 2021 https://doi.org/10.1101/2021.04.19.440435 doi:10.1101/2021.04.19.440435 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy During an outbreak of SARS-CoV-2 501Y.V2 in a nursing home, all non-vaccinated residents (5/5) versus half of those fully vaccinated 2-5 weeks prior with BNT162b2 (13/26) were infected. Two of 13 vaccinated versus 4 of 5 non-vaccinated residents presented severe disease. BNT162b2 did not prevent the outbreak, but reduced transmission and disease severity. Among the 13 fully vaccinated residents who were infected, 2 (15.4%) presented with an asymptomatic disease, 9 (69.2%) developed mild to moderate symptoms, and 2 (15.4%) progressed to severe disease with fatal evolution secondary to acute respiratory distress syndrome (ARDS). There was no relationship between anti-S antibody levels at diagnosis and disease severity. Overall, the proportion of residents with severe disease in the non-vaccinated group (4/5) was higher than that in the vaccinated group (2/13). Only 1 vaccinated staff, but 10 unvaccinated were infected in the outbreak (no severe disease). Bailly 2021 https://doi.org/10.1093/cid/ciab446 doi:10.1093/cid/ciab446 33993228 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer Solfrosi 2021 https://doi.org/10.1084/jem.20202756 doi:10.1084/jem.20202756 33909009 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.351 v3 virus has reduced neutralization activity vs wild type: 42.4x (30 sera Pfizer median 9 days post 2nd dose) and 19.2x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351. 2021 https://www.fda.gov/media/146217/download False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351. 2021 https://www.fda.gov/media/146217/download False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.351 in 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.351 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0020 for moderate resistance. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.351 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. B.1.1.351 variant constellation ablates Class 3 N-terminal domain targeting antibodies COV2-2489 and COV2-2676 (the only two tested). Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H] Supasa 2021 https://doi.org/10.1016/j.cell.2021.02.033 doi:10.1016/j.cell.2021.02.033 33743891 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccine elicited antibodies neutralized virus with the B.1.351 spike protein had an average 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness VSV pseudotype B.1.351 entry mediated by the S proteins of the B.1.351 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.351 lineage effectiveness was observed as 16.9% (95% CI [10.4,23.0]) against infection, and 0% against severe/critical/fatal disease (95% CI [0-19.0]). Two weeks or more after 2nd dose, effectiveness climbed to 75.0% [70.5,78.9] against infection, and 100% against severe/critical/fatal disease (95% CI [73.7,100]). Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.351 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding VSV pseudotype B.1.351 showed 7.86-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections). Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking VSV pseudotype B.1.351 showed slight decrease in cell entry relative to wild type in 263T-ACE2 (kidney) cell line, and slight increase in Calu-3 (lung). Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abrogates Bamlanivimab, Etesevimab, or their combined use neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Approximately 6-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In one of eight cell lines tested (293T lung cells), a modest increase in cell entry was observed. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H] Supasa 2021 https://doi.org/10.1016/j.cell.2021.02.033 doi:10.1016/j.cell.2021.02.033 33743891 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846 T95I NC_045512.2:g.284C>T YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 65yo female with no severe Covid-19 risk factors tested positive 36 days after second dose of BNT162b2 (Pfizer) vaccine. Presented with fatigue, sinus congestion, and a headache developed; her symptoms plateaued and began to resolve six days later. [Mising genome coverage in regions of Spike covering clinically relevant mutations K417T, L452R, E484K, A701V, D796H, N501Y] Hacisuleyman 2021 https://doi.org/10.1056/NEJMoa2105000 doi:10.1056/NEJMoa2105000 33882219 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22317,22319,22320,23399,23401,23402,23403 T95I,D253G,D253G,D253G,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio B.1.526 (Iota) substantially increased IFR in older adults: by 46% (95% CI: 7.4 – 84%) among 45-64 year-olds, 82% (95% CI: 20 – 140%) among 65-74 year-olds, and 62% (95% CI: 45 – 80%) among 75+ during Nov 2020 – Apr 2021, compared to baseline IFR estimated for preexisting variants. [minimum clade defining mutations listed] Yang 2021 https://doi.org/10.1101/2021.08.04.21261596 doi:10.1101/2021.08.04.21261596 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against B.1.621. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera from vaccinees [ChAdOx1 and BNT162b2 primarily used in UK] shows decreased ability to neutralize B.1.621 compared to first wave virus and Alpha, with a magnitude of change similar to Beta. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 69 test-positive were Mu. Two dose vaccine efficacy against Mu was 90.4% (73.9-96.5%), one dose VE was 45.8% (0.0-88.9%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Sera from individuals who have been infected with Delta does not have strong neutralising activity against B.1.621 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 12.4x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. [This is a greater reduction than Beta @ 8.2x] Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Using live B.1.621 virus and a cytopathic effect-based assay, sera from 37 Pfizer/BioNTech BNT162b2 vaccinees collected 10-20 days post-booster showed significantly lower (95) but still ""robust"" neutralization than against ancestral B.1 virus (107)." Messali 2021 https://doi.org/10.1002/jmv.27247 doi:10.1002/jmv.27247 34329486 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 7.6x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. [This is a greater reduction than Beta @ 6.3x] Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403 T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 4.4-fold lower (95% CI: 4.3x-4.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403 T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 1.5x-fold lower (95% CI: 0.05x-0.07x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,23012,23271,23399,23401,23402,23403,23604,23948 T95I,E484K,A570D,D614G,D614G,D614G,D614G,P681H,D796H NC_045512.2:g.284C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2386G>C YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp796His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 51yo female with no severe COVID-19 risk factors tested positive 19 days after second dose of mRNA-1273 (Moderna) vaccine. Presented with sore throat, congestion, and headache developed; the next day she lost her sense of smell. Symptoms resolved over a one week period. Serum obtained 4 days after symptom onset was tested for neutralization against wild-type virus, the E484K mutant, and the B.1.526 variant. It was equally effective against each. These data suggest that the antibody response recognized these variants but was nonetheless insufficient to prevent a breakthrough infection. The virus detected matched neither B.1.1.7 nor B.1.526 VOC strains in wide circulation in New York at the time of infection, though shared some mutations. Hacisuleyman 2021 https://doi.org/10.1056/NEJMoa2105000 doi:10.1056/NEJMoa2105000 33882219 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,23399,23401,23402,23403 T95I,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21855 S98F NC_045512.2:g.293C>T YP_009724390.1:p.Ser98Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly enhanced the transduction rate in raccoon dog (Nyctereutes procyonoides) kidney (62.4%) and Rickett’s big-footed bat (Myotis pilosus) kidney (45.0%) cell cultures compared to epithelial-like human Huh-7 cells (38.9%). Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21929 A123S NC_045512.2:g.367G>T YP_009724390.1:p.Ala123Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected in passage with mAb COV2-2489 during alanine mutagenesis antibody mapping experiment. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 33501445 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21969 C136Y NC_045512.2:g.407G>A YP_009724390.1:p.Cys136Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massively decreases N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21969 C136Y NC_045512.2:g.407G>A YP_009724390.1:p.Cys136Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected twice in passage with mAb COV2-2489. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 33501445 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. [PG: This mutation is adjacent to a well known deletion, which may confound the significance of this variant] Lucaci 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events These variants dominate in mink infections in North America, sometime supplemented with F486L. The Y453F variant found in other jurisdictions in mink infections is notably absent in North America. 2021 https://doi.org/10.1101/2021.03.18.21253734v3 doi:10.1101/2021.03.18.21253734v3 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Relative to B.1, Kappa (B.1.617.1) shows 5.71x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Average 2x neutralization efficiency decrease against sera from 26 Phase II trial Covaxin (BBV152) vaccine recipents. Very similar to B.1.1.7 (~2x) in the same study, and the neutralization from 17 sera of natural infections across B1 lineages. Yadav 2021 https://doi.org/10.1101/2021.04.23.441101 doi:10.1101/2021.04.23.441101 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.1) showed a 1.12x increase in binding (KD) relative to D614G, but described as ""not significant"". [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cluster of B.1.617[.1] infections related to travel from India to USA, one patient with mild symptoms had received their second dose of Pfizer vaccine more than two weeks before the infection [i.e. vaccine breakthrough]. Verghese 2021 https://doi.org/10.1128/JCM.00741-21 doi:10.1128/JCM.00741-21 33952596 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.617.1) showed a 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.617.1) showed a 1.79x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~3.5x cleavage of S2 relative to WA1 (D614G) wildtype by Kappa (B.1.617.1) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~4.5x for closely related Delta B.1.617.2 also with P681R at the cleavage site). Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1, Kappa (B.1.617.1) shows mean 1.97x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Kappa (B.1.617.1) has an IC50 fold change of 2.3x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Kappa (B.1.617.1) has an IC50 fold change of 0.13x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Kappa (B.1.617.1) has an IC50 fold change of 80.2x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Kappa (B.1.617.1) has an IC50 fold change of 0.68x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.2 has an IC50 fold change of 0.04x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Omicron BA.2 has an IC50 fold change of 0.09x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.2 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Omicron BA.2 has an IC50 fold change of 0.08x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.2 has an IC50 fold change of 0.07x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Omicron BA.2 variant is 0.8x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.2 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21974 D138Y NC_045512.2:g.412G>T YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.43 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21977 P139S NC_045512.2:g.415C>T YP_009724390.1:p.Pro139Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2:g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2:g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected once in passage with mAb COV2-2676. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 33501445 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2:g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2:g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990 Y145del,Y145del NC_045512.2:g.432_434del,NC_045512.2:g.432_434del YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990 Y145del,Y145del NC_045512.2:g.432_434del,NC_045512.2:g.432_434del YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient. McCarthy 2021 https://doi.org/10.1126/science.abf6950 doi:10.1126/science.abf6950 33536258 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990,21993,21995,23012,23399,23401,23402,23403 Y145del,Y145del,H146del,H146del,E484K,D614G,D614G,D614G,D614G NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.436_438del,NC_045512.2:g.436_438del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.His146del,YP_009724390.1:p.His146del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Normalized for particle number, on ACE2.293T cells showed that the B.1.618 spike protein was about as infective as D614G wild type. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21993,21995 H146del,H146del NC_045512.2:g.436_438del,NC_045512.2:g.436_438del YP_009724390.1:p.His146del,YP_009724390.1:p.His146del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient. McCarthy 2021 https://doi.org/10.1126/science.abf6950 doi:10.1126/science.abf6950 33536258 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21997,21998,21999,22000,22001 K147E,K147E,K147E,K147E,K147E NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21997,21998,21999,22000,22001 K147E,K147E,K147E,K147E,K147E NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2X28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21998 H146Y NC_045512.2:g.436C>T YP_009724390.1:p.His146Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Massive reduction in 4A8 monoclonal antibody EC50 (i.e. ablated recognition), but much milder effect on mAbs within antigenic supersite ""i""" McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22001 K147Q NC_045512.2:g.439A>C YP_009724390.1:p.Lys147Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22002 K147T NC_045512.2:g.440A>C YP_009724390.1:p.Lys147Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22002 K147T NC_045512.2:g.440A>C YP_009724390.1:p.Lys147Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massively decreases N terminal domain antigen recognition by supersite i mAbs S2M28, S2X28, S2X333, 4A8 (but not S2L28). McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22003 K147N NC_045512.2:g.441A>T YP_009724390.1:p.Lys147Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22005 N148S NC_045512.2:g.443A>G YP_009724390.1:p.Asn148Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong positive selection (up to 72% of supernatant sequences) under six rounds of COV47 convalescent plasma passage Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22010 K150E NC_045512.2:g.448A>G YP_009724390.1:p.Lys150Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong positive selection (up to 40% of supernatant sequences) under three rounds of COV47 convalescent plasma passage Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22010 K150E NC_045512.2:g.448A>G YP_009724390.1:p.Lys150Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22011 K150T NC_045512.2:g.449A>C YP_009724390.1:p.Lys150Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 22% of supernatant sequences) after COV47 convalescent plasma assay Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22011 K150R NC_045512.2:g.449A>G YP_009724390.1:p.Lys150Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 18% of supernatant sequences) under two rounds of COV47 convalescent plasma passage Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22016,22016 W152R,W152R NC_045512.2:g.454T>A,NC_045512.2:g.454T>C YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For NTD-binding neutralizing antibody ADI-56479 this mutation causes a 1000x drop in neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22016,22016 W152R,W152R NC_045512.2:g.454T>A,NC_045512.2:g.454T>C YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22018 W152C NC_045512.2:g.456G>T YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Pseudoviruses carrying the W152C mutation demonstrated small increases in cell entry compared to D614G alone in 293T cells and human airway organoids. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22018 W152C NC_045512.2:g.456G>T YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The W152C mutation reduced recognition of six NTD neutralizing mAbs, including a complete loss of binding for two of them, with a complementary pattern to that observed for S13I (also found in lineage B.1.427/B.1.429) out of 11 neutralizing mAbs evaluated. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022 E154K NC_045512.2:g.460G>A YP_009724390.1:p.Glu154Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022,22915,22916,22917,23012,23399,23401,23402,23403,23604 E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Approximately 2-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022,22915,22916,22917,23012,23399,23401,23402,23403,23604 E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abrogates Bamlanivimab neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Significant decrease in combined Etesevimab+Bamlanivimab neutralization except at the highest concentration measured. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022,22915,22916,22917,23012,23399,23401,23402,23403,23604 E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In two of eight cell lines tested (Caco-2 intenstinal and Calu-3 lung), a modest increase in cell entry was observed. This increase was not observed in a Calu-3 cell line with overexpressed ACE2. [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022,22915,22916,22917,23012,23399,23401,23402,23403,23604 E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 15 Pfizer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~3x (compared to ~11x for B.1.351). [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034 R158G,R158G NC_045512.2:g.467_472del,NC_045512.2:g.472A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22033,23012,23604 F157L,E484K,P681R NC_045512.2:g.471C>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against A.23.1-v2 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22033,23604 F157L,P681R NC_045512.2:g.471C>A,NC_045512.2:g.2042C>G YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against A.23.1-v1 reduced 1.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22036 R158S NC_045512.2:g.474A>T YP_009724390.1:p.Arg158Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected three times in passage with mAb COV2-2489. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 33501445 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:03. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type C*07:02. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DPB1*04:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:02. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:02. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*16:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*07:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22107,22111 Q183H,Q183H NC_045512.2:g.549G>T,NC_045512.2:g.549G>T YP_009724390.1:p.Gln183His,YP_009724390.1:p.Gln183His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 33176080 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22132 R190S NC_045512.2:g.570G>T YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.69 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604 R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in B.1.640.2 variant was ~1000x folds more significant in 8 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604 R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1.640.2 variant was ~5.6x folds more significant in 9 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22188,23399,23401,23402,23403 I210del,D614G,D614G,D614G,D614G NC_045512.2:g.629_631del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection A 42yo Iranian male was reinfected with B.1.36 lineage virus 128 days after infection with genetically distinct B.1.36 virus, with negative PCR tests in between. In the first instance patient presented with cough, headache, severe diarrhea. In the second instance symptoms were more severe: body pain, shortness of breath, headache and anosmia. Anti-SARS-CoV-2 IgG and IgM tests were negative after both episodes. [Non-seroconversion may be associated with elevated risk of re-infection] [I210del is a homoplasy that has appeared in several disparate parts of the global phylogenetic tree, including A and B lineages, primarily in LMICs] Salehi-Vaziri 2021 https://doi.org/10.1016/j.virusres.2021.198421 doi:10.1016/j.virusres.2021.198421 33836204 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:01. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*13:02. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:02. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.98 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22224,22227 A222V,A222V NC_045512.2:g.665C>T,NC_045512.2:g.665C>T YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22224,22227,23399,23401,23402,23403 A222V,A222V,D614G,D614G,D614G,D614G NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) humoral response durability 27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3), i.e. with a 9 month interval. Both cases were mild. No significant differences in the neutralizing capacity of the two lineages were observed in 4 sera taken (1 pre-reinfection, three post-reinfection). Neutralizing antibody titres (IC50) before and immediately after re-infection were <300 against both strains, and jumped >7x upon re-infection. Viral titres were also higher in the second case. Second case also includes N:p.A220V Brehm 2021 https://doi.org/10.3390/v13040661 doi:10.3390/v13040661 33921216 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22224,22227,23399,23401,23402,23403 A222V,A222V,D614G,D614G,D614G,D614G NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3). Both cases were mild. Second case also includes N:p.A220V Brehm 2021 https://doi.org/10.3390/v13040661 doi:10.3390/v13040661 33921216 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22293 L244S NC_045512.2:g.731T>C YP_009724390.1:p.Leu244Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22301 S247R NC_045512.2:g.739A>C YP_009724390.1:p.Ser247Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22304 Y248H NC_045512.2:g.742T>C YP_009724390.1:p.Tyr248His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22314 P251L NC_045512.2:g.752C>T YP_009724390.1:p.Pro251Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317 G252D NC_045512.2:g.755G>A YP_009724390.1:p.Gly252Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317,22319,22320 D253G,D253G,D253G NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317,22319,22320 D253G,D253G,D253G NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22319 D253Y NC_045512.2:g.757G>T YP_009724390.1:p.Asp253Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22323 S254Y NC_045512.2:g.761C>A YP_009724390.1:p.Ser254Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22323 S254F NC_045512.2:g.761C>T YP_009724390.1:p.Ser254Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22326 S255F NC_045512.2:g.764C>T YP_009724390.1:p.Ser255Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22328,22329,22331 G257S,G257S,G257S NC_045512.2:g.769G>A,NC_045512.2:g.769G>A,NC_045512.2:g.769G>A YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334 W258R NC_045512.2:g.772T>C YP_009724390.1:p.Trp258Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334 W258R NC_045512.2:g.772T>C YP_009724390.1:p.Trp258Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334,22879,22881,22882,22882,22904,22910,23012 W258R,N440K,N440K,N440K,N440K,N450D,N450D,E484K NC_045512.2:g.772T>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22340 A260T NC_045512.2:g.778G>A YP_009724390.1:p.Ala260Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22344 G261D NC_045512.2:g.782G>A YP_009724390.1:p.Gly261Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Multiple mink but no humans on one farm in Denmark, potential adaptation. Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 33172935 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22377 P272L NC_045512.2:g.815C>T YP_009724390.1:p.Pro272Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*02:01. Dolton 2021 https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf doi:10.1101/2021.06.21.21259010v2.full.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22377 P272L NC_045512.2:g.815C>T YP_009724390.1:p.Pro272Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*08:01. Dolton 2021 https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf doi:10.1101/2021.06.21.21259010v2.full.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 1.2x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.3 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22583 V341I NC_045512.2:g.1021G>A YP_009724390.1:p.Val341Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22595,22596,22597,22599 R346T,R346T,R346T,R346T NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22595,22596,22597,22599 R346T,R346T,R346T,R346T NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.15 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22595,22596,22597,22599,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22939,22942,22942,22992,23009,23010,23012,23013,23027,23029,23030,23031,23053,23054,23055,22992,22995,23060,23061,23062,23063,23071,23074,23075 R346T,R346T,R346T,R346T,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N460K,N460K,N460K,S477N,E484A,E484A,E484A,E484A,F490S,F490S,F490S,F490S,Q498R,Q498R,Q498R,T478K,T478K,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The hACE2-binding affinity of XBB.1.5 RBD has a dissociation constant KD of 3.4 nM, where S486P is the distinguishing Spike mutation vs parent XBB.1 RBD with a much weaker KD (19 nM), as measured by surface plasmon resonance (SPR) assays. Yue 2023 https://doi.org/10.1101/2023.01.03.522427 doi:10.1101/2023.01.03.522427 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346K,R346K NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346I,R346I NC_045512.2:g.1037G>T,NC_045512.2:g.1037G>T YP_009724390.1:p.Arg346Ile,YP_009724390.1:p.Arg346Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Provides ~80% escape from mAb COV2-2130, even though its appearance in culture is formed without selective mAb pressure. Dong 2021 https://doi.org/10.1101/2021.01.27.428529 doi:10.1101/2021.01.27.428529 33532768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346K,R346K NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation, which has emerged in some Omicron sequences, has a 0.7x reduction in neutralization activity with Sotrovimab in a VSV model on Vero E6 cells. [Omicron sequences with R346K may very well have a non-additive neutralization rather than 2.7x+0.7x = 3.4x] Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346K,R346K NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 53% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 2/3 antibody C603. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 2/3 antibody C603. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Positive selection (up to 30% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22622 N354D NC_045512.2:g.1060A>G YP_009724390.1:p.Asn354Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.13 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22624 N354K NC_045512.2:g.1062C>A YP_009724390.1:p.Asn354Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22627,22629 K356T,K356T NC_045512.2:g.1067A>C,NC_045512.2:g.1067A>C YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.14 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22629 K356R NC_045512.2:g.1067A>G YP_009724390.1:p.Lys356Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22632 R357K NC_045512.2:g.1070G>A YP_009724390.1:p.Arg357Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.18 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2:g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as ""stabilizing"" since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2:g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.72 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2:g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as ""stabilizing"" since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2:g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22661 V367I NC_045512.2:g.1099G>A YP_009724390.1:p.Val367Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22679 S373P NC_045512.2:g.1117T>C YP_009724390.1:p.Ser373Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Reduce affinity for mildly cross-reactive CR3022 (2003 pandemic SARS monoclonal antibody cross-reactive to SARS-CoV-2) Long 2020 https://doi.org/10.1128/mBio.02707-20 doi:10.1128/mBio.02707-20 33127862 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22679,23009,23010,23012,23013 S373P,E484A,E484A,E484A,E484A NC_045512.2:g.1117T>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility On December 7, 2021 the estimate of Omicron effective reproduction rate (Rt) is 3.12 [presumably R0 is higher], compared to 1.12 for the dominant Delta VOC at that time. [shorthand of variant list shraed by all contemporary BA lineage used here] 2021 https://doi.org/10.47326/ocsat.dashboard.2021.1.0 doi:10.47326/ocsat.dashboard.2021.1.0 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22686 S375F NC_045512.2:g.1124C>T YP_009724390.1:p.Ser375Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. Lucaci 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22696 K378N NC_045512.2:g.1134G>T YP_009724390.1:p.Lys378Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for mildly neutralizing COV2-2677 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23402,23403 P384L,D614G,D614G,D614G,D614G NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23402,23403 P384L,D614G,D614G,D614G,D614G NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23402,23403 P384L,D614G,D614G,D614G,D614G NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22745 V395I NC_045512.2:g.1183G>A YP_009724390.1:p.Val395Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22766 I402V NC_045512.2:g.1204A>G YP_009724390.1:p.Ile402Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22783,22784,22785,22786,22786 R408S,R408S,R408S,R408S,R408S NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22783,22784,22785,22786,22786,23009,23010,23012,23013,23060,23061,23062,23063 R408S,R408S,R408S,R408S,R408S,E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a study of 481 vaccinees going from lowest to highest infection rate, 2 doses of CoronaVac and 1 dose of BNT162b2 had the lowest infection rate at 6.3%, then it was 3 doses of BNT162b2 having a infection rate of 16.6%. 2 and 3 doses of CoronaVac had 48.6% and 20.6% infection rate respectively. 2 doses of BNT162b2 has the highest infection rate at 49.2%. Zhou 2022 https://doi.org/10.1101/2022.05.09.491254 doi:10.1101/2022.05.09.491254 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotyped virus model ablates binding by RBD-directed mAbs CB6 and 910-30 (targeting the inner side of the RBD). Pseudotyped virus model impairs binding by RBD-directed mAbs 4-20 and REGN10933. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 1.1 fold drop in IC50 of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The K417N mutation decreased the affinity ~4 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs) Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs) Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C682, and to a lesser extent C614 and C660 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects >20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against IgG1 monoclonal antibody ab1. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.86 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~6x binding against this isolated mutation. Estesevimab lost ~100x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 7.5 fold decrease in KD value for antibody binding of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 1.5 fold decrease in KD value of antibody binding of ACE2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 3-fold decrease in affinity compared to wild-type RBD on the cell surface (Kd = 145.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 19 convalescent human sera ~1mo post infection, Two-tailed Wilcoxon matched-pairs signed-rank test shows mild resistance P=0.0361. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 36.9 fold decrease in KD value for antibody binding of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape "27% of 44 early pandemic exposure convalescent plasma/sera lose all activity against a RBD triple mutant pseudovirus (RBD mutatants of the 501Y.V2 ""South African"" lineage), while only 23% retained high titres" Wibmer 2021 https://doi.org/10.1101/2021.01.18.427166 doi:10.1101/2021.01.18.427166 33501446 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" Wibmer 2021 https://doi.org/10.1101/2021.01.18.427166 doi:10.1101/2021.01.18.427166 33501446 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" Wibmer 2021 https://doi.org/10.1101/2021.01.18.427166 doi:10.1101/2021.01.18.427166 33501446 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of the B.1.351 RBD variants for ACE2 increased by 3.7 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 1.4-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.351 key variants lentivirus. Compare to 8.8-fold reduction against cultured B.1.351 virus. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM). Ramanathan 2021 https://doi.org/10.1101/2021.02.22.432359 doi:10.1101/2021.02.22.432359 33655251 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y. Laffeber 2021 https://doi.org/10.1101/2021.02.22.432357 doi:10.1101/2021.02.22.432357 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021 https://doi.org/10.1101/2021.03.04.433887 doi:10.1101/2021.03.04.433887 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y. Laffeber 2021 https://doi.org/10.1101/2021.02.22.432357 doi:10.1101/2021.02.22.432357 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021 https://doi.org/10.1101/2021.03.04.433887 doi:10.1101/2021.03.04.433887 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021 https://doi.org/10.1101/2021.03.04.433887 doi:10.1101/2021.03.04.433887 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021 https://doi.org/10.1101/2021.03.04.433887 doi:10.1101/2021.03.04.433887 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM). Ramanathan 2021 https://doi.org/10.1101/2021.02.22.432359 doi:10.1101/2021.02.22.432359 33655251 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from B.1.351. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y. Laffeber 2021 https://doi.org/10.1101/2021.02.22.432357 doi:10.1101/2021.02.22.432357 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load B.1.351 and P.1 samples showed average Ct cycle threshold of 22.2 vs 23 for wildtype (i.e. ~60% higher viral load) comparing 3360 and 22535 samples respectively. Roquebert 2021 https://doi.org/10.1101/2021.03.19.21253971 doi:10.1101/2021.03.19.21253971 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibodies ab8 and IgG1 ab1. Complete loss for the same antibodies was also observed against S1 pseudotyped and full Spike protein trimers with both B.1.351 and P.1 lineage variants, with slight binding signal for P.1 against IgG1 at the highest concentration tested (1uM). Complete loss of neutralization by these two antibodies was also observed. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This combination showed ~3x increase binding to ACE2 vs wild type, about half that of the B.1.1.7 lineage, suggesting that the K417N mutation is slightly detrimental to ACE2 binding, probably as a result of disrupting the salt bridge formed with ACE2 residue D30 Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In Moderna vaccinee sera, 2.7x reduction in neutralization, and 6.4 for the full B.1.351 Spike mutation complement, but despite the observed decreases, titers in human vaccinee sera against the B.1.351 variant remained at clinically significant level of ~1/300. Wu 2021 https://doi.org/10.1101/2021.01.25.427948 doi:10.1101/2021.01.25.427948 33501442 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China). Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility 36,590 variant-specific RT-PCR tests were performed on samples collected between April 12 and May 7, 2021 in France to compare variant spread. Compared to January to March 2021, B.1.351 variant had a significant transmission advantage over B.1.1.7 in some regions (15.1 to 16.1% in Île-de-France and 16.1 to 18.8% in Hauts-de-France). This shift in transmission advantage is consistent with the immune evasion abilities of B.1.351 and the high levels of immunization in these regions. Roquebert 2021 https://doi.org/10.1101/2021.05.12.21257130 doi:10.1101/2021.05.12.21257130 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure. Pearson 2021 https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant of key B.1.351 lineage mutations showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China). Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure. Pearson 2021 https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Average ~10-fold reduction in neutralization efficacy in convalescent sera of 16 health workers infected in Spring 2020. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) with enrollment June 24 and November 9, 2020 from ~2000 HIV-negative 18-64 year olds (1:1 placebo to treatment), incidence of serious adverse events 14 or more days post- 2nd dose was balanced between the vaccine and placebo groups. A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed 3.5x reduction in neutralization (ID50) for B.1.351 RBD pseudotype HIB-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a similar 3.2x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera). Madhi 2021 https://doi.org/10.1056/NEJMoa2102214 doi:10.1056/NEJMoa2102214 33725432 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 2 (B.1.351) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2. Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abolished neutralization by mAbs CQ026 and CQ038, greatly diminished neutralization by CQ012 and CQ046. Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23041,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trachea viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~750x fold drop in the R3P1-E4 antibody in comparison to the IgG control. Li 2022 https://doi.org/10.1186/s13578-022-00794-7 doi:10.1186/s13578-022-00794-7 35581593 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23041,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Lung viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~2266x fold drop in the R3P1-E4 antibody in comparison to the IgG control. Li 2022 https://doi.org/10.1186/s13578-022-00794-7 doi:10.1186/s13578-022-00794-7 35581593 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23041,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness 100% of the 5 8‑month‑old male R3P1-E4 antibody treated mice suvived 14 days after infection while only 60% the control group mice survived 5 days post infection. Li 2022 https://doi.org/10.1186/s13578-022-00794-7 doi:10.1186/s13578-022-00794-7 35581593 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~5x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied] Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (no synergy as level approx. that of N501Y alone). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 57.1 fold decrease in KD value for antibody binding of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.64 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 1.1 fold decrease in KD value of antibody binding of ACE2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.25 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In vitro selection against class 1 antibody C682 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The K417T mutation decreased the affinity ~2 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~16x binding against this isolated mutation. Estesevimab lost ~16x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 2.9 fold decrease in KD value for antibody binding of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 2.6 fold increase in IC50 of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,23012,23060,23061,23062,23063 K417T,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from P.1. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,23012,23060,23061,23062,23063 K417T,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of the P.1 RBD variants for ACE2 increased by 5.3 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The KD for the pseudotyped P.1-ACE2 interaction is 4.8 nM, showing that binding to P.1 is essentially indistinguishable from B.1.351 (4.0 nM), which binds with ~19x greater affinity that wild type. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22851 T430I NC_045512.2:g.1289C>T YP_009724390.1:p.Thr430Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22865 A435S NC_045512.2:g.1303G>T YP_009724390.1:p.Ala435Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to neutralizing mAb H014 (on D614G background) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The N440K variant produced ten times higher infectious viral titers than a prevalent A2a strain, and over 1000 folds higher titers than a much less prevalent A3i strain prototype in Caco2 cells. Interestingly, A3i strain showed the highest viral RNA levels, but the lowest infectious titers in the culture supernatants, indicating the absence of correlation between the RNA content and the infectivity of the sample. Tandel 2021 https://doi.org/10.1101/2021.04.30.441434 doi:10.1101/2021.04.30.441434 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 0.7x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects N501Y substitution decreased the neutralizing and binding activities of CB6 and increased that of BD-23 Cheng 2021 https://doi.org/10.1186/s12985-021-01554-8 doi:10.1186/s12985-021-01554-8 33910569 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Positive selection (up to 45% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, eliminated in subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 3 antibody C669 mildly selected for the emergence of the N440K mutation in vitro (in contrast to N440H which caused mild escape in Class 1/2 mAb C653). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882,23399,23401,23402,23403 N440K,N440K,N440K,N440K,D614G,D614G,D614G,D614G NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection A 47yo Indian male was reinfected with B.1.36 lineage virus in September 2020 after infection with genetically distinct B.1.36 virus in July, with negative PCR tests in between. While the forst episode was asymptomatic, the second included fever, cough, and malaise. The second case additionally contained stopgain ORF3a:E261* Rani 2021 https://doi.org/10.1002/jmv.26997 doi:10.1002/jmv.26997 33818797 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444T NC_045512.2:g.1331A>C YP_009724390.1:p.Lys444Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444R NC_045512.2:g.1331A>G YP_009724390.1:p.Lys444Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Identified in 6/20 replicates of recombinant VSV growth in the presence of mAb COV2-2130. Dong 2021 https://doi.org/10.1101/2021.01.27.428529 doi:10.1101/2021.01.27.428529 33532768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444T NC_045512.2:g.1331A>C YP_009724390.1:p.Lys444Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Results in 3.7-fold drop in neutralization potency for COVA2-29, which is a cluster I RBD141 specific antibody. Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444R NC_045512.2:g.1331A>G YP_009724390.1:p.Lys444Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 20% of supernatant sequences) under two rounds of COV-NY convalescent plasma passage, eliminated in rounds three and four Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444T NC_045512.2:g.1331A>C YP_009724390.1:p.Lys444Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abolishes binding efficiency vs wild type for mAb REGN10933. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects ~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 14% of supernatant sequences) after COV-NY convalescent plasma assay Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Improvement in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-01 and moderately resistant to 2H04 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22896 V445A NC_045512.2:g.1334T>C YP_009724390.1:p.Val445Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 41% appearance in 2 passages against Regeneron monoclonal antibody RGN10987 @ 10ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2499 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 1 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed a ~4x drop in sensitivity. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-02, SARS2-32 and SARS2-35 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Decrease in neutralization capability of all 4 convalescent sera tested (1 ablated). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations), triple replicates. Against a broader panel of 16 convalescent plasma (no replicates), reductions in neutralization are considerably less dramatic in pattern, and sometime neutralization increases. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 95% appearance in 2 passages against Regeneron monoclonal antibody RGN10934 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 4 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Most effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-07 nd moderately resistant to SARS2-16 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910,23012,23039,23040,23373,25046 N450D,N450D,E484K,Q493R,Q493R,T604I,P1162S NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1811C>T,NC_045512.2:g.3484C>T YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Thr604Ile,YP_009724390.1:p.Pro1162Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22905 N448S NC_045512.2:g.1343A>G YP_009724390.1:p.Asn448Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22907 Y449H NC_045512.2:g.1345T>C YP_009724390.1:p.Tyr449His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22907 Y449N NC_045512.2:g.1345T>A YP_009724390.1:p.Tyr449Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912,22916 L452M,L452M NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912,22916 L452M,L452M NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.67 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Observed ~2x decrease on average in neutralization efficacy in convalescent sera of 16 health workers. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 3 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2/3 antibody C628 and class 2 antibody C643 selected for the emergence of the L452R mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021 https://doi.org/10.1101/2021.04.14.21255431 doi:10.1101/2021.04.14.21255431 33907767 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Ablation of neutralization capability of 3 of 4 convalescent sera tested, the other is significantly hindered. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~1.7-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 10 of 14 RBD-specific mAbs that showed at least 10-fold reduced neutralization of B.1.427/B.1.429 variant pseudotype (S13I, W152C, and L452R) were also found to poorly bind to just a L452R RBD mutant, demonstrating a role for this mutation as an escape mechanism for certain RBD-targeting mAbs. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion L452R derivative virus did not induce IFN-gamma expression even at the highest concentration tested (10 nM) in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456). Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects ~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking We observed increased entry by pseudoviruses carrying the L452R mutation compared to D614G alone, with a 6.7 to 22.5-fold increase in 293T cells and a 5.8 to 14.7-fold increase in human airway organoids. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.32 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02. Motozono 2021 https://doi.org/10.1016/j.chom.2021.06.006 doi:10.1016/j.chom.2021.06.006 34171266 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs X593 and P2B-2F6 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. [listed as L454R in Figure, but L452R in text, also text suggests not statistically significant, but error bars say otherwise in Figure 4] Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. L452R conferred about a two-fold reduction in neutralisation by vaccine sera, but was not statistically significant with this sample size. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~5x binding against this isolated mutation. Cligavimab lost ~4x binding against this isolated mutation. Regdanvimab lost ~4x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-02 and SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Increased stability of RBD expression in yeast, suggesting increased Spike protein stability. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012 L452R,L452R,L452R,E484K NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant combination shows a ~4-5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, same as L452R alone. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012 L452R,L452R,L452R,E484Q NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484Q had a ~5x drop in neutralization (vs ~10x for E484K). When E484Q and L452R were combined, the fold change was significant, but similar to that of L452R alone (~2x), suggesting no evidence for an additive effect [perhaps even E484Q effect dilution]. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.617) showed a 1.22x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2.5x. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.617) showed a 1.30x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.18x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x drop in neutralization (NT50) [working with the delins, less than just L452R but more than just E484Q]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x infectivity advantage to the spike particles [less than L452R or E484Q alone working with the delins]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Pseudotyped viruses for B.1.617 was 2.3-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. [details on the convalescent patient sera collection are not abundantly clear in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617) showed a 1.85x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The combination caused a 3-fold increase in infectivity relative to D614G wild type. [compare to 3.5x for L452R alone] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23604 L452R,L452R,L452R,E484Q,P681R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence Gross examination of 3+3 hamster lung specimens showed pronounced congestion and hemorrhages on days 5 and 7 post-infection in the case of the B.1.617.1 as compared with the B.1. The lung lesions with the B.1 variant were minimal to mild whereas with B.1.617.1 they were moderate. For B.1 pneumonic changes were minimal to mild (inflammatory cell infiltration, focal consolidation and mild congestion). The pronounced changes (moderate to severe) with mononuclear infiltration in the alveolar interstitial space, interstitial septal thickening, consolidation and pneumocyte hyperplasia were observed with B.1.617.1 variant consistently. Yadav 2021 https://doi.org/10.1101/2021.05.05.442760 doi:10.1101/2021.05.05.442760 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23604 L452R,L452R,L452R,E484Q,P681R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load In 9 infected hamsters each for B.1 and B.1.617.1, no significant change in viral load or subgenomic RNA levels were detected. Yadav 2021 https://doi.org/10.1101/2021.05.05.442760 doi:10.1101/2021.05.05.442760 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23604 L452R,L452R,L452R,E484K,P681R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant combination shows a ~3x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, significantly less of a decrease than any B.1.617 lineage variants alone, suggesting a synergistic effect on cell entry while maintaining known immunity esacpe mutants. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23604,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,P681R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Normalized for particle number, on ACE2.293T cells showed that the B.1.617 spike protein was >2-fold increase in infectivity relative to D614G wild type. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23060,23061,23062,23063 L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The presence of these B.1.417/B.1.429 defining variants in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021 https://doi.org/10.1101/2021.04.14.21255431 doi:10.1101/2021.04.14.21255431 33907767 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The L452R mutation increased the infectivity more than two-fold in these conditions. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2x. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 7.42x drop in neutralization (NT50) [mostly from 3 of the sera]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this RBD mutation conferred a 2.36x drop in neutralization (NT50). Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~2x infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 583 test-positive were Epsilon. Two dose vaccine efficacy against Epsilon was 97.6 (90.2-99.4%), one dose VE was 76.3 (48.1-89.1%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917 L452Q NC_045512.2:g.1355T>A YP_009724390.1:p.Leu452Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917 L452Q NC_045512.2:g.1355T>A YP_009724390.1:p.Leu452Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.27 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917,23027,23029,23030,23031,23399,23401,23402,23403 L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 3.4x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917,23027,23029,23030,23031,23399,23401,23402,23403 L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.038x fold change in IC50 in C.37 Lambda Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917,23027,23029,23030,23031,23399,23401,23402,23403 L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 1.7x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917,23027,23029,23030,23031,23399,23401,23402,23403 L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.048x fold change in IC50 in C.37 Lambda Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape VSV pseudotyped with Y453F reduced inhibition by most of the 13 potent convalescent serum/plasma samples tested, albeit with variable efficiency (median increase of serum/plasma titer required for 50% neutralization [NT50] = 1.62x, range = 1.02x to 3.43x), indicating that this RBD mutation may compromise SARS-CoV-2 control by preexisting neutralizing antibody responses. Hoffman 2021 https://doi.org/10.1016/j.celrep.2021.109017 doi:10.1016/j.celrep.2021.109017 33857422 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.25 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 10-fold reduction in binding efficiency vs wild type for MAb REGN10933. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~12x binding against this double mutation. Casirivimab lost ~64x binding against this double mutation. Cligavimab lost ~6x binding against this double mutation. Estesevimab lost ~10x binding against this double mutation. Imdevimab lost ~5x binding against this double mutation. Regdanvimab lost ~8x binding against this double mutation. Sotrovimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~4-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed in 4 separate mink farms in Denmark, and Y453F is circulating relatively widely in humans. Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 33172935 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02. Motozono 2021 https://doi.org/10.1016/j.chom.2021.06.006 doi:10.1016/j.chom.2021.06.006 34171266 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion The induction level of IFN-gamma expression by the Y453F derivative in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456) was significantly lower. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 33172935 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Casirivimab lost >50x binding against this mutation. Hoffman 2021 https://doi.org/10.1016/j.celrep.2021.109017 doi:10.1016/j.celrep.2021.109017 33857422 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 Y453F,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.1358A>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence "The so-called ""delta F"" variant combination previously observed in mink spillover events also emerged in a lymphoma patient (non-Hodgkin diffuse B-cell lymphoma IV stage B) with a long-term COVID-19 infection (4 months) where 18 de novo mutation occureed overall. Patient was taking rituximab, the B-cell-depleting agent, and had no detectable neutralizing antibody response." Bazykin 2021 https://virological.org/t/emergence-of-y453f-and-69-70hv-mutations-in-a-lymphoma-patient-with-long-term-covid-19/580 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22924,22925,22926 L455S,L455S,L455S NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.45 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22926,22927,22927,22928,22930,22930 F456L,F456L,F456L,F456L,F456L,F456L NC_045512.2:g.1366T>C,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>A,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>G,NC_045512.2:g.1368T>A YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects This double substitution reduces neutralization by RBD-specific mAbs from different clusters, specifically, the cluster I mAb COVA2-29, cluster III mAb COVA2-07 and cluster VI mAb COVA1-12. For COVA1-12 all neutralization activity is abolished, while COVA2-07 activity is just below the level required to calculate an IC50 value. Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22928 F456V NC_045512.2:g.1366T>G YP_009724390.1:p.Phe456Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22928 F456V NC_045512.2:g.1366T>G YP_009724390.1:p.Phe456Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Moderate in vitro selection against class 1 (Spike 'up' conformation) antibodies C683 and C664. Unclassified antibody C666 selected for the emergence of the F456V mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22928 F456V NC_045512.2:g.1366T>G YP_009724390.1:p.Phe456Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22936 K458N NC_045512.2:g.1374G>T YP_009724390.1:p.Lys458Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.09 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460Y NC_045512.2:g.1378A>T YP_009724390.1:p.Asn460Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460H NC_045512.2:g.1378A>C YP_009724390.1:p.Asn460His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Mild escape mutant emergent for class 1 antibody C613 in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460H NC_045512.2:g.1378A>C YP_009724390.1:p.Asn460His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460H NC_045512.2:g.1378A>C YP_009724390.1:p.Asn460His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22941 N460I NC_045512.2:g.1379A>T YP_009724390.1:p.Asn460Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22941 N460S NC_045512.2:g.1379A>G YP_009724390.1:p.Asn460Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22964 I468V NC_045512.2:g.1402A>G YP_009724390.1:p.Ile468Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22964 I468V NC_045512.2:g.1402A>G YP_009724390.1:p.Ile468Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22976 I472V NC_045512.2:g.1414A>G YP_009724390.1:p.Ile472Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22976 I472V NC_045512.2:g.1414A>G YP_009724390.1:p.Ile472Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to neutralizing mAb X593 (on D614G background) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C102, C105 and C144 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~50x binding against this isolated mutation. Estesevimab lost ~8x binding against this isolated mutation. Sotrovimab lost ~30x binding against this isolated mutation. Tixagevimab lost ~15x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some class 1 (Spike 'up' conformation) antibodies tested. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 host variant dependency This mutation's measured interaction affinity with ACE2:p.S19P (0.03% minor allele frequency, found almost exclusively in African/African-Americans in the GnomAD database) was significantly lower than the predicted value, indicating that these mutations were not independent. This is consistent with the fact that the ACE2 residue S19 is adjacent to RBD residue S477 in the contact interface. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 2.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects While S477N itself is highly resistent to a broad range of monoclonal antibodies, combined with S514F high neutralization is restricted to only three antibodies in a broad screen. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mixed bag of mild positive and negative changes in neutralization capability of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), 10 show low neutralization. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 11 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.22 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-07, SARS2-16 and SARS2-19 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility. Singh 2021 https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows some resistence across all antibodies tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility. Singh 2021 https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding, with increasing proportion in subsequent rounds. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-07 and SARS2-16 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,22995,23042 T478K,T478K,S494P NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1480T>C YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Combination of RBD mutations appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome complicated by diffuse alveolar hemorrhage, who was receiving anticoagulation therapy, glucocorticoids, cyclophosphamide, and intermittent rituximab and eculizumab. Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 33176080 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23012 S477N,E484K NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~10x binding against this double mutation. Tixagevimab lost ~16x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23402,23403 S477N,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was neutralized slightly less than D614G in 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23402,23403 S477N,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23402,23403 S477N,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence Compared to the clade 20A strains that predominated during phase 1 between March and May 2020, the Marseille-4 variant (characterized by this mutation plus N:p.M234I;A376T) was associated with a lower frequency of cough, rhinitis, and olfactory and gustatory disorders. By contrast, hypoxemia was more frequent in patients infected with the Marseille-4 variant. Fournier 2021 https://doi.org/10.1016/j.ijid.2021.03.068 doi:10.1016/j.ijid.2021.03.068 33785459 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23402,23403 S477N,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection "11 cases of re-infection with the ""Marseille-4"" variant found within 1028 positive tests, where all of the earlier infections were from different strains. This lineage is also characterized by N:p.M234I;A376T" Fournier 2021 https://doi.org/10.1016/j.ijid.2021.03.068 doi:10.1016/j.ijid.2021.03.068 33785459 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23003 N481Y NC_045512.2:g.1441A>T YP_009724390.1:p.Asn481Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Minor variant in initial round of in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009 V483L NC_045512.2:g.1447G>C YP_009724390.1:p.Val483Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, 1B07, SARS2-32, SARS2-35 and SARS2-07 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in all 4 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Remarkably, several of the E484 escape mutants were resistant to neutralization at the highest concentration (1:80 initial dilution) of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), all but one show major resistance. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23061,23062,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 152 virus from a chronically infected patient: although mAb C1A-B12 had no activity against this pseudotype, all three affinity optimized versions were active; the antibody containing the most mutations, C1A-B12.3, was the most potent (IC50 <0.5 μg/mL). Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23061,23062,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 152 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 152 S pseudotype was resistant to neutralization. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23061,23062,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This Spike pseudotype for Day 152 virus from a chronically infected patient was completely resistent to REGN10933. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2). Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous. Braeye 2022 https://doi.org/10.1101/2022.05.09.22274623 doi:10.1101/2022.05.09.22274623 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2). Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2). Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness 3rd exposure to antigen by Delta (B.1.617.2) (n=24) breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a 3rd mRNA vaccine dose in individuals aged 21 –63 years, median age=30 years. Data collected 5.5 months after 2nd vaccination. Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous. Braeye 2022 https://doi.org/10.1101/2022.05.09.22274623 doi:10.1101/2022.05.09.22274623 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In sera from 17 sero-positive blood donors, and 18 months post-infection (May 2020) sera from 17 health care workers in Sweden, a 40x drop in neutralization by Omicron (B.1.1.529) pseudotyped lentivirus was observed in HEK293T cells using the First WHO International Standard (20/136). Median IC50 reduction was ~6x for the blood donors, and ~4.5x for the health care workers. Sheward 2021 https://drive.google.com/file/d/1CuxmNYj5cpIuxWXhjjVmuDqntxXwlfXQ/view False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23071,23074,23075,22992,23060,23061,23062,23063 E484A,E484A,E484A,E484A,Y505H,Y505H,Y505H,S477N,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1430G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using molecular dynamics simulation, ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations. Zhang 2022 https://doi.org/10.1101/2022.06.05.493249 doi:10.1101/2022.06.05.493249 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding The only mutation in the B.1.351 lineage that appears to contribute to neutralization reduction (~1.7x across 10 convalescent sera from April 2020 infectees) Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The neutralizing activity of 15/20 convalescent sera was significantly lower against this pseudotyped virus model Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2 antibodies C627, C602, C671, C643, and class 2/3 antibody C603 selected for the emergence of the E484K mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.3x reduction in IC50 serum dilution concentration for 6 convalescent sera." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers of non-human primate sera after one or two doses of Ad26.COV2.S (Jannsen vaccine) against the variants containing the E484K substitution in the RBD were present but reduced (fold reduction between 3.35–7.78, 95% confidence interval all above twofold difference, one-sample t test). Solfrosi 2021 https://doi.org/10.1084/jem.20202756 doi:10.1084/jem.20202756 33909009 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-02, 1B07, SARS2-16, SARS2-32, SARS2-35 and 2B04 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Multiple individuals in two related households were infected with a newly acquired E484K mutation within the B.1.311 lineage. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient's quarantine period. Sabin 2021 https://doi.org/10.1101/2021.10.02.21264415 doi:10.1101/2021.10.02.21264415 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Of 50 mAbs tested, major loss of neutralization observed for S2N28, S2X615, S2N12, S2X192, S2H7, S2X16, S2X58, S2H70, S2X613, S2D19, S2N22, S2D32, S2H58, S2M11, S2D106, S2X30. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Monoclonal antibodies 13G9 and 58G6 maintain fairly high neutralization potency, compared to others interfacing with E484K. Li 2021 https://doi.org/10.1101/2021.04.19.440481 doi:10.1101/2021.04.19.440481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Analyzing responses to the E484K mutation seen in B.1.351 and P.1 variants, we noted that it did not fall in a region predicted to bind the HLAII alleles tested (table S4). The mutation appeared to have no substantial or differential impact on T cell responses. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Human sera from 5 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) neutralized this variant 3.4x less relative to reference USA-WA1/2020 strain. 8 convalescent plasma with weak IgG ELISA titre neutralized this variant 2.4x less relative to reference USA-WA1/2020 strain. One plasma failed to neutralize at all. 11 convalescent plasma with moderate IgG ELISA titre neutralized this variant 4.2x less relative to reference USA-WA1/2020 strain. 11 convalescent plasma with high IgG ELISA titre neutralized this variant 2.6x less relative to reference USA-WA1/2020 strain. Jangra 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~20x binding against this isolated mutation. Casirivimab lost ~4x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484K conferred a ten-fold reduction in neutralisation by vaccine sera. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~16x binding against this isolated mutation. Casirivimab lost ~16x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 3 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, E484Q shows a notably resistant profile, comparable to or even more resistant than E484K at later time points (i.e. more resistant to immune cell somatic mutation evolution), see Figure 5a,b. Subject C 32 days post-infection showed >>10 fold reduction in neutralization, reducing to ~10-fold by day 104. Subject B 26 days post-infection showed ~10 fold reduction in neutralization, reducing to ~4x at day 113. Notably, Subject B also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 32, and no E484K immune escape at day 104. Subject I 26 days post-infection showed ~10 fold reduction in neutralization, with no reduction in escape at day 102. Notably, Subject I also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 26, and no E484K immune escape at day 102. Greaney 2021 https://doi.org/10.1016/j.chom.2021.02.003 doi:10.1016/j.chom.2021.02.003 33592168 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in all 4 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Individual variants appearing at <=30% frequency at day 21 in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then appearing all at >95% frequency at day 27. Chen 2021 https://doi.org/10.1101/2021.04.08.21254791 doi:10.1101/2021.04.08.21254791 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.6 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported moderate increase in affinity compared to wild-type RBD on the cell surface (Kd = 38.5nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy E484K pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed a mean 2.8x decrease in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects >20% (ELISA significance threshold) drop in antibody binding by this variant against monoclonal antibody VH-Fc ab8. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant alone shows a 10x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus) Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody VH-Fc ab8 Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus) Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, ELISA tests show 10x reduced efficacy of a majority of isolated antibodies, but only a modest decrease for vaccine plasma overall. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape As measured by surface plasmon resonance, RBD with the E484K mutation alone showed a mean 19.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma. Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape This mutation occurred in 100% of sequenced virions after 12 passages and led to a 4-fold decrease in convalescent plasma neutralization activity Andreano 2020 https://doi.org/10.1101/2020.12.28.424451 doi:10.1101/2020.12.28.424451 33398278 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in binding efficiency vs wild type for mAb LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape due to E484K [given Dec 2020-Apr 2021 time frame of the study, this is assumed to entail both Beta and Gamma lineages]. Chung 2021 https://doi.org/10.1136/bmj.n1943 doi:10.1136/bmj.n1943 34417165 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,22597,22599 E484K,R346K,R346K NC_045512.2:g.1450G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E484K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,22810,22811,22812,22813,22813 E484K,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~32x binding against this double mutation. COR-101 lost ~160x binding against this double mutation. Casirivimab lost ~16x binding against this double mutation. Estesevimab lost ~32x binding against this double mutation. Regdanvimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403 E484K,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~13x more infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,22810,22811,22812,22813,22813,23399,23401,23402,23403 E484K,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Approximately as infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of the individual variants). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23053,23054,23055,23060,23061,23062,23063 E484K,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.4 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.5 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.4 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~17.5x folds more significant in 9 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Values taken 28 days after booster dose was given for BBIBP-CorVvaccine to 390 participants with 130 participants in the 0-14d-10m, 0-21d-10m and 0-28d-10m group. The geometric mean titers (GMT) of neutralizing antibody in 0-28d-10m and 0-21d-10m group were significantly higher than 0-14d-10m group at month 3, month 6 and month 10 after the second dose. A sharply decrease by 4.85-fold (GMT: 94.4-20.3), 4.67-fold (GMT: 134.4-28.8) and 4.49-fold (GMT: 145.5-32.4) was observed from day 28 to month 10 after the second dose in 0-14d-10m, 0-21d-10m and 0-28d-10m group, respectively, and they had similar decline kinetics. Yao T 2022 https://doi.org/10.1101/2022.06.22.22276690 doi:10.1101/2022.06.22.22276690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Omicron neutralizing antibodies is 0.686x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~100x folds more significant in 3 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Viral load from oral swabs from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Viral load from lung tissue from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)] Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)] Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Protection against symptomatic infection caused by Beta/Gamma (assumed by combined presence of N501Y and E484K) was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%). Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Omicron neutralizing antibodies is 0.722x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 20 sera from BNT162b2 mRNA vaccine inoculated participants, 6 displayed mild (2x) reductions in neutralization. This variant combination showed the highest reduction, but the magnitude of the differences was small compared to the >4x differences in HA-inhibition titers that have been used to signal potential need for a strain change in influenza vaccines. Xie 2021 https://doi.org/10.1038/s41591-021-01270-4 doi:10.1038/s41591-021-01270-4 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In the case of VOC B.1.1.7+E484K, the addition of the E484K mutation to N501Y further increased the affinity, to ~15 fold higher than WT RBD (KD ~5 nM), by further increasing the k(on) as measured by surface plasmon resonance. Because the higher k(on) could result in mass transfer limiting binding, we confirmed that the kinetic measurement for this variant was not substantially affected by varying levels of immobilization. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.0015x fold change in IC50 in B.1.1.529 Omicron Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.025x fold change in IC50 in B.1.1.529 Omicron Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Omicron Molnupiravir (MK-4482) had no statistically significant change. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.5 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~11x, Vero ~10x, and Calu-3 ~11x. Compare to wild type at ~5x across cell types. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~12x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of 501 and 484). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~6x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied] Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation ~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Pseudotyped viruses for B.1.618 was 2.5-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. [details on the convalescent patient sera collection are not abundantly clear in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, RBD-specific mutation E484Q did not significantly confer infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 1.34x drop in neutralization (NT50) [mostly from a single serum]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.618 was 2.7-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 3-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~4x infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The estimated vaccine effectiveness against R.1 strain SARS-CoV-2 infection among residents in a Kentucky skilled nursing facility was 66.2% (95% CI = 40.5%–80.8%) and among health care workers was 75.9% (95% CI = 32.5%–91.4%) in the cohort of only those 14d+ post-vaccination Pfizer booster dose. VE against symptomatic COVID-19 was 86.5% (95% CI = 65.6%–94.7%) among residents and 87.1% (95% CI = 46.4%–96.9%) among HCP. VE against hospitalization was 94.4% (95% CI = 73.9%–98.8%) among residents; no HCP were hospitalized. Three residents died, two of whom were unvaccinated (VE = 94.4%; 95% CI = 44.6%–99.4%). Cavanaugh 2021 https://doi.org/10.15585/mmwr.mm7017e2 doi:10.15585/mmwr.mm7017e2 33914720 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403,25088 E484K,D614G,D614G,D614G,D614G,V1176F NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs] Sapkal 2021 https://doi.org/10.1101/2021.04.30.441559 doi:10.1101/2021.04.30.441559 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403,25088 E484K,D614G,D614G,D614G,D614G,V1176F NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs] Sapkal 2021 https://doi.org/10.1101/2021.04.30.441559 doi:10.1101/2021.04.30.441559 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403,25088 E484K,D614G,D614G,D614G,D614G,V1176F NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the P.1 & P.2 lineages of SARS-CoV-2 in Brazil. The Brazilian arm of the Phase 3 double blind study showed severe/critical disease VE of 81.9% (95% CI: 17.0-98.1), and moderate to severe/critical disease VE of 66.2% (95% CI: 51.0-77.1). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 69.3% of mostly severe infections sequenced as of this report, 69.4% were of P.2 lineage [defining lineage SNPs reported here]. 2021 https://www.fda.gov/media/146217/download False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403,25088 E484K,D614G,D614G,D614G,D614G,V1176F NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped P.2 virus has reduced neutralization activity vs wild type: 5.8x (30 sera Pfizer median 9 days post 2nd dose) and 2.9x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23013 E484V NC_045512.2:g.1451A>T YP_009724390.1:p.Glu484Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23013 E484V NC_045512.2:g.1451A>T YP_009724390.1:p.Glu484Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23013 E484V NC_045512.2:g.1451A>T YP_009724390.1:p.Glu484Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486I NC_045512.2:g.1456T>A YP_009724390.1:p.Phe486Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486I NC_045512.2:g.1456T>A YP_009724390.1:p.Phe486Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486I NC_045512.2:g.1456T>A YP_009724390.1:p.Phe486Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2:g.1456T>C YP_009724390.1:p.Phe486Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2:g.1456T>C YP_009724390.1:p.Phe486Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed in 4 separate mink farms in Denmark, but not humans, potential adaptation (diff set of farms than N501T). Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 33172935 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2:g.1456T>C YP_009724390.1:p.Phe486Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutation causes a greater than 100x fold change in IC50 of Ensovibep. Rothenberger 2021 https://doi.org/10.1101/2021.02.03.429164v4 doi:10.1101/2021.02.03.429164v4 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutation causes a greater than 100x fold change in IC50 of Ensovibep. Rothenberger 2021 https://doi.org/10.1101/2021.02.03.429164v4 doi:10.1101/2021.02.03.429164v4 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape IC50 relative to wildtype drops ~8x in neutralization efficiency between 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 1 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects >60% drop in antibody binding (ELISA) by this variant against monoclonal antibody VH-Fc ab8. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 5 antibodies. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.13 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-07, SARS2-19, 1B07, SARS2-16 and 2B04 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed striking resistance with only 38% neutralization at the highest concentration tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Modest decrease in in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23023 N487K NC_045512.2:g.1461T>G YP_009724390.1:p.Asn487Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, high ACE2 binding affinity loss Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Based on structural modelling, this change detected on day 128 sequencing in a chronically infected patient would alter an extensive network of polar interactions with antibody residue R94VH, a germline antibody residue that is conserved in all of the potent VH3-53/3-66-derived antibodies isolated from a convalescent donor 5 weeks after infection. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.11 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-32. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 3 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody ab8 Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2/3 mAb C603 modestly selected for the emergence of this mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (3 ablations). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23060,23061,23062,23063 Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This Spike pseudotype for Day 146 virus from a chronically infected patient was completely resistent to REGN10933. The variant had a 4-fold decrease in REGN10987 neutralization sensitivity (2nd component of the Regeneron mAb cocktail). Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23060,23061,23062,23063 Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 146 virus from a chronically infected patient: resistant to neutralization by mAb C1A-B12, and was still resistant to the affinity enhanced antibodies derived from it (i.e. no affinity maturation effect on neutralization). Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23060,23061,23062,23063 Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 146 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 146 S pseudotype was resistant to neutralization. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490V NC_045512.2:g.1468T>G YP_009724390.1:p.Phe490Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) resistant to 3 individual sera at >4x Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs X593, 261-262, H4, and P2B-2F6 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody ab8 Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Positive selection (up to 23% of supernatant sequences) after C121 monoclonal antibody assay Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in binding efficiency vs wild type for mAbs CB6/LY-CoV16 and LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2 mAb C627 modestly selected for the emergence of this mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Dominant (70%) in day 21 of prolonged infection in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then nearly disappearing (<5%) by day 27. Chen 2021 https://doi.org/10.1101/2021.04.08.21254791 doi:10.1101/2021.04.08.21254791 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 2 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, S484P shows a slightly resistant profile across both timepoints (i.e. resistant to immune cell somatic mutation evolution) Greaney 2021 https://doi.org/10.1016/j.chom.2021.02.003 doi:10.1016/j.chom.2021.02.003 33592168 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-01 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Minor variant selected in late rounds of an in vitro evolution experiment for ACE2 binding. Shown to increase the thermostability but decrease the association rate constant of the RBD to ACE2 Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using molecular dynamic simulation, the mildly (~1kcal/mol) enhanced binding energy of this variant is primarily contributed by Tyr505 (−4.98 kcal/mol) which is now involved in a strong hydrogen bonding network with Arg393. Another important energetic contribution comes from the altered orientation of Tyr41 which is now involved with two hydrogen-bonding interactions with Asp355 and Thr500. 2021 https://doi.org/10.1016/j.bbrc.2021.01.035 doi:10.1016/j.bbrc.2021.01.035 33602511 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Regdanvimab lost ~32x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23048 G496S NC_045512.2:g.1486G>A YP_009724390.1:p.Gly496Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23053,23054,23055,23060,23061,23062,23063 Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. The extent of affinity increase with Q498R and N501Y is not exactly quantified, as E484K always emerged with this duo during in vitro evolution. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 33176080 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~8x binding against this isolated mutation. Regdanvimab lost ~6x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy Variant within the six key residues in the receptor binding domain (RBD). Independently reported in UK, Australia (same origin as UK), and South Africa (independent origin). Flores-Alanis 2021 https://doi.org/10.3390/pathogens10020184 doi:10.3390/pathogens10020184 33572190 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C663, and to a lesser extent C613. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Utilizing shark derived vnarbodies, S375F mutation on Omicron RBD disrupts the structure of β-strand, which inhibits binding with 20G6. 20G6 binds to a hidden epitope on RBD which is highly conserved in sarbecoviruses. Feng 2022 https://doi.org/10.1002/smtd.202200387 doi:10.1002/smtd.202200387 35583124 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.2x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 and day 14 post-2nd dose) against a recombinant single variant virus (modified replicating WA-1 cDNA clone) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.69 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape by lineage Alpha [defined here as N501Y positive, but E484K negative]. Chung 2021 https://doi.org/10.1136/bmj.n1943 doi:10.1136/bmj.n1943 34417165 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In 30 samples collected 111 to 260 days post onset of symptoms, the covalescent plasma can neutralize both the reference USA-WA1/2020 strain and the mouse adapted strain that contains the N501Y spike mutation with similar efficiency. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The N501Y mutation had the biggest effect on ACE2 affinity of any VOC mutation tested, increasing the affinity ~10 fold to KD ~7 nM, by increasing the k(on) ~1.8 fold and decreasing the k(off) by ~ 7 fold as measured by surface plasmon resonance. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021 https://doi.org/10.1101/2021.04.14.21255431 doi:10.1101/2021.04.14.21255431 33907767 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a modest decrease in neutralization by vaccine plasma was observed. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Human sera from 6 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) can neutralize both the reference USA-WA1/2020 strain and the mouse adapted SARS-CoV-2 strain that contains the N501Y spike mutation with similar efficiency. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape As measured by surface plasmon resonance, RBD with the N501Y mutation alone showed a mean 2.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma. Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021 https://doi.org/10.1101/2021.02.02.428884 doi:10.1101/2021.02.02.428884 33564771 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x) Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation alone accounts for most of the increased infectivity of the Alpha variant, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters, and Vero E6 (NHP) and Calu-3 (human) cell lines. Liu 2021 https://doi.org/10.1101/2021.03.08.434499 doi:10.1101/2021.03.08.434499 33758836 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021 https://doi.org/10.1101/2021.02.02.428884 doi:10.1101/2021.02.02.428884 33564771 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021 https://doi.org/10.1101/2021.02.02.428884 doi:10.1101/2021.02.02.428884 33564771 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Lowered the neutralization potency of mAb COVA1-12 to the limit of the assay. Decrease in potency was observed against the N501Y pseudotype for the cluster IX mAb COVA2-17." Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Vaccinated, but not post-infection sera, show decreased average T cell response to an N501Y peptide. When we primed transgenic mice expressing human HLA-DRB1*0401 with the Wuhan Hu-1 peptide pool, T cell responses to the B.1.1.7 variant peptide pool were significantly reduced (p = 0.0286). Furthermore, the T cell response to the spike N501Y mutation common to all three of the current VOC was ablated. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~4-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~4-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In silico methods (PyMOL and PDBePISA) involving mutagenesis (N501Y mutation) and interface analysis focusing on the Spike RDB-ACE2 interaction showed that the SARS-CoV-2 N501Y mutant (lineage B.1.1.7) establishes a more significant number of interactions relating to the mutant residue Y501 (Spike RDB) with residues Y41 and K353 (ACE2). This finding shows that the increased infectivity of SARS-CoV-2 lineage B.1.1.7 is associated with the interaction force between the Spike RBD Y501 mutant residue with the ACE2 receptor, which in this strain is increased. 2021 https://doi.org/10.1101/2020.12.29.424708 doi:10.1101/2020.12.29.424708 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Of 50 mAbs tested, major loss of neutralization observed for S2X128, S2D8, S2X192, S2D19, S2H14, S2H19. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x) Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Contrary to other reports on N501Y containing lineages (i.e. with additional mutations), N501Y alone may have an even greater affinity for a human monoclonal antibody specific for wild type. These results suggest that the individual N501Y mutation does not contribute to altered viral properties by itself, but may contribute to a collective conformational shift produced by multiple mutations. Klegerman 2021 https://doi.org/10.1101/2021.04.26.441517 doi:10.1101/2021.04.26.441517 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity. Zhu 2021 https://doi.org/10.1101/2021.01.11.426269 doi:10.1101/2021.01.11.426269 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021 https://doi.org/10.1101/2021.02.02.428884 doi:10.1101/2021.02.02.428884 33564771 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity. Zhu 2021 https://doi.org/10.1101/2021.01.11.426269 doi:10.1101/2021.01.11.426269 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021 https://doi.org/10.1101/2021.02.02.428884 doi:10.1101/2021.02.02.428884 33564771 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM). Ramanathan 2021 https://doi.org/10.1101/2021.02.22.432359 doi:10.1101/2021.02.22.432359 33655251 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM). Ramanathan 2021 https://doi.org/10.1101/2021.02.22.432359 doi:10.1101/2021.02.22.432359 33655251 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slightly increased infection rate amongst the cells. [in what is essentially a replicate experiment in the same paper, because each B.1.351 lineage variant was independetly evaluated and N501 is in both lineages, a significant decrease was observed, therefore the error bars described in this paper should be interpreted carefully] Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The most frequent RBM mutation N501Y (165,519 instances) makes defective the atypical N-glycosylation sequon NGV 501-503, becoming a key RBM position for the interaction with hACE2-binding hotspot 353. Gamez 2021 https://doi.org/10.1101/2021.04.09.439154 doi:10.1101/2021.04.09.439154 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape 0.7x reduction in neutralization by key variant in several variants of concern in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity. Zhu 2021 https://doi.org/10.1101/2021.01.11.426269 doi:10.1101/2021.01.11.426269 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,22810,22811,22812,22813,22813 N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~20x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~6x binding against this double mutation. M396 lost ~10x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,22810,22811,22812,22813,22813,23012 N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In post-vaccination sera from individuals who received one (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) of the BNT162b2 Pfizer vaccine, an average 6.8x reduction in neutralization efficacy of this B.1.351 key variants pseudotype lentivirus vs D614G was observed. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,22810,22811,22812,22813,22813,23012 N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape ~7x reduction in neutralization by key B.1.351 lineage RBD variant combination in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Two of the cohort showed no neutralization against this variant. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23012 N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~64x binding against this double mutation. COR-101 lost ~50x binding against this double mutation. Casirivimab lost ~250x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~32x binding against this double mutation. Tixagevimab lost ~10x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23271 N501Y,N501Y,N501Y,N501Y,A570D NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Partial sequencing of S gene reveals two cases of probable early 2021 B.1.1.7 lineage reinfection from non-B.1.1.7 original cases in Lombardy, with 45 to 90 days between infections (less than the typical 90 day guideline for this call). Patients were 56 and 58yo, immunocompenent, with one a former smoker with obesity and dyslipidemia. One case required intubation during first infection, but presented with mild symptoms upon reinfection. The other case convalesced at home during the first episode, but required CPAP support in the subacute clinical unit upon reinfection. Novazzi 2021 https://doi.org/10.1002/jmv.27066 doi:10.1002/jmv.27066 33969504 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation ~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~9x, Vero ~8x, and Calu-3 ~8x. Compare to wild type at ~5x across cell types. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~13x, Vero ~10x, and Calu-3 ~10x. Compare to wild type at ~5x across cell types. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking 9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking 9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed no change in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding "Lentiviral pseudotyped with the key mutations from COH.20G/677H (""Ohio"") lineage was neutralized similarly to D614G in 10 convalescent sera from April 2020 infectees." Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells for ACE2 affinity changes vs D614G alone, showing a ~70% drop in IC50 (i.e. increased affinity). Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23521,23522,23524,23525 N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23071,23074,23075 Y505H,Y505H,Y505H NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed first in a single tiger (cohort of 5), potential adaptation. McAloose 2020 https://doi.org/10.1128/mBio.02220-20 doi:10.1128/mBio.02220-20 33051368 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23071,23074,23075 Y505H,Y505H,Y505H NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23102 S514T NC_045512.2:g.1540T>A YP_009724390.1:p.Ser514Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23108 E516Q NC_045512.2:g.1546G>C YP_009724390.1:p.Glu516Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23115 L518Q NC_045512.2:g.1553T>A YP_009724390.1:p.Leu518Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23120 A520S NC_045512.2:g.1558G>T YP_009724390.1:p.Ala520Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness CR3022 (SARS-targeting mAb) cross-reactivity lost ~4x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23148 K529T NC_045512.2:g.1586A>C YP_009724390.1:p.Lys529Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.15 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing statistically significant increased infection rate amongst the cells. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated that there is very little free energy change (ddG. -0.02 kcal/mol) for this variant (i.e. approx. same stability as wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant raises PIWAS epitope score from 3.6% to 6.2% (improved immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23373 T604I NC_045512.2:g.1811C>T YP_009724390.1:p.Thr604Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a lentivirus virus pseudotyped with D614G Spike, sera from vaccinated individuals who received the second dose (9–11 days post-second dose of Pfizer) exhibited a robust neutralizing potential, with a mean NT50 value of 99,000. This was an average of a 2-fold increase, relative to sera drawn from the individuals who received one dose of vaccination—mean NT50 dilution of 51,300. Importantly, a 6-fold increase in mean NT50 dilution was obtained when sera from the first vaccination dose was compared to convalescent sera from cohort with severe disease (NT50 51,000 vs 8,700) 21 to 63 days post-onset. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 2.5 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to wild type, D614G showed increased infectivity (ie. cold stability) after storage at -20°C for up to 30 days. Huang 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped D614G virus has reduced neutralization activity vs wild type: 1.2x (37 sera Pfizer median 9 days post 2nd dose, 37 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.05x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.45x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.43x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 1.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In four cell lines (including 293T-hACE2 cells), this mutation combination increases infectivity vs D614G alone Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Yurkovetskiy 2020 https://doi.org/10.1016/j.cell.2020.09.032 doi:10.1016/j.cell.2020.09.032 32991842 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events "This mutation (a.k.a. ""Doug"") outside the receptor binding domain, while highly favorable to improved human-human transmission, decreases transduction in naked mole-rat (Heterocephalus glaber) fibroblast and Japanese pipistrelle bat (Pipistrellus abramus) cell cultures using a pseudotyped VSV assay." Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Weissman 2020 https://doi.org/10.1101/2020.07.22.20159905 doi:10.1101/2020.07.22.20159905 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 conferred a nearly two-fold infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD mutation conferred a 4.85x drop in neutralization (NT50). Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Yurkovetskiy 2020 https://doi.org/10.1016/j.cell.2020.09.032 doi:10.1016/j.cell.2020.09.032 32991842 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Weissman 2020 https://doi.org/10.1101/2020.07.22.20159905 doi:10.1101/2020.07.22.20159905 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Yurkovetskiy 2020 https://doi.org/10.1016/j.cell.2020.09.032 doi:10.1016/j.cell.2020.09.032 32991842 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.35x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission. Plante 2020 https://doi.org/10.1038/s41586-020-2895-3 doi:10.1038/s41586-020-2895-3 33106671 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses. Ozono 2020 https://doi.org/10.1038/s41467-021-21118-2 doi:10.1038/s41467-021-21118-2 33558493 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses. Ozono 2020 https://doi.org/10.1038/s41467-021-21118-2 doi:10.1038/s41467-021-21118-2 33558493 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Studying 94 COVID-19 extended infection cases with genomics April 1 to October 17, 2020, one case developed 23 mutations in a 19 day period, including this combination in Spike. Landis 2021 https://doi.org/10.1101/2021.05.08.21256775 doi:10.1101/2021.05.08.21256775 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking The increased transduction with Spike D614G ranged from 1.3- to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2 and from 1.5- to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction. Daniloski 2021 https://doi.org/10.7554/eLife.65365 doi:10.7554/eLife.65365 33570490 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.97x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a slight decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.53x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575 D614G,D614G,D614G,D614G,L5F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.1x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575 D614G,D614G,D614G,D614G,L5F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.23x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575 D614G,D614G,D614G,D614G,L5F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664 D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.526) showed a 1.02x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664 D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.526) showed a 1.78x increase in binding (KD) relative to D614G, even though each variant independently decreases binding. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664 D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.526) showed a 1.34x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600 D614G,D614G,D614G,D614G,S13I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600 D614G,D614G,D614G,D614G,S13I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.42x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600 D614G,D614G,D614G,D614G,S13I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600,22018,22915,22916,22917 D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. [Stark contrast to 2.15x increase in binding by convalescent plasma 8 months post infection, presumably via memory B cell affinity maturation against L452R effects] 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600,22018,22915,22916,22917 D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.429 aka Epsilon) showed a 2.82x increase in binding (KD) relative to D614G, indicating a strong marginal effect for L452R. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600,22018,22915,22916,22917 D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, indicating ablated marginal effect from L452R. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614 D614G,D614G,D614G,D614G,L18F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.07x decrease in binding (KD) relative to D614G. Compare to increased binding in full Spike variant complements for major lineages containing this variant subset: 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614 D614G,D614G,D614G,D614G,L18F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.66x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Compare to decreased binding in full Spike variant complements for major lineages containing this variant subset: 0.96x (B.1.351 aka Beta), 0.77x (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614 D614G,D614G,D614G,D614G,L18F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.30x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.28x increase (B.1.351 aka Beta), and 1.14x decrease (P.1 aka Gamma). 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.17x increase (B.1.351 aka Beta), and 1.47x decrease (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing P.1 aka Gamma) showed a 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing P.1 aka Gamma) showed a 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing P.1 aka Gamma) showed a 4.24x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664 D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing B.1.351 aka Beta) showed a 1.04x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, in contrast to the largely positive binding values for each individual mutation that comprises the set. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664 D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing B.1.351 aka Beta) showed a 1.28x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. It shows a 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664 D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.351 aka Beta) showed a 3.56x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21621 D614G,D614G,D614G,D614G,T20N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.39x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21621 D614G,D614G,D614G,D614G,T20N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.96x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21621 D614G,D614G,D614G,D614G,T20N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21638 D614G,D614G,D614G,D614G,P26S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.58x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21638 D614G,D614G,D614G,D614G,P26S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.23x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21638 D614G,D614G,D614G,D614G,P26S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.33x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.51x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing B.1.1.7 aka Alpha) showed no change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.28x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing B.1.1.7 aka Alpha) showed a 1.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.1.7 aka Alpha) had 5.43x increased binding relative to D614G alone. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21801 D614G,D614G,D614G,D614G,D80A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination showed no change relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21801 D614G,D614G,D614G,D614G,D80A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.64x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.35x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21801 D614G,D614G,D614G,D614G,D80A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21846 D614G,D614G,D614G,D614G,T95I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21846 D614G,D614G,D614G,D614G,T95I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21846 D614G,D614G,D614G,D614G,T95I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21974 D614G,D614G,D614G,D614G,D138Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21974 D614G,D614G,D614G,D614G,D138Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21974 D614G,D614G,D614G,D614G,D138Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.32x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22018 D614G,D614G,D614G,D614G,W152C NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.15x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22018 D614G,D614G,D614G,D614G,W152C NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22018 D614G,D614G,D614G,D614G,W152C NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.03x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22132 D614G,D614G,D614G,D614G,R190S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.59x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22132 D614G,D614G,D614G,D614G,R190S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.82x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22132 D614G,D614G,D614G,D614G,R190S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22206 D614G,D614G,D614G,D614G,D215G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.19x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22206 D614G,D614G,D614G,D614G,D215G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.79x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22206 D614G,D614G,D614G,D614G,D215G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D253G,D253G,D253G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D253G,D253G,D253G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.08x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D253G,D253G,D253G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22810,22811,22812,22813,22813 D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22810,22811,22812,22813,22813 D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.76x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.75x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22810,22811,22812,22813,22813 D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22812 D614G,D614G,D614G,D614G,K417T NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.28x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22812 D614G,D614G,D614G,D614G,K417T NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22812 D614G,D614G,D614G,D614G,K417T NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.66x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.05x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.16x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 6.2-fold lower (95% CI: 11.8x-14.3x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 4.2x-fold lower (95% CI: 0.15x-0.20x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy paired testing of vaccine sera against ancestral virus compared to Omicron BA.1 shows that 3-dose vaccine regimen provides over 50x fold increase in protection against Omicron(B.1.1.529 [BA.1]) compared to a 2-dose regimen. Hao 2022 https://doi.org/10.1101/2022.08.12.22278720 doi:10.1101/2022.08.12.22278720 36032965 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 28.7x-fold lower (95% CI: 0.03x-0.05) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness 4th antigenic exposure with Omicron (B.1.1.529 [BA.1])(n=29) infection increased variant specific plasma antibody and memory B cell responses as well as overall increased strain specific memory in individuals aged 22 –79 years, median age=33.5 years. Data collected 2.4 months after 3rd vaccination. Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 3.4-fold lower (95% CI: 3.2x-3.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 3.9x-fold lower (95% CI: 0.14x-0.17x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 78fM for binding to the Omicron BA.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 4.5-fold lower (95% CI: 4.3x-4.7x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 4.2-fold lower (95% CI: 5.8x-6.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 3.9x-fold lower (95% CI: 0.14x-0.18x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23012 D614G,D614G,D614G,D614G,E484K NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.42x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23012 D614G,D614G,D614G,D614G,E484K NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23012 D614G,D614G,D614G,D614G,E484K NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This variant appears twice in the experiments, with slightly different affinities (both ~1.2x decrease in binding relative to D614G) using flow cytometry and ACE2 ectodomains-Fc portion IgG complex. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23060,23061,23062,23063 D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23060,23061,23062,23063 D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23060,23061,23062,23063 D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.52x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis). Compare to full Spike variant complements for major lineages containing this variant subset: 5.43x (B.1.1.7 aka Alpha), 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23271 D614G,D614G,D614G,D614G,A570D NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23271 D614G,D614G,D614G,D614G,A570D NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23271 D614G,D614G,D614G,D614G,A570D NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.18x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23521,23522,23524,23525 D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23521,23522,23524,23525 D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.21x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23521,23522,23524,23525 D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.48x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23604 D614G,D614G,D614G,D614G,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant change in virus neutralzation by 18 Pfizer two dose vaccinee sera compared to B.1.1.7. [results without including the used mutation A27S likely generalizable, as this is not a lineage defining mutation] Zuckerman 2021 https://doi.org/10.1101/2021.03.25.21253908 doi:10.1101/2021.03.25.21253908 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23604 D614G,D614G,D614G,D614G,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.26x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23604 D614G,D614G,D614G,D614G,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23604 D614G,D614G,D614G,D614G,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23664 D614G,D614G,D614G,D614G,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23664 D614G,D614G,D614G,D614G,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23664 D614G,D614G,D614G,D614G,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed essentially no change in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23709 D614G,D614G,D614G,D614G,T716I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.12x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23709 D614G,D614G,D614G,D614G,T716I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23709 D614G,D614G,D614G,D614G,T716I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.58x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24506 D614G,D614G,D614G,D614G,S982A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24506 D614G,D614G,D614G,D614G,S982A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.3x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24506 D614G,D614G,D614G,D614G,S982A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24642 D614G,D614G,D614G,D614G,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.69x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24642 D614G,D614G,D614G,D614G,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.22x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24642 D614G,D614G,D614G,D614G,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.56x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24914 D614G,D614G,D614G,D614G,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24914 D614G,D614G,D614G,D614G,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24914 D614G,D614G,D614G,D614G,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.96x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23429 A623T NC_045512.2:g.1867G>A YP_009724390.1:p.Ala623Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23522,23524,23525 H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23522,23524,23525 H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain increases the virus transduction rate in tree shrew (Tupaia belangeri), (as it does in humans) according to pseudotyped VSV experiments. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23522,23524,23525 H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.87 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23522,23524,23525 H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Six minks were intranasally infected with WA1 isolate, all developed this mutation during infection. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23587,23587 Q675H,Q675H NC_045512.2:g.2025G>C,NC_045512.2:g.2025G>T YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly enhanced the ability of the pseudotyped VSV to infect fat-tailed gerbil (Pachyuromys duprasi) kidney cell cultures, with a transduction rate of 13.4%, close to the 15.7% in epithelial-like human Huh-7 cells while starting from a significantly lower wildtype (Wuhan-Hu-1 Spike VSVdeltaG psuedotype) rate. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681R NC_045512.2:g.2042C>G YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. [PG: Inferred by conservative AA substitution of described P681H] Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic. Johnson 2020 https://doi.org/10.1101/2020.08.26.268854 doi:10.1101/2020.08.26.268854 32869021 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In the absence of N501Y, this Alpha lineage change in the furin clevage site did NOT show significant increase in infectivity relative to wild type, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters. Liu 2021 https://doi.org/10.1101/2021.03.08.434499 doi:10.1101/2021.03.08.434499 33758836 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). 2021 https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). 2021 https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing NO statistically significant infection rate change amongst the cells, suggesting that furin cleavage typically used for cell entry is not affected by this change one amino acid upstream of the RXXR recognition pattern. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 0.9x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic. Johnson 2020 https://doi.org/10.1101/2020.08.26.268854 doi:10.1101/2020.08.26.268854 32869021 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681R NC_045512.2:g.2042C>G YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). [Inference from similar positively charged substitution P681H actually described in the work] 2021 https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking While the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC). Lubinski 2021 https://doi.org/10.1101/2021.04.06.438731 doi:10.1101/2021.04.06.438731 33851153 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23399,23401,23402,23403 P681R,D614G,D614G,D614G,D614G NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Quantification of the band intensities showed that the P681R mutation, which lies near the proteolytic processing site, caused a small increase in proteolytic processing as measured by a 2-fold decrease in the ratio of S/S2. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23664 A701V NC_045512.2:g.2102C>T YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23664 A701V NC_045512.2:g.2102C>T YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.33 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not in a major wildtype epitope, mutant increases PIWAS epitope score from 0.69% to 2.3% Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain showed a decreased capacity to transduce PK-15 (pig kidney, Sus scrofa) and PaKi (black flying fox kidney, Pteropus alecto) cell line cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed first in a single tiger (cohort of 5), potential adaptation. McAloose 2020 https://doi.org/10.1128/mBio.02220-20 doi:10.1128/mBio.02220-20 33051368 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. T716I was expressed at significantly lower level, accounting for the decreased infectivity of this spike protein. This property may be specific to spike protein biosynthesis in 293T cells and is not likely to reflect the situation in vivo given the reported increase in infectivity of the B.1.1.7 virus. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23897 Q779K NC_045512.2:g.2335C>A YP_009724390.1:p.Gln779Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 20% appearance in 2 passages against Regeneron monoclonal antibody RGN10989 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23948 D796H NC_045512.2:g.2386G>C YP_009724390.1:p.Asp796His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Fatal COVID-19 complications in immunocomprimised patient after immune escape from convalescent plasma Kemp 2020 https://doi.org/10.1101/2020.12.05.20241927 doi:10.1101/2020.12.05.20241927 33398302 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24000 S813I NC_045512.2:g.2438G>T YP_009724390.1:p.Ser813Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2:g.2492C>T YP_009724390.1:p.Ala831Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to neutralizing mAb B38 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2:g.2492C>T YP_009724390.1:p.Ala831Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2:g.2492C>T YP_009724390.1:p.Ala831Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24077 D839N NC_045512.2:g.2515G>A YP_009724390.1:p.Asp839Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry. Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24077 D839Y NC_045512.2:g.2515G>T YP_009724390.1:p.Asp839Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry. Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24130 N856K NC_045512.2:g.2568C>A YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. Lucaci 2021 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24170 I870V NC_045512.2:g.2608A>G YP_009724390.1:p.Ile870Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Appeared at same time as T478K,S494P but listed separately due to distance and different domains affected in the Spike (i.e. putatively an independent mutation from a functional standpoint since the former are from S1, the latter from S2). Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 33176080 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24377,24378 S939F,S939F NC_045512.2:g.2816C>T,NC_045512.2:g.2816C>T YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The neutralizing activity of 6/20 convalescent sera was significantly lower against this single variant pseudotyped virus model, showing similar patterns to the pseudotyped virus model of B.1.1.7. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (70%) increase in infection rate amongst the cells, hence this individual variant is likely to significantly contribute to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24642 T1027I NC_045512.2:g.3080C>T YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 1.51 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Mutation is predicted to lose the T cell epitope for people carrying DRB1*0301 and DRB1*0401, but not for example in those who are DRB1*0701 or DRB1*1501 who would be predicted to show an enhanced response. This is also observed in a study of 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25046 P1162S NC_045512.2:g.3484C>T YP_009724390.1:p.Pro1162Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25249,25249,25249 M1229I,M1229I,M1229I NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25350 P1263L NC_045512.2:g.3788C>T YP_009724390.1:p.Pro1263Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant in the cytoplasmic tail, shown in vitro to increase Spike subunit fusion required for cell entry Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25855 D155Y NC_045512.2:g.463G>T YP_009724391.1:p.Asp155Tyr open reading frame 3a gene (SARS-CoV-2) orf3a gene (SARS-CoV-2) open reading frame 3a protein (SARS-CoV-2) Orf3a protein (SARS-CoV-2) caveolin binding In silico, this mutation is the only one weakening ORF3a's binding affinity for caveolin-1 (essential for entry and endomembrane trafficking of SARS-CoV-2). This mutation is a widespread homoplasy in 20A and 20B lineages. Gupta 2021 https://doi.org/10.1101/2021.03.26.437194 doi:10.1101/2021.03.26.437194 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26029 Q213K NC_045512.2:g.637C>A YP_009724391.1:p.Gln213Lys open reading frame 3a gene (SARS-CoV-2) orf3a gene (SARS-CoV-2) open reading frame 3a protein (SARS-CoV-2) Orf3a protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*01:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26029 Q213K NC_045512.2:g.637C>A YP_009724391.1:p.Gln213Lys open reading frame 3a gene (SARS-CoV-2) orf3a gene (SARS-CoV-2) open reading frame 3a protein (SARS-CoV-2) Orf3a protein (SARS-CoV-2) T cell evasion "Variant causes complete loss of T cell line responsiveness to A*01:01-restricted CD8+ ORF3a epitope, which is otherwise ""consistently dominant and of high magnitude""." de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26256 F4F NC_045512.2:g.12C>T YP_009724392.1:p.Phe4Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26268,26269,26270 T9I,T9I,T9I NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~300 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26268,26269,26270 T9I,T9I,T9I NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26296 L18I NC_045512.2:g.52C>A YP_009724392.1:p.Leu18Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (47x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26299 L19F NC_045512.2:g.55C>T YP_009724392.1:p.Leu19Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26312 F23C NC_045512.2:g.68T>G YP_009724392.1:p.Phe23Cys envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~8.8 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26314 V24M NC_045512.2:g.70G>A YP_009724392.1:p.Val24Met envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26319 V25V NC_045512.2:g.75A>G YP_009724392.1:p.Val25Val envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (45x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26333 T30I NC_045512.2:g.89C>T YP_009724392.1:p.Thr30Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26353 L37F NC_045512.2:g.109C>T YP_009724392.1:p.Leu37Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26395 L51I NC_045512.2:g.151C>A YP_009724392.1:p.Leu51Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (47x overrepresentation vs expected count of ~24 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26416 V58L NC_045512.2:g.172G>C YP_009724392.1:p.Val58Leu envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26428 V62F NC_045512.2:g.184G>T YP_009724392.1:p.Val62Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (18x overrepresentation vs expected count of ~333 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26442 N66K NC_045512.2:g.198T>G YP_009724392.1:p.Asn66Lys envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~23 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26447 S68F NC_045512.2:g.203C>T YP_009724392.1:p.Ser68Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26447 S68C NC_045512.2:g.203C>G YP_009724392.1:p.Ser68Cys envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (58x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26456 P71R NC_045512.2:g.212C>G YP_009724392.1:p.Pro71Arg envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26467 V75L NC_045512.2:g.223G>C YP_009724392.1:p.Val75Leu envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (3762.7x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526 A2S NC_045512.2:g.4G>T YP_009724393.1:p.Ala2Ser membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) immunosuppression variant emergence Emergent as 16% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing. Avanzato 2020 https://doi.org/10.1016/j.cell.2020.10.049 doi:10.1016/j.cell.2020.10.049 33248470 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526 A2S NC_045512.2:g.4G>T YP_009724393.1:p.Ala2Ser membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (38x overrepresentation vs expected count of ~334 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526,26527,26529 D3H,D3H,D3H NC_045512.2:g.7G>C,NC_045512.2:g.7G>C,NC_045512.2:g.7G>C YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (227x overrepresentation vs expected count of ~14 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26528,26528,26528 A2A,A2A,A2A NC_045512.2:g.6A>T,NC_045512.2:g.6A>G,NC_045512.2:g.6A>C YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (25x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26530 D3G NC_045512.2:g.8A>G YP_009724393.1:p.Asp3Gly membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (31x overrepresentation vs expected count of ~53 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26542 T7I NC_045512.2:g.20C>T YP_009724393.1:p.Thr7Ile membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26546 I8I NC_045512.2:g.24T>C YP_009724393.1:p.Ile8Ile membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~80 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26573,26576,26577 Q19E,Q19E,Q19E NC_045512.2:g.55C>G,NC_045512.2:g.55C>G,NC_045512.2:g.55C>G YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~8 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26620 C33S NC_045512.2:g.98G>C YP_009724393.1:p.Cys33Ser membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~32 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26645 N41N NC_045512.2:g.123C>T YP_009724393.1:p.Asn41Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (19x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26681 F53F NC_045512.2:g.159C>T YP_009724393.1:p.Phe53Phe membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (163x overrepresentation vs expected count of ~567 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26730 V70L NC_045512.2:g.208G>C YP_009724393.1:p.Val70Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26748 I76V NC_045512.2:g.226A>G YP_009724393.1:p.Ile76Val membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26748 I76L NC_045512.2:g.226A>C YP_009724393.1:p.Ile76Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~9 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26749 I76T NC_045512.2:g.227T>C YP_009724393.1:p.Ile76Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (19x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26767 I82T NC_045512.2:g.245T>C YP_009724393.1:p.Ile82Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) homoplasy This mutation presents mainly within the B.1 (44.0%) and B.1.525 (38.1%) lineages. Currently, 99.7% of the B.1.525 lineage isolates carry the M:I82T mutation. While this mutation is scattered across multiple phylogenetic clades, most cases cluster in two recent clades, suggesting a likely selective advantage in certain haplotype backgrounds. Shen 2021 https://doi.org/10.1080/22221751.2021.1922097 doi:10.1080/22221751.2021.1922097 33896413 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26767 I82T NC_045512.2:g.245T>C YP_009724393.1:p.Ile82Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (67x overrepresentation vs expected count of ~42 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26801,26801,26801 L93L,L93L,L93L NC_045512.2:g.279C>G,NC_045512.2:g.279C>A,NC_045512.2:g.279C>T YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~628 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26855,26858 F112F,F112F NC_045512.2:g.336C>T,NC_045512.2:g.336C>T YP_009724393.1:p.Phe112Phe,YP_009724393.1:p.Phe112Phe membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~463 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26861 N113N NC_045512.2:g.339T>C YP_009724393.1:p.Asn113Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (57x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26873 N117N NC_045512.2:g.351C>T YP_009724393.1:p.Asn117Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26882,26882 L120L,L120L NC_045512.2:g.360C>A,NC_045512.2:g.360C>T YP_009724393.1:p.Leu120Leu,YP_009724393.1:p.Leu120Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26894,26894 L124L,L124L NC_045512.2:g.372C>T,NC_045512.2:g.372C>G YP_009724393.1:p.Leu124Leu,YP_009724393.1:p.Leu124Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26895 H125Y NC_045512.2:g.373C>T YP_009724393.1:p.His125Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (22x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26895 H125Y NC_045512.2:g.373C>T YP_009724393.1:p.His125Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) homoplasy In experimental models of SARA_CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26907,26909,26909 L129L,L129L,L129L NC_045512.2:g.385C>T,NC_045512.2:g.387G>A,NC_045512.2:g.387G>T YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26927 E135E NC_045512.2:g.405A>G YP_009724393.1:p.Glu135Glu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (232x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26951,26951,26951 V143V,V143V,V143V NC_045512.2:g.429G>C,NC_045512.2:g.429G>A,NC_045512.2:g.429G>T YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~508 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26966 H148H NC_045512.2:g.444T>C YP_009724393.1:p.His148His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26972 R150R NC_045512.2:g.450T>C YP_009724393.1:p.Arg150Arg membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~89 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26985 H155N NC_045512.2:g.463C>A YP_009724393.1:p.His155Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26987 H155H NC_045512.2:g.465T>C YP_009724393.1:p.His155His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27021 E167Q NC_045512.2:g.499G>C YP_009724393.1:p.Glu167Gln membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27035,27038 T172T,T172T NC_045512.2:g.516A>G,NC_045512.2:g.516A>G YP_009724393.1:p.Thr172Thr,YP_009724393.1:p.Thr172Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27059 Y179Y NC_045512.2:g.537C>T YP_009724393.1:p.Tyr179Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27112 S197T NC_045512.2:g.590G>C YP_009724393.1:p.Ser197Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (18x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27134 Y204Y NC_045512.2:g.612T>C YP_009724393.1:p.Tyr204Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27143 N207N NC_045512.2:g.621C>T YP_009724393.1:p.Asn207Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27147 D209H NC_045512.2:g.625G>C YP_009724393.1:p.Asp209His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (81x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27367 Q56X NC_045512.2:g.166C>T YP_009724394.1:p.Gln56Xaa open reading frame 6 gene (SARS-CoV-2) orf6 gene (SARS-CoV-2) open reading frame 6 protein (SARS-CoV-2) Orf6 protein (SARS-CoV-2) IFN activity The residues listed are determinants of the potent IFN-antagonistic activity of SARS-CoV-2 ORF6 (via blocking mRNA nuclear export) Kimura 2020 https://doi.org/10.2139/ssrn.3690468 doi:10.2139/ssrn.3690468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28144 L84S NC_045512.2:g.251T>C YP_009724396.1:p.Leu84Ser open reading frame 8 gene (SARS-CoV-2) orf8 gene (SARS-CoV-2) open reading frame 8 protein (SARS-CoV-2) Orf8 protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28307,28309,28310,28311 P13L,P13L,P13L,P13L NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28307,28309,28310,28311 P13L,P13L,P13L,P13L NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13). de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28310 P13S NC_045512.2:g.37C>T YP_009724397.2:p.Pro13Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13). de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28310 P13S NC_045512.2:g.37C>T YP_009724397.2:p.Pro13Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*27:05. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28769 T166A NC_045512.2:g.496A>G YP_009724397.2:p.Thr166Ala nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) variant linear antibody epitope effects Confers a significant PIWAS value decrease (reduced antigenicity) Haynes 2020 https://doi.org/10.1101/2020.11.23.20235002 doi:10.1101/2020.11.23.20235002 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28853 S194T NC_045512.2:g.580T>A YP_009724397.2:p.Ser194Thr nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28854 S194L NC_045512.2:g.581C>T YP_009724397.2:p.Ser194Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) homoplasy Mutation with a population frequency of 30% in a Mexican dataset, primarily of lineage 20B, but also present in a substantial number of 20A lineage sequences, suggesting convergent evolution. Barona-Gomez 2021 https://doi.org/10.1101/2021.05.18.21256128 doi:10.1101/2021.05.18.21256128 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28854 S194L NC_045512.2:g.581C>T YP_009724397.2:p.Ser194Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) outcome hazard ratio In March 2021 this variant had an allele frequency of 47.62 and 7.25% in deceased patients, compared to 35.16 and 3.20% of the same variant in recovered patients, from the Gujarat and global datasets. Joshi 2021 https://doi.org/10.3389/fgene.2021.586569 doi:10.3389/fgene.2021.586569 33815459 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28869 P199L NC_045512.2:g.596C>T YP_009724397.2:p.Pro199Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021 https://doi.org/10.1101/2021.08.05.455082 doi:10.1101/2021.08.05.455082 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28879 S202R NC_045512.2:g.606T>G YP_009724397.2:p.Ser202Arg nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows major increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021 https://doi.org/10.1101/2021.08.05.455082 doi:10.1101/2021.08.05.455082 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28881 R203M NC_045512.2:g.608G>T YP_009724397.2:p.Arg203Met nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows most increase in RNA content of any N mutation tested, suggesting that this mutation improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021 https://doi.org/10.1101/2021.08.05.455082 doi:10.1101/2021.08.05.455082 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28977 S235F NC_045512.2:g.704C>T YP_009724397.2:p.Ser235Phe nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) variant linear antibody epitope effects Substantially increases epitope and antigen scores in 2 of 579 individuals (should increase immune response). In the B1.1.7 lineage this is largely counteracted by the D3L mutation, which decreases PIWAS signal significantly in 1.5% of COVID patients, for a net neutral effect at the population level. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29239,29239 M322I,M322I NC_045512.2:g.966G>A,NC_045512.2:g.966G>T YP_009724397.2:p.Met322Ile,YP_009724397.2:p.Met322Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. Agerer 2021 https://doi.org/10.1126/sciimmunol.abg6461 doi:10.1126/sciimmunol.abg6461 33664060 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29247 T325I NC_045512.2:g.974C>T YP_009724397.2:p.Thr325Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes partial loss of T cell line responsiveness and CTL killing ability by B*40:01-restricted CD8+ N epitope MEVTPSGTWL 322-331. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29247 T325I NC_045512.2:g.974C>T YP_009724397.2:p.Thr325Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29266,29266 L331F,L331F NC_045512.2:g.993G>T,NC_045512.2:g.993G>C YP_009724397.2:p.Leu331Phe,YP_009724397.2:p.Leu331Phe nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. Agerer 2021 https://doi.org/10.1126/sciimmunol.abg6461 doi:10.1126/sciimmunol.abg6461 33664060 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29409 T379I NC_045512.2:g.1136C>T YP_009724397.2:p.Thr379Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 335 R24C NC_045512.2:g.70C>T YP_009724389.1:p.Arg24Cys YP_009724389.1:Arg24Cys open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (25x overrepresentation vs expected count of 514 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 347 V28I NC_045512.2:g.82G>A YP_009724389.1:p.Val28Ile YP_009724389.1:Val28Ile open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (30x overrepresentation vs expected count of 143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 383 S40P NC_045512.2:g.118T>C YP_009724389.1:p.Ser40Pro YP_009724389.1:Ser40Pro open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~58 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 396 Q44L NC_045512.2:g.131A>T YP_009724389.1:p.Gln44Leu YP_009724389.1:Gln44Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~19 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 443 V60I NC_045512.2:g.178G>A YP_009724389.1:p.Val60Ile YP_009724389.1:Val60Ile open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 489 D75G NC_045512.2:g.224A>G YP_009724389.1:p.Asp75Gly YP_009724389.1:Asp75Gly open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 490,490 D75E,D75E NC_045512.2:g.225T>G,NC_045512.2:g.225T>A YP_009724389.1:p.Asp75Glu,YP_009724389.1:p.Asp75Glu YP_009724389.1:Asp75Glu,YP_009724389.1:Asp75Glu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~20 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) immunosuppression variant emergence Emergent as 22% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing. Avanzato 2020 https://doi.org/10.1016/j.cell.2020.10.049 doi:10.1016/j.cell.2020.10.049 33248470 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) IFN activity Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-517) was tested in vitro for IFN response. Lin 2021 https://doi.org/10.1016/j.chom.2021.01.015 doi:10.1016/j.chom.2021.01.015 33548198 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) IFN activity Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-523) was tested in vitro for IFN response. Lin 2021 https://doi.org/10.1016/j.chom.2021.01.015 doi:10.1016/j.chom.2021.01.015 33548198 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) IFN activity Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 500-523) was tested in vitro for IFN response. Lin 2021 https://doi.org/10.1016/j.chom.2021.01.015 doi:10.1016/j.chom.2021.01.015 33548198 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,509,518 M85V,M85V,M85V NC_045512.2:g.253A>G,NC_045512.2:g.253A>G,NC_045512.2:g.253A>G YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val YP_009724389.1:Met85Val,YP_009724389.1:Met85Val,YP_009724389.1:Met85Val open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 508 H81Q NC_045512.2:g.243T>A YP_009724389.1:p.His81Gln YP_009724389.1:His81Gln open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (30x overrepresentation vs expected count of ~20 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 510 M85K NC_045512.2:g.254T>A YP_009724389.1:p.Met85Lys YP_009724389.1:Met85Lys open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~12 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 561 R99H NC_045512.2:g.296G>A YP_009724389.1:p.Arg99His YP_009724389.1:Arg99His open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 563 S100C NC_045512.2:g.298A>T YP_009724389.1:p.Ser100Cys YP_009724389.1:Ser100Cys open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (33x overrepresentation vs expected count of ~19 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 593 H110Y NC_045512.2:g.328C>T YP_009724389.1:p.His110Tyr YP_009724389.1:His110Tyr open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (22x overrepresentation vs expected count of ~514 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 593 H110D NC_045512.2:g.328C>G YP_009724389.1:p.His110Asp YP_009724389.1:His110Asp open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~11 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 606 I114T NC_045512.2:g.341T>C YP_009724389.1:p.Ile114Thr YP_009724389.1:Ile114Thr open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (155x overrepresentation vs expected count of ~58 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 657 A131V NC_045512.2:g.392C>T YP_009724389.1:p.Ala131Val YP_009724389.1:Ala131Val open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~514 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 677 A138T NC_045512.2:g.412G>A YP_009724389.1:p.Ala138Thr YP_009724389.1:Ala138Thr open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 761 S166G NC_045512.2:g.496A>G YP_009724389.1:p.Ser166Gly YP_009724389.1:Ser166Gly open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (132x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 798 N178S NC_045512.2:g.533A>G YP_009724389.1:p.Asn178Ser YP_009724389.1:Asn178Ser open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay From d68960917e343a66c8ee0a6b0ecb84dc9cad238b Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 17:08:37 -0700 Subject: [PATCH 070/161] match new DH format --- bin/addpmids2functionalannotation.py | 5 +++++ 1 file changed, 5 insertions(+) diff --git a/bin/addpmids2functionalannotation.py b/bin/addpmids2functionalannotation.py index 31ef7d9c..70cd216b 100755 --- a/bin/addpmids2functionalannotation.py +++ b/bin/addpmids2functionalannotation.py @@ -38,6 +38,7 @@ def parse_args(): pmids_df = pmids_df[pmids_df["PMID"].notna()] pmids_df = pmids_df.drop_duplicates(subset='DOI', keep='first') pmids_df = pmids_df[['PMID', 'DOI']] + pmids_df['DOI'] = "doi:" + pmids_df['DOI'] #merge them functional_annotation_df = functional_annotation_df.drop(columns='PMID') @@ -47,5 +48,9 @@ def parse_args(): # rearrange columns functional_annotation_df = functional_annotation_df[functional_annotation_columns] + # make sure years are integers + #functional_annotation_df['publication year'] = functional_annotation_df['publication year'].astype(str).replace('.0', 'CAT', regex=False) + functional_annotation_df["publication year"] = functional_annotation_df["publication year"].astype('Int64') + # save to TSV functional_annotation_df.to_csv(args.outputfile, sep='\t', header=True, index=False) \ No newline at end of file From 8e68d0c3fc03bd03f25e4bd08111640ceae9b649 Mon Sep 17 00:00:00 2001 From: Madeline Iseminger <32916719+miseminger@users.noreply.github.com> Date: Thu, 24 Oct 2024 17:11:58 -0700 Subject: [PATCH 071/161] Delete assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v1.0.tsv --- ...kay_functionalAnnotation_SARSCoV2_v1.0.tsv | 1976 ----------------- 1 file changed, 1976 deletions(-) delete mode 100644 assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v1.0.tsv diff --git a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v1.0.tsv b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v1.0.tsv deleted file mode 100644 index 622e8ef3..00000000 --- a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v1.0.tsv +++ /dev/null @@ -1,1976 +0,0 @@ -organism reference accession reference database name nucleotide position original mutation description nucleotide mutation amino acid mutation amino acid mutation alias gene name gene symbol protein name protein symbol assay mutation functional effect category mutation functional effect description author publication year URL DOI PMID peer review status curator mutation functional annotation resource -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S aerosolization Alpha variant cases in a large campus study showed fine-aerosol shedding amongst unmasked participants remained significantly greater for alpha variant infections (18-fold, 95% CI, 3.4 to 92-fold) after adjusting for the increased viral RNA in MTS and saliva, the number of coughs during sampling sessions, and symptom. After controlling for the effect of masks and numbers of coughs during sampling, alpha variant infection was associated with a 100-fold (95% CI, 16 to 650-fold) increase in coarse- and a 73-fold (95% CI, 15 to 350-fold) increase in fine-aerosol RNA shedding. Adenaiye 2021.0 https://doi.org/10.1093/cid/ciab797 10.1093/cid/ciab797 34519774 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,23399,23401,23401,23402,23403,23403 E156_R158delinsG,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.467_472del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,, S S surface glycoprotein S syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28307,28308,28309,28309,28310,28310,28311,28311 P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L NC_045512.2:g.38C>T,,,NC_045512.2:g.38C>T,,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T, YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu ,,,,,,, N N nucleocapsid phosphoprotein N homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021.0 https://doi.org/10.1101/2021.05.19.444774 10.1101/2021.05.19.444774 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29409 T379I NC_045512.2:g.1136C>T YP_009724397.2:p.Thr379Ile N N nucleocapsid phosphoprotein N homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021.0 https://doi.org/10.1101/2021.05.19.444774 10.1101/2021.05.19.444774 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S homoplasy Variant within the six key residues in the receptor binding domain (RBD). Independently reported in UK, Australia (same origin as UK), and South Africa (independent origin). Flores-Alanis 2021.0 https://doi.org/10.3390/pathogens10020184 10.3390/pathogens10020184 33572190 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21759 H66R NC_045512.2:g.197A>G YP_009724390.1:p.His66Arg S S surface glycoprotein S homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent, especially on a D614 wildtype background. Borges 2021.0 https://doi.org/10.1101/2021.05.19.444774 10.1101/2021.05.19.444774 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly S S surface glycoprotein S homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent. Borges 2021.0 https://doi.org/10.1101/2021.05.19.444774 10.1101/2021.05.19.444774 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23521,23522,23524,23524,23525 H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,, S S surface glycoprotein S homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent. Borges 2021.0 https://doi.org/10.1101/2021.05.19.444774 10.1101/2021.05.19.444774 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26542 T7I NC_045512.2:g.20C>T YP_009724393.1:p.Thr7Ile M M membrane glycoprotein M anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021.0 https://doi.org/10.1101/2021.01.19.21249592 10.1101/2021.01.19.21249592 33501468 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26319 V25V NC_045512.2:g.75A>G YP_009724392.1:p.Val25Val E E envelope protein E frequency based fitness Calculated to have an increased fitness (45x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26466,26467 V75L,V75L ,NC_045512.2:g.223G>C YP_009724392.1:p.Val75Leu,YP_009724392.1:p.Val75Leu , E E envelope protein E frequency based fitness Calculated to have an increased fitness (3762.7x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26416 V58L NC_045512.2:g.172G>C YP_009724392.1:p.Val58Leu E E envelope protein E frequency based fitness Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26428 V62F NC_045512.2:g.184G>T YP_009724392.1:p.Val62Phe E E envelope protein E frequency based fitness Calculated to have an increased fitness (18x overrepresentation vs expected count of ~333 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26268,26268,26269,26270 T9I,T9I,T9I,T9I NC_045512.2:g.26C>T,,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile ,,, E E envelope protein E frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~300 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26447 S68C NC_045512.2:g.203C>G YP_009724392.1:p.Ser68Cys E E envelope protein E frequency based fitness Calculated to have an increased fitness (58x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26456 P71R NC_045512.2:g.212C>G YP_009724392.1:p.Pro71Arg E E envelope protein E frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26442 N66K NC_045512.2:g.198T>G YP_009724392.1:p.Asn66Lys E E envelope protein E frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~23 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26295,26296 L18I,L18I ,NC_045512.2:g.52C>A YP_009724392.1:p.Leu18Ile,YP_009724392.1:p.Leu18Ile , E E envelope protein E frequency based fitness Calculated to have an increased fitness (47x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26256 F4F NC_045512.2:g.12C>T YP_009724392.1:p.Phe4Phe E E envelope protein E frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26312 F23C NC_045512.2:g.68T>G YP_009724392.1:p.Phe23Cys E E envelope protein E frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~8.8 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28877 G204R YP_009724397.2:p.Gly204Arg N N nucleocapsid phosphoprotein N posttranslational modifications This variant, caused by three consecutive SNPs, consistently shows a neighbouring serine 206 (S206) site is highly phosphorylated in the mutant N protein via mass spectrometry. Mourier 2021.0 https://doi.org/10.1101/2021.05.06.21256706 10.1101/2021.05.06.21256706 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21974,23224,23399,23401,23401,23402,23403,23403 D138H,E554D,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.412G>C,NC_045512.2:g.1662G>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp138His,YP_009724390.1:p.Glu554Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,, S S surface glycoprotein S immunosuppression variant emergence Studying 94 COVID-19 extended infection cases with genomics April 1 to October 17, 2020, one case developed 23 mutations in a 19 day period, including this combination in Spike. Landis 2021.0 https://doi.org/10.1101/2021.05.08.21256775 10.1101/2021.05.08.21256775 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S immunosuppression variant emergence Dominant (70%) in day 21 of prolonged infection in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then nearly disappearing (<5%) by day 27. Chen 2021.0 https://doi.org/10.1101/2021.04.08.21254791 10.1101/2021.04.08.21254791 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S immunosuppression variant emergence Individual variants appearing at <=30% frequency at day 21 in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then appearing all at >95% frequency at day 27. Chen 2021.0 https://doi.org/10.1101/2021.04.08.21254791 10.1101/2021.04.08.21254791 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S immunosuppression variant emergence "The so-called ""delta F"" variant combination previously observed in mink spillover events also emerged in a lymphoma patient (non-Hodgkin diffuse B-cell lymphoma IV stage B) with a long-term COVID-19 infection (4 months) where 18 de novo mutation occureed overall. Patient was taking rituximab, the B-cell-depleting agent, and had no detectable neutralizing antibody response." Bazykin 2021.0 https://virological.org/t/emergence-of-y453f-and-69-70hv-mutations-in-a-lymphoma-patient-with-long-term-covid-19/580 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22111 Q183H NC_045512.2:g.549G>T YP_009724390.1:p.Gln183His S S surface glycoprotein S immunosuppression variant emergence Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Choi 2020.0 https://doi.org/10.1056/NEJMc2031364 10.1056/NEJMc2031364 33176080 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S immunosuppression variant emergence Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Choi 2020.0 https://doi.org/10.1056/NEJMc2031364 10.1056/NEJMc2031364 33176080 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,22995,23042 T478K,T478K,S494P NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1480T>C YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser494Pro ,, S S surface glycoprotein S immunosuppression variant emergence Combination of RBD mutations appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome complicated by diffuse alveolar hemorrhage, who was receiving anticoagulation therapy, glucocorticoids, cyclophosphamide, and intermittent rituximab and eculizumab. Choi 2020.0 https://doi.org/10.1056/NEJMc2031364 10.1056/NEJMc2031364 33176080 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24170 I870V NC_045512.2:g.2608A>G YP_009724390.1:p.Ile870Val S S surface glycoprotein S immunosuppression variant emergence Appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Appeared at same time as T478K,S494P but listed separately due to distance and different domains affected in the Spike (i.e. putatively an independent mutation from a functional standpoint since the former are from S1, the latter from S2). Choi 2020.0 https://doi.org/10.1056/NEJMc2031364 10.1056/NEJMc2031364 33176080 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His S S surface glycoprotein S immunosuppression variant emergence Based on structural modelling, this change detected on day 128 sequencing in a chronically infected patient would alter an extensive network of polar interactions with antibody residue R94VH, a germline antibody residue that is conserved in all of the potent VH3-53/3-66-derived antibodies isolated from a convalescent donor 5 weeks after infection. Clark 2021.0 https://doi.org/10.1016/j.cell.2021.03.027 10.1016/j.cell.2021.03.027 33831372 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444R NC_045512.2:g.1331A>G YP_009724390.1:p.Lys444Arg S S surface glycoprotein S monoclonal antibody serial passage escape Identified in 6/20 replicates of recombinant VSV growth in the presence of mAb COV2-2130. Dong 2021.0 https://doi.org/10.1101/2021.01.27.428529 10.1101/2021.01.27.428529 33532768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346I,R346I NC_045512.2:g.1037G>T,NC_045512.2:g.1037G>T YP_009724390.1:p.Arg346Ile,YP_009724390.1:p.Arg346Ile , S S surface glycoprotein S monoclonal antibody serial passage escape Provides ~80% escape from mAb COV2-2130, even though its appearance in culture is formed without selective mAb pressure. Dong 2021.0 https://doi.org/10.1101/2021.01.27.428529 10.1101/2021.01.27.428529 33532768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,22597,22597,22599 E484K,E484K,R346K,R346K,R346K ,NC_045512.2:g.1450G>A,,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys ,,,, S S surface glycoprotein S monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E484K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K NC_045512.2:g.1380T>A,,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22941 N460I NC_045512.2:g.1379A>T YP_009724390.1:p.Asn460Ile S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26268,26268,26269,26270 T9I,T9I,T9I,T9I NC_045512.2:g.26C>T,,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile ,,, E E envelope protein E homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021.0 https://doi.org/10.1101/2021.05.19.444774 10.1101/2021.05.19.444774 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460H NC_045512.2:g.1378A>C YP_009724390.1:p.Asn460His S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460H NC_045512.2:g.1378A>C YP_009724390.1:p.Asn460His S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460H NC_045512.2:g.1378A>C YP_009724390.1:p.Asn460His S S surface glycoprotein S monoclonal antibody serial passage escape Mild escape mutant emergent for class 1 antibody C613 in vitro. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22941 N460S NC_045512.2:g.1379A>G YP_009724390.1:p.Asn460Ser S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26299 L19F NC_045512.2:g.55C>T YP_009724392.1:p.Leu19Phe E E envelope protein E homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021.0 https://doi.org/10.1101/2021.05.19.444774 10.1101/2021.05.19.444774 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460Y NC_045512.2:g.1378A>T YP_009724390.1:p.Asn460Tyr S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22928 F456V NC_045512.2:g.1366T>G YP_009724390.1:p.Phe456Val S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26314 V24M NC_045512.2:g.70G>A YP_009724392.1:p.Val24Met E E envelope protein E homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021.0 https://doi.org/10.1101/2021.05.19.444774 10.1101/2021.05.19.444774 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22928 F456V NC_045512.2:g.1366T>G YP_009724390.1:p.Phe456Val S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22928 F456V NC_045512.2:g.1366T>G YP_009724390.1:p.Phe456Val S S surface glycoprotein S monoclonal antibody serial passage escape Moderate in vitro selection against class 1 (Spike 'up' conformation) antibodies C683 and C664. Unclassified antibody C666 selected for the emergence of the F456V mutation in vitro. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26333 T30I NC_045512.2:g.89C>T YP_009724392.1:p.Thr30Ile E E envelope protein E homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021.0 https://doi.org/10.1101/2021.05.19.444774 10.1101/2021.05.19.444774 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,, S S surface glycoprotein S syncytium formation ~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26353 L37F NC_045512.2:g.109C>T YP_009724392.1:p.Leu37Phe E E envelope protein E homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021.0 https://doi.org/10.1101/2021.05.19.444774 10.1101/2021.05.19.444774 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26447 S68F NC_045512.2:g.203C>T YP_009724392.1:p.Ser68Phe E E envelope protein E homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021.0 https://doi.org/10.1101/2021.05.19.444774 10.1101/2021.05.19.444774 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21587 P9S NC_045512.2:g.25C>T YP_009724390.1:p.Pro9Ser S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2M28, S2X28 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21606 C15F NC_045512.2:g.44G>T YP_009724390.1:p.Cys15Phe S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond. McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21605 C15R NC_045512.2:g.43T>C YP_009724390.1:p.Cys15Arg S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond. McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800 D80N NC_045512.2:g.238G>A YP_009724390.1:p.Asp80Asn S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21969 C136Y NC_045512.2:g.407G>A YP_009724390.1:p.Cys136Tyr S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X333 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21977 P139S NC_045512.2:g.415C>T YP_009724390.1:p.Pro139Ser S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21929 A123S NC_045512.2:g.367G>T YP_009724390.1:p.Ala123Ser S S surface glycoprotein S monoclonal antibody serial passage escape Selected in passage with mAb COV2-2489 during alanine mutagenesis antibody mapping experiment. Suryadevara 2021.0 https://doi.org/10.1101/2021.01.19.427324 10.1101/2021.01.19.427324 33501445 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22036 R158S NC_045512.2:g.474A>T YP_009724390.1:p.Arg158Ser S S surface glycoprotein S monoclonal antibody serial passage escape Selected three times in passage with mAb COV2-2489. Suryadevara 2021.0 https://doi.org/10.1101/2021.01.19.427324 10.1101/2021.01.19.427324 33501445 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp ,,,,,,,,,,,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp ,,,,,,,,,,,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp ,,,,,,,,,,,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Selected twice in passage with mAb COV2-2489. Suryadevara 2021.0 https://doi.org/10.1101/2021.01.19.427324 10.1101/2021.01.19.427324 33501445 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28854 S194L NC_045512.2:g.581C>T YP_009724397.2:p.Ser194Leu N N nucleocapsid phosphoprotein N outcome hazard ratio In March 2021 this variant had an allele frequency of 47.62 and 7.25% in deceased patients, compared to 35.16 and 3.20% of the same variant in recovered patients, from the Gujarat and global datasets. Joshi 2021.0 https://doi.org/10.3389/fgene.2021.586569 10.3389/fgene.2021.586569 33815459 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22001 K147Q NC_045512.2:g.439A>C YP_009724390.1:p.Lys147Gln S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22002 K147T NC_045512.2:g.440A>C YP_009724390.1:p.Lys147Thr S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X333 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21997,21997,21999,22000,22000,22001 K147E,K147E,K147E,K147E,K147E,K147E NC_045512.2:g.439A>G,,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,,NC_045512.2:g.439A>G YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2X28, S2X333 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034 R158G NC_045512.2:g.472A>G YP_009724390.1:p.Arg158Gly S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22293 L244S NC_045512.2:g.731T>C YP_009724390.1:p.Leu244Ser S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22301 S247R NC_045512.2:g.739A>C YP_009724390.1:p.Ser247Arg S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,23399,23401,23401,23402,23403,23403,23944,23944,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22894,22896,22898,23048,23521,23521,23522,23524,23524,23525,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,24130,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22673,22679,22679,22686,22992,21846,22992,22995,23202,21987,21990,23071,23071,23074,23074,23075,23075 A67V,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G446S,G446S,G446S,G496S,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N856K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,S371L,S373P,S373P,S375F,S477N,T95I,T478K,T478K,T547K,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H NC_045512.2:g.200C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2568C>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1640C>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 28.7x-fold lower (95% CI: 0.03x-0.05) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022.0 https://doi.org/10.1101/2022.06.05.494889 10.1101/2022.06.05.494889 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22314 P251L NC_045512.2:g.752C>T YP_009724390.1:p.Pro251Leu S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317 G252D NC_045512.2:g.755G>A YP_009724390.1:p.Gly252Asp S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317,22319,22320 D253G,D253G,D253G NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly ,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22326 S255F NC_045512.2:g.764C>T YP_009724390.1:p.Ser255Phe S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22328,22329,22331 G257S,G257S,G257S NC_045512.2:g.769G>A,NC_045512.2:g.769G>A,NC_045512.2:g.769G>A YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser ,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334 W258R NC_045512.2:g.772T>C YP_009724390.1:p.Trp258Arg S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21641,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22784,22785,22786,22786,22671,22672,22672,22673,22674,22679,22679,22686,22992,21594,21603,21603,21614,21617,21617,21618,21618,22992,22995,22194,22197,22198,22198,22199,22200,23071,23071,23074,23074,23075,23075 A27S,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,R408S,R408S,R408S,R408S,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T478K,T478K,V213G,V213G,V213G,V213G,V213G,V213G,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H NC_045512.2:g.79G>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 3.9x-fold lower (95% CI: 0.14x-0.17x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022.0 https://doi.org/10.1101/2022.06.05.494889 10.1101/2022.06.05.494889 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21641,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,22811,22812,22813,22813,22813,22917,22879,22879,22881,22882,22882,22882,23060,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22784,22785,22786,22786,22671,22672,22672,22673,22674,22679,22679,22686,22992,23673,21594,21603,21603,21614,21617,21617,21618,21618,22992,22995,22194,22197,22198,22198,22199,22200,23071,23071,23074,23074,23075,23075 A27S,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,R408S,R408S,R408S,R408S,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,S704L,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T478K,T478K,V213G,V213G,V213G,V213G,V213G,V213G,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H NC_045512.2:g.79G>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.2111C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Ser704Leu,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 3.9x-fold lower (95% CI: 0.14x-0.18x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022.0 https://doi.org/10.1101/2022.06.05.494889 10.1101/2022.06.05.494889 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22679,22679 S373P,S373P NC_045512.2:g.1117T>C, YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro , S S surface glycoprotein S monoclonal antibody serial passage escape Reduce affinity for mildly cross-reactive CR3022 (2003 pandemic SARS monoclonal antibody cross-reactive to SARS-CoV-2) Long 2020.0 https://doi.org/10.1128/mBio.02707-20 10.1128/mBio.02707-20 33127862 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22894,22896,22898,23521,23521,23522,23524,23524,23525,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22671,22672,22672,22673,22674,22679,22679,22686,22992,21846,22992,22995,21987,21990,23071,23071,23074,23074,23075,23075 A67V,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G446S,G446S,G446S,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,T95I,T478K,T478K,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H NC_045512.2:g.200C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 4.2x-fold lower (95% CI: 0.15x-0.20x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022.0 https://doi.org/10.1101/2022.06.05.494889 10.1101/2022.06.05.494889 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811 K417D YP_009724390.1:p.Lys417Asp S S surface glycoprotein S monoclonal antibody serial passage escape Most and moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Mildly effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811 K417D YP_009724390.1:p.Lys417Asp S S surface glycoprotein S monoclonal antibody serial passage escape Most and moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Mildly effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811 K417D YP_009724390.1:p.Lys417Asp S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, but moderate decrease in ACE2 binding affinity Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S syncytium formation ~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22679,22679,24465,24466,24466,24468,24469,23521,23521,23522,23524,23524,23525,22194,22197,22198,22198,22199,22200,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21641,24421,24421,24422,24423,24424,24424,24424,23060,23062,23062,23063,23063,21594,21603,21603,21614,21617,21617,21618,21618,22879,22879,22881,22882,22882,22882,23595,23596,23596,23598,23599,23853,23854,23071,23071,23074,23074,23075,23075,23944,23944,23947,23948,23948,22992,22995,22671,22672,22672,22673,22674,22811,22812,22813,22813,22813,23018,22576,22577,22578,22784,22785,22786,22786,23604,23604,22686,22771,22775,22775,23053,23053,23054,23054,23055,23055,22992,23009,23010,23012,23013,23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 S373P,S373P,N969K,N969K,N969K,N969K,N969K,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,V213G,V213G,V213G,V213G,V213G,V213G,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A27S,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N501Y,N501Y,N501Y,N501Y,N501Y,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,N440K,N440K,N440K,N440K,N440K,N440K,N679K,N679K,N679K,N679K,N679K,N764K,N764K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D796Y,D796Y,D796Y,D796Y,D796Y,T478K,T478K,S371F,S371F,S371F,S371F,S371F,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,P681H,P681H,S375F,D405N,D405N,D405N,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.1117T>C,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.79G>T,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 17.2x-fold lower (95% CI: 0.6x-0.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022.0 https://doi.org/10.1101/2022.06.05.494889 10.1101/2022.06.05.494889 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S monoclonal antibody serial passage escape In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C663, and to a lesser extent C613. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22679,22679,23039,23039,23040,24465,24466,24466,24468,24469,23521,23521,23522,23524,23524,23525,24130,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21641,24421,24421,24422,24423,24424,24424,24424,23060,23062,23062,23063,23063,22879,22879,22881,22882,22882,22882,23595,23596,23596,23598,23599,23853,23854,23071,23071,23074,23074,23075,23075,23202,23944,23944,23947,23948,23948,22992,22995,23048,22811,22812,22813,22813,22813,22673,22576,22577,22578,23604,23604,22686,23053,23053,23054,23054,23055,23055,22894,22896,22898,22992,23009,23010,23012,23013,24503,23399,23401,23401,23402,23403,23403 T95I,S373P,S373P,Q493R,Q493R,Q493R,N969K,N969K,N969K,N969K,N969K,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A27S,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N501Y,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,N440K,N440K,N679K,N679K,N679K,N679K,N679K,N764K,N764K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D796Y,D796Y,D796Y,D796Y,D796Y,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,S371L,G339D,G339D,G339D,P681H,P681H,S375F,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,G446S,G446S,G446S,S477N,E484A,E484A,E484A,E484A,L981F,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.79G>T,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.2941C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Leu981Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 1.5x-fold lower (95% CI: 0.05x-0.07x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022.0 https://doi.org/10.1101/2022.06.05.494889 10.1101/2022.06.05.494889 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417I YP_009724390.1:p.Lys417Ile S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S monoclonal antibody serial passage escape In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C682, and to a lesser extent C614 and C660 Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23071,23071,23074,23074,23075,23075,22992,23060,23062,23062,23063,23063 E484A,E484A,E484A,E484A,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,S477N,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1430G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Using molecular dynamics simulation, ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations. Zhang 2022.0 https://doi.org/10.1101/2022.06.05.493249 10.1101/2022.06.05.493249 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811 K417H YP_009724390.1:p.Lys417His S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S monoclonal antibody serial passage escape In vitro selection against class 1 antibody C682 Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects DARPin SR16m molecule had a 0.036x fold change in IC50 in B.1.351 Beta Chonira 2022.0 https://doi.org/10.1101/2022.05.30.493765 10.1101/2022.05.30.493765 35677079 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects DARPin SR16m molecule had a 6.7x fold change in IC50 in B.1.617.2 Delta Chonira 2022.0 https://doi.org/10.1101/2022.05.30.493765 10.1101/2022.05.30.493765 35677079 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects DARPin SR22 molecule had a 1.57x fold change in IC50 in B.1.351 Beta Chonira 2022.0 https://doi.org/10.1101/2022.05.30.493765 10.1101/2022.05.30.493765 35677079 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22696 K378N NC_045512.2:g.1134G>T YP_009724390.1:p.Lys378Asn S S surface glycoprotein S monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for mildly neutralizing COV2-2677 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects DARPin SR16m molecule had a 99.7x fold change in IC50 in B.1.617.2 Delta Chonira 2022.0 https://doi.org/10.1101/2022.05.30.493765 10.1101/2022.05.30.493765 35677079 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Trimeric proteins FSR16m had a 0.054x fold change in IC50 in B.1.351 Beta Chonira 2022.0 https://doi.org/10.1101/2022.05.30.493765 10.1101/2022.05.30.493765 35677079 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Trimeric proteins FSR16m had a 0.020x fold change in IC50 in B.1.617.2 Delta Chonira 2022.0 https://doi.org/10.1101/2022.05.30.493765 10.1101/2022.05.30.493765 35677079 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21786,21786,21789,22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403,24138,22298 G75V,T76I,T76I,L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G,T859N,R246_D253delinsN NC_045512.2:g.224G>T,NC_045512.2:g.227C>T,NC_045512.2:g.227C>T,NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2576C>A,NC_045512.2:g.737_757del YP_009724390.1:p.Gly75Val,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr859Asn,YP_009724390.1:p.Arg246_Asp253delinsAsn ,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Trimeric proteins FSR16m had a 0.038x fold change in IC50 in C.37 Lambda Chonira 2022.0 https://doi.org/10.1101/2022.05.30.493765 10.1101/2022.05.30.493765 35677079 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S antibody epitope effects Trimeric proteins FSR16m had a 0.025x fold change in IC50 in B.1.1.529 Omicron Chonira 2022.0 https://doi.org/10.1101/2022.05.30.493765 10.1101/2022.05.30.493765 35677079 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23013 E484V NC_045512.2:g.1451A>T YP_009724390.1:p.Glu484Val S S surface glycoprotein S monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23013 E484V NC_045512.2:g.1451A>T YP_009724390.1:p.Glu484Val S S surface glycoprotein S monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Trimeric proteins FSR22 had a 0.07x fold change in IC50 in B.1.351 Beta Chonira 2022.0 https://doi.org/10.1101/2022.05.30.493765 10.1101/2022.05.30.493765 35677079 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23013 E484V NC_045512.2:g.1451A>T YP_009724390.1:p.Glu484Val S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Trimeric proteins FSR22 had a 0.10x fold change in IC50 in B.1.617.2 Delta Chonira 2022.0 https://doi.org/10.1101/2022.05.30.493765 10.1101/2022.05.30.493765 35677079 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23012 E484R,E484R , YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg , S S surface glycoprotein S monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23012 E484R,E484R , YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg , S S surface glycoprotein S monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23012 E484R,E484R , YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg , S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21786,21786,21789,22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403,24138,22298 G75V,T76I,T76I,L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G,T859N,R246_D253delinsN NC_045512.2:g.224G>T,NC_045512.2:g.227C>T,NC_045512.2:g.227C>T,NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2576C>A,NC_045512.2:g.737_757del YP_009724390.1:p.Gly75Val,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr859Asn,YP_009724390.1:p.Arg246_Asp253delinsAsn ,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Trimeric proteins FSR22 had a 0.048x fold change in IC50 in C.37 Lambda Chonira 2022.0 https://doi.org/10.1101/2022.05.30.493765 10.1101/2022.05.30.493765 35677079 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S monoclonal antibody serial passage escape """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" Starr 2020.0 https://doi.org/10.1101/2020.11.30.405472 10.1101/2020.11.30.405472 33299993 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S monoclonal antibody serial passage escape """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" Starr 2020.0 https://doi.org/10.1101/2020.11.30.405472 10.1101/2020.11.30.405472 33299993 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S monoclonal antibody serial passage escape """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" Starr 2020.0 https://doi.org/10.1101/2020.11.30.405472 10.1101/2020.11.30.405472 33299993 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S antibody epitope effects Trimeric proteins FSR22 had a 0.0015x fold change in IC50 in B.1.1.529 Omicron Chonira 2022.0 https://doi.org/10.1101/2022.05.30.493765 10.1101/2022.05.30.493765 35677079 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23592 Q677P NC_045512.2:g.2030A>C YP_009724390.1:p.Gln677Pro S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Broad USA variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp S S surface glycoprotein S monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2499 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in D614G variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484T YP_009724390.1:p.Glu484Thr S S surface glycoprotein S monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484T YP_009724390.1:p.Glu484Thr S S surface glycoprotein S monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484T YP_009724390.1:p.Glu484Thr S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Cluster 5/Mink variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020.0 https://doi.org/10.1126/science.abd0831 10.1126/science.abd0831 32540904 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020.0 https://doi.org/10.1126/science.abd0831 10.1126/science.abd0831 32540904 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21762,21763,21763,21764,21765,21766,21766 H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del NC_045512.2:g.204_209del,,NC_045512.2:g.204_209del,,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del ,,,,,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Cluster 5/Mink variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020.0 https://doi.org/10.1126/science.abd0831 10.1126/science.abd0831 32540904 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020.0 https://doi.org/10.1038/s41586-020-2852-1 10.1038/s41586-020-2852-1 33045718 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020.0 https://doi.org/10.1126/science.abd0831 10.1126/science.abd0831 32540904 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020.0 https://doi.org/10.1038/s41586-020-2852-1 10.1038/s41586-020-2852-1 33045718 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020.0 https://doi.org/10.1126/science.abd0831 10.1126/science.abd0831 32540904 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25135 K1191N NC_045512.2:g.3573G>T YP_009724390.1:p.Lys1191Asn S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Florida variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020.0 https://doi.org/10.1038/s41586-020-2852-1 10.1038/s41586-020-2852-1 33045718 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020.0 https://doi.org/10.1126/science.abd0831 10.1126/science.abd0831 32540904 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020.0 https://doi.org/10.1038/s41586-020-2852-1 10.1038/s41586-020-2852-1 33045718 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S monoclonal antibody serial passage escape Class 2 antibodies C627, C602, C671, C643, and class 2/3 antibody C603 selected for the emergence of the E484K mutation in vitro. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Class 3 antibody C669 mildly selected for the emergence of the N440K mutation in vitro (in contrast to N440H which caused mild escape in Class 1/2 mAb C653). Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu S S surface glycoprotein S monoclonal antibody serial passage escape Positive selection (up to 23% of supernatant sequences) after C121 monoclonal antibody assay Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490V NC_045512.2:g.1468T>G YP_009724390.1:p.Phe490Val S S surface glycoprotein S monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21762,21763,21763,21764,21765,21766,21766 H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del NC_045512.2:g.204_209del,,NC_045512.2:g.204_209del,,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del ,,,,,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in B.1.258 variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Class 2/3 mAb C603 modestly selected for the emergence of this mutation in vitro. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490P YP_009724390.1:p.Phe490Pro S S surface glycoprotein S monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490P YP_009724390.1:p.Phe490Pro S S surface glycoprotein S monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490P YP_009724390.1:p.Phe490Pro S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Epsilon (B.1.427/429) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22018 W152C NC_045512.2:g.456G>T YP_009724390.1:p.Trp152Cys S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Epsilon (B.1.427/429) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Positive selection (up to 45% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, eliminated in subsequent passages Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>C,NC_045512.2:g.1038A>T YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser , S S surface glycoprotein S monoclonal antibody serial passage escape Positive selection (up to 30% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22597,22599 R346K,R346K,R346K ,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys ,, S S surface glycoprotein S monoclonal antibody serial passage escape Strong positive selection (up to 53% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020.0 https://doi.org/10.1038/s41586-020-2852-1 10.1038/s41586-020-2852-1 33045718 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020.0 https://doi.org/10.1038/s41586-020-2852-1 10.1038/s41586-020-2852-1 33045718 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600 S13I NC_045512.2:g.38G>T YP_009724390.1:p.Ser13Ile S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Epsilon (B.1.427/429) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020.0 https://doi.org/10.1038/s41586-020-2852-1 10.1038/s41586-020-2852-1 33045718 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S monoclonal antibody serial passage escape Class 2 mAb C627 modestly selected for the emergence of this mutation in vitro. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val S S surface glycoprotein S monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C102, C105 and C144 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020.0 https://doi.org/10.1038/s41586-020-2852-1 10.1038/s41586-020-2852-1 33045718 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22896 V445A NC_045512.2:g.1334T>C YP_009724390.1:p.Val445Ala S S surface glycoprotein S monoclonal antibody serial passage escape Escape variant 41% appearance in 2 passages against Regeneron monoclonal antibody RGN10987 @ 10ug/mL Baum 2020.0 https://doi.org/10.1126/science.abd0831 10.1126/science.abd0831 32540904 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in B.1.526.1 [B.1.637] variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp , S S surface glycoprotein S monoclonal antibody serial passage escape Escape variant 95% appearance in 2 passages against Regeneron monoclonal antibody RGN10934 @ 50ug/mL Baum 2020.0 https://doi.org/10.1126/science.abd0831 10.1126/science.abd0831 32540904 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22916 L452W YP_009724390.1:p.Leu452Trp S S surface glycoprotein S monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S monoclonal antibody serial passage escape Class 2/3 antibody C628 and class 2 antibody C643 selected for the emergence of the L452R mutation in vitro. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr , S S surface glycoprotein S monoclonal antibody serial passage escape Most effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02. Motozono 2021.0 https://doi.org/10.1016/j.chom.2021.06.006 10.1016/j.chom.2021.06.006 34171266 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80G NC_045512.2:g.239A>G YP_009724390.1:p.Asp80Gly S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in B.1.526.1 [B.1.637] variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val S S surface glycoprotein S monoclonal antibody serial passage escape Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL Baum 2020.0 https://doi.org/10.1126/science.abd0831 10.1126/science.abd0831 32540904 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val S S surface glycoprotein S monoclonal antibody serial passage escape Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL Baum 2020.0 https://doi.org/10.1126/science.abd0831 10.1126/science.abd0831 32540904 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val S S surface glycoprotein S monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486A YP_009724390.1:p.Phe486Ala S S surface glycoprotein S monoclonal antibody serial passage escape Most effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23664 A701V NC_045512.2:g.2102C>T YP_009724390.1:p.Ala701Val S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in lota (B.1.526) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val S S surface glycoprotein S monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val S S surface glycoprotein S monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486P YP_009724390.1:p.Phe486Pro S S surface glycoprotein S monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in lota (B.1.526) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486P YP_009724390.1:p.Phe486Pro S S surface glycoprotein S monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020.0 https://doi.org/10.1016/j.chom.2020.11.007 10.1016/j.chom.2020.11.007 33259788 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486P YP_009724390.1:p.Phe486Pro S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His S S surface glycoprotein S monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020.0 https://doi.org/10.1101/2020.11.30.405472 10.1101/2020.11.30.405472 33299993 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His S S surface glycoprotein S monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020.0 https://doi.org/10.1101/2020.11.30.405472 10.1101/2020.11.30.405472 33299993 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in lota (B.1.526) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486I NC_045512.2:g.1456T>A YP_009724390.1:p.Phe486Ile S S surface glycoprotein S monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020.0 https://doi.org/10.1101/2020.11.30.405472 10.1101/2020.11.30.405472 33299993 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486I NC_045512.2:g.1456T>A YP_009724390.1:p.Phe486Ile S S surface glycoprotein S monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020.0 https://doi.org/10.1101/2020.11.30.405472 10.1101/2020.11.30.405472 33299993 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486I NC_045512.2:g.1456T>A YP_009724390.1:p.Phe486Ile S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2:g.1456T>C YP_009724390.1:p.Phe486Leu S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317,22319,22320 D253G,D253G,D253G NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly ,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in lota (B.1.526) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23023 N487K NC_045512.2:g.1461T>G YP_009724390.1:p.Asn487Lys S S surface glycoprotein S monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, high ACE2 binding affinity loss Starr 2021.0 https://doi.org/10.1101/2021.02.17.431683 10.1101/2021.02.17.431683 33655250 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23897 Q779K NC_045512.2:g.2335C>A YP_009724390.1:p.Gln779Lys S S surface glycoprotein S monoclonal antibody serial passage escape Escape variant 20% appearance in 2 passages against Regeneron monoclonal antibody RGN10989 @ 50ug/mL Baum 2020.0 https://doi.org/10.1126/science.abd0831 10.1126/science.abd0831 32540904 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575 L5F NC_045512.2:g.13C>T YP_009724390.1:p.Leu5Phe S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in lota (B.1.526) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26029 Q213K NC_045512.2:g.637C>A YP_009724391.1:p.Gln213Lys ORF3a ORF3a ORF3a protein ORF3a T cell evasion "Variant causes complete loss of T cell line responsiveness to A*01:01-restricted CD8+ ORF3a epitope, which is otherwise ""consistently dominant and of high magnitude""." de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26029 Q213K NC_045512.2:g.637C>A YP_009724391.1:p.Gln213Lys ORF3a ORF3a ORF3a protein ORF3a T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*01:01. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23521,23522,23524,23524,23525 H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,, S S surface glycoprotein S anthropozoonotic events Six minks were intranasally infected with WA1 isolate, all developed this mutation during infection. Esclera 2021.0 https://doi.org/10.1101/2021.08.05.455290 10.1101/2021.08.05.455290 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S anthropozoonotic events First documented cases of domestic cat and dog infections with the B.1.1.7 strain. Hamer 2021.0 https://doi.org/10.1111/tbed.14122 10.1111/tbed.14122 33955193 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S anthropozoonotic events Unlike wild type or B.1.1.7, B.1.351 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. PG: The virus used in these expriments has a non-typical deletion+sub in the 242 region. Montagutelli 2021.0 https://doi.org/10.1101/2021.03.18.436013 10.1101/2021.03.18.436013 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S anthropozoonotic events Unlike wild type or B.1.1.7, P.1 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. Montagutelli 2021.0 https://doi.org/10.1101/2021.03.18.436013 10.1101/2021.03.18.436013 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525 N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,, S S surface glycoprotein S anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021.0 https://doi.org/10.1101/2021.01.19.21249592 10.1101/2021.01.19.21249592 33501468 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp ,,,,,,,,,,,,,,, S S surface glycoprotein S anthropozoonotic events These variants dominate in mink infections in North America, sometime supplemented with F486L. The Y453F variant found in other jurisdictions in mink infections is notably absent in North America. 2021.0 https://doi.org/10.1101/2021.03.18.21253734v3 10.1101/2021.03.18.21253734v3 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23593,23593 Q677H,Q677H NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His , S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Eta (B.1.525) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23071,23071,23074,23074,23075,23075 Y505H,Y505H,Y505H,Y505H,Y505H,Y505H ,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,, S S surface glycoprotein S anthropozoonotic events Observed first in a single tiger (cohort of 5), potential adaptation. McAloose 2020.0 https://doi.org/10.1128/mBio.02220-20 10.1128/mBio.02220-20 33051368 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile S S surface glycoprotein S anthropozoonotic events Observed first in a single tiger (cohort of 5), potential adaptation. McAloose 2020.0 https://doi.org/10.1128/mBio.02220-20 10.1128/mBio.02220-20 33051368 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2:g.1456T>C YP_009724390.1:p.Phe486Leu S S surface glycoprotein S anthropozoonotic events Observed in 4 separate mink farms in Denmark, but not humans, potential adaptation (diff set of farms than N501T). Oude Munnink 2020.0 https://doi.org/10.1126/science.abe5901 10.1126/science.abe5901 33172935 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Eta (B.1.525) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22344 G261D NC_045512.2:g.782G>A YP_009724390.1:p.Gly261Asp S S surface glycoprotein S anthropozoonotic events Multiple mink but no humans on one farm in Denmark, potential adaptation. Oude Munnink 2020.0 https://doi.org/10.1126/science.abe5901 10.1126/science.abe5901 33172935 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S anthropozoonotic events Observed in 4 separate mink farms in Denmark, and Y453F is circulating relatively widely in humans. Oude Munnink 2020.0 https://doi.org/10.1126/science.abe5901 10.1126/science.abe5901 33172935 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S anthropozoonotic events Oude Munnink 2020.0 https://doi.org/10.1126/science.abe5901 10.1126/science.abe5901 33172935 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23521,23522,23524,23524,23525 H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,, S S surface glycoprotein S anthropozoonotic events This mutation outside the receptor binding domain increases the virus transduction rate in tree shrew (Tupaia belangeri), (as it does in humans) according to pseudotyped VSV experiments. Li 2023.0 https://doi.org/10.1038/s41396-023-01368-2 10.1038/s41396-023-01368-2 36690780 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S anthropozoonotic events "This mutation (a.k.a. ""Doug"") outside the receptor binding domain, while highly favorable to improved human-human transmission, decreases transduction in naked mole-rat (Heterocephalus glaber) fibroblast and Japanese pipistrelle bat (Pipistrellus abramus) cell cultures using a pseudotyped VSV assay." Li 2023.0 https://doi.org/10.1038/s41396-023-01368-2 10.1038/s41396-023-01368-2 36690780 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21627 T22I NC_045512.2:g.65C>T YP_009724390.1:p.Thr22Ile S S surface glycoprotein S anthropozoonotic events This mutation outside the receptor binding domain, frequently observed in various human infection lineages, reduces the tropism of SARS-CoV-2 in F81 (cat kidney, Felis catus) and BHK-21 (golden hamster kidney, Mesocricetus auratus) cell line cultures using a pseudotyped VSV assay. Li 2023.0 https://doi.org/10.1038/s41396-023-01368-2 10.1038/s41396-023-01368-2 36690780 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile S S surface glycoprotein S anthropozoonotic events This mutation outside the receptor binding domain showed a decreased capacity to transduce PK-15 (pig kidney, Sus scrofa) and PaKi (black flying fox kidney, Pteropus alecto) cell line cultures using a pseudotyped VSV assay. Li 2023.0 https://doi.org/10.1038/s41396-023-01368-2 10.1038/s41396-023-01368-2 36690780 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21648 T29I NC_045512.2:g.86C>T YP_009724390.1:p.Thr29Ile S S surface glycoprotein S anthropozoonotic events This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay. Li 2023.0 https://doi.org/10.1038/s41396-023-01368-2 10.1038/s41396-023-01368-2 36690780 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24378,24378 S939F,S939F NC_045512.2:g.2816C>T, YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe , S S surface glycoprotein S anthropozoonotic events This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay. Li 2023.0 https://doi.org/10.1038/s41396-023-01368-2 10.1038/s41396-023-01368-2 36690780 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800 D80Y NC_045512.2:g.238G>T YP_009724390.1:p.Asp80Tyr S S surface glycoprotein S anthropozoonotic events This AA substitution outside the receptor binding domain in pseudotyped VSV promoted a 7.2% transduction rate in golden hamster cells, which was higher than that of human epithelial-like Huh-7 cells (6.6%). Li 2023.0 https://doi.org/10.1038/s41396-023-01368-2 10.1038/s41396-023-01368-2 36690780 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21855 S98F NC_045512.2:g.293C>T YP_009724390.1:p.Ser98Phe S S surface glycoprotein S anthropozoonotic events This mutation outside the receptor binding domain significantly enhanced the transduction rate in raccoon dog (Nyctereutes procyonoides) kidney (62.4%) and Rickett’s big-footed bat (Myotis pilosus) kidney (45.0%) cell cultures compared to epithelial-like human Huh-7 cells (38.9%). Li 2023.0 https://doi.org/10.1038/s41396-023-01368-2 10.1038/s41396-023-01368-2 36690780 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23587,23587,23587 Q675H,Q675H,Q675H NC_045512.2:g.2025G>C,,NC_045512.2:g.2025G>T YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His ,, S S surface glycoprotein S anthropozoonotic events This mutation outside the receptor binding domain significantly enhanced the ability of the pseudotyped VSV to infect fat-tailed gerbil (Pachyuromys duprasi) kidney cell cultures, with a transduction rate of 13.4%, close to the 15.7% in epithelial-like human Huh-7 cells while starting from a significantly lower wildtype (Wuhan-Hu-1 Spike VSVdeltaG psuedotype) rate. Li 2023.0 https://doi.org/10.1038/s41396-023-01368-2 10.1038/s41396-023-01368-2 36690780 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23009,23010,23012,23013 K417N,K417N,K417N,K417N,K417N,E484A,E484A,E484A,E484A NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,,,,,,, S S surface glycoprotein S outcome hazard ratio In Ontario, using a retrospective matched case (age, gender and onset date) study of 6,312 Omicron cases vs 8,875 Delta, the adjusted risk of hospitalization or death was 54% lower (HR=0.46, 95%CI: 0.27, 0.77) among Omicron cases, after adjusting for vaccination statis and time since 2nd shot. The ratio for >60yo was 0.55 (95%CI: 0.28-1.06), and <60yo was 0.30 (95%CI: 0.16-0.57). Ulloa 2021.0 https://doi.org/10.1101/2021.12.24.21268382v1.full 10.1101/2021.12.24.21268382v1.full not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death. 2021.0 https://doi.org/10.1503/cmaj.211248 10.1503/cmaj.211248 34610919 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death. 2021.0 https://doi.org/10.1503/cmaj.211248 10.1503/cmaj.211248 34610919 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21762,21763,21763,21764,21765,21766,21766 H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del NC_045512.2:g.204_209del,,NC_045512.2:g.204_209del,,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del ,,,,,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Eta (B.1.525) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance. Twohig 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death. 2021.0 https://doi.org/10.1503/cmaj.211248 10.1503/cmaj.211248 34610919 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance. Twohig 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio In Denmark, for the period Jan 1 to Jun 27, 2021, Delta variant was associated with increased an risk ratio of 2.83 [95% CI 2.02–3.98] for hospitalization. Bager 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Compared to Alpha (B.1.1.7) variant, odds of progressing to severe disease were 1.24-fold (95% CI: 1.11-1.39) higher for Beta. Odds of progressing to critical disease were 1.49-fold (95% CI: 1.13-1.97) higher. Odds of COVID-19 death were 1.57-fold (95% CI: 1.03-2.43) higher. Abu-Raddad 2021.0 https://doi.org/10.1101/2021.08.02.21261465 10.1101/2021.08.02.21261465 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22317,22319,22320,23399,23401,23401,23402,23403,23403 T95I,D253G,D253G,D253G,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,, S S surface glycoprotein S outcome hazard ratio B.1.526 (Iota) substantially increased IFR in older adults: by 46% (95% CI: 7.4 – 84%) among 45-64 year-olds, 82% (95% CI: 20 – 140%) among 65-74 year-olds, and 62% (95% CI: 45 – 80%) among 75+ during Nov 2020 – Apr 2021, compared to baseline IFR estimated for preexisting variants. [minimum clade defining mutations listed] Yang 2021.0 https://doi.org/10.1101/2021.08.04.21261596 10.1101/2021.08.04.21261596 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021.0 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021.0 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021.0 https://doi.org/10.2139/ssrn.3792894 10.2139/ssrn.3792894 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021.0 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Zeta (P.2) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021.0 https://doi.org/10.2139/ssrn.3792894 10.2139/ssrn.3792894 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021.0 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 10.2807/1560-7917.ES.2021.26.16.2100348 33890566 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021.0 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021.0 https://doi.org/10.2139/ssrn.3792894 10.2139/ssrn.3792894 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021.0 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 10.2807/1560-7917.ES.2021.26.16.2100348 33890566 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021.0 https://doi.org/10.48550/arXiv.2104.05560 10.48550/arXiv.2104.05560 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021.0 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021.0 https://doi.org/10.2139/ssrn.3792894 10.2139/ssrn.3792894 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021.0 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 10.2807/1560-7917.ES.2021.26.16.2100348 33890566 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021.0 https://doi.org/10.48550/arXiv.2104.05560 10.48550/arXiv.2104.05560 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23664 A701V NC_045512.2:g.2102C>T YP_009724390.1:p.Ala701Val S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel this viral variant contributes to variant algorithm Zeta (P.2) from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021.0 https://doi.org/10.1038/s41586-021-03426-1 10.1038/s41586-021-03426-1 33723411 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021.0 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021.0 https://doi.org/10.2139/ssrn.3792894 10.2139/ssrn.3792894 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021.0 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 10.2807/1560-7917.ES.2021.26.16.2100348 33890566 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021.0 https://doi.org/10.48550/arXiv.2104.05560 10.48550/arXiv.2104.05560 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021.0 https://doi.org/10.1038/s41586-021-03426-1 10.1038/s41586-021-03426-1 33723411 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio 341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). Frampton 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021.0 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021.0 https://doi.org/10.2139/ssrn.3792894 10.2139/ssrn.3792894 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021.0 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 10.2807/1560-7917.ES.2021.26.16.2100348 33890566 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23592 Q677P NC_045512.2:g.2030A>C YP_009724390.1:p.Gln677Pro S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel this viral variant contributes to variant algorithm Zeta (P.2) from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021.0 https://doi.org/10.48550/arXiv.2104.05560 10.48550/arXiv.2104.05560 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021.0 https://doi.org/10.1038/s41586-021-03426-1 10.1038/s41586-021-03426-1 33723411 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio 341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). Frampton 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. Graham 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021.0 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021.0 https://doi.org/10.2139/ssrn.3792894 10.2139/ssrn.3792894 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021.0 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 10.2807/1560-7917.ES.2021.26.16.2100348 33890566 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021.0 https://doi.org/10.48550/arXiv.2104.05560 10.48550/arXiv.2104.05560 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021.0 https://doi.org/10.1038/s41586-021-03426-1 10.1038/s41586-021-03426-1 33723411 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio 341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). Frampton 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23593,23593 Q677H,Q677H NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His , S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel this viral variant contributes to variant algorithm Zeta (P.2) from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. Graham 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio The mortality hazard ratio associated with infection with [B.1.1.7] compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community (54906 matched pairs of participants who tested positive for SARS-CoV-2 in pillar 2 between 1 October 2020 and 29 January 2021). In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases. Challen 2021.0 https://doi.org/10.1136/bmj.n579 10.1136/bmj.n579 33687922 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525 L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication] Ribas Freitas 2021.0 https://doi.org/10.1101/2021.04.13.21255281 10.1101/2021.04.13.21255281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525 L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication] Ribas Freitas 2021.0 https://doi.org/10.1101/2021.04.13.21255281 10.1101/2021.04.13.21255281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525 L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases). Funk 2021.0 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 10.2807/1560-7917.ES.2021.26.16.2100348 33890566 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525 L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication] Ribas Freitas 2021.0 https://doi.org/10.1101/2021.04.13.21255281 10.1101/2021.04.13.21255281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525 L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases). Funk 2021.0 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 10.2807/1560-7917.ES.2021.26.16.2100348 33890566 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525 L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio In the Parana state of Brazil, patients aged 20-29 years experienced a tripling of their case fatality rate (CFR), from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling comparing February to January in 2021. Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil. [this is somewhat indirect evidence that assume greatly increasing proportion of P.1 cases in March (70%) compared to February, but the first official ID of P.1 in Parana state (Feb 16th) may be due to testing procedures rather than actual prevalence] Santos de Oliviera 2021.0 https://doi.org/10.1101/2021.03.24.21254046 10.1101/2021.03.24.21254046 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S outcome hazard ratio On average across 7 European countries studied, using B.1.351 defining mutations: Significant shift to infection in those without pre-existing conditions (79.6% vs 89% for non-VOC cases). Significant increase in hospitalization rate (19.3% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.3% vs 0.6% for non-VOC cases). PG: seems to be different notations around the LAL deletion, using the minimal shared definition to catch as many as possible. Funk 2021.0 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 10.2807/1560-7917.ES.2021.26.16.2100348 33890566 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel this viral variant contributes to variant algorithm Zeta (P.2) from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681R NC_045512.2:g.2042C>G YP_009724390.1:p.Pro681Arg S S surface glycoprotein S virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. [PG: Inferred by conservative AA substitution of described P681H] Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp S S surface glycoprotein S virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23604,23604 N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.2042C>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,, S S surface glycoprotein S virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020.0 https://doi.org/10.1038/s41467-020-19808-4 10.1038/s41467-020-19808-4 33243994 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020.0 https://doi.org/10.1038/s41467-020-19808-4 10.1038/s41467-020-19808-4 33243994 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S virion structure "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Yurkovetskiy 2020.0 https://doi.org/10.1016/j.cell.2020.09.032 10.1016/j.cell.2020.09.032 32991842 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020.0 https://doi.org/10.1038/s41467-020-19808-4 10.1038/s41467-020-19808-4 33243994 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel this viral variant contributes to variant algorithm Zeta (P.2) from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S virion structure "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Yurkovetskiy 2020.0 https://doi.org/10.1016/j.cell.2020.09.032 10.1016/j.cell.2020.09.032 32991842 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S virion structure "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Weissman 2020.0 https://doi.org/10.1101/2020.07.22.20159905 10.1101/2020.07.22.20159905 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020.0 https://doi.org/10.1038/s41467-020-19808-4 10.1038/s41467-020-19808-4 33243994 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S virion structure "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Yurkovetskiy 2020.0 https://doi.org/10.1016/j.cell.2020.09.032 10.1016/j.cell.2020.09.032 32991842 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S virion structure "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Weissman 2020.0 https://doi.org/10.1101/2020.07.22.20159905 10.1101/2020.07.22.20159905 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S virion structure Estimated free energy change (ddG) for this variant is 2.5 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S virion structure CryoEM analysis of B.1.1.7 demonstrates an increased propensity for 'up', receptor accessible conformation of the Spike protein trimer. Cai 2021.0 https://doi.org/10.1101/2021.04.13.439709 10.1101/2021.04.13.439709 33880477 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801 L18F,D80A NC_045512.2:g.52C>T,NC_045512.2:g.239A>C YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala , S S surface glycoprotein S virion structure The L18F and D80A of the B.1.351 lineage lead to reconfiguration of the N-terminal segment despite the disulfide between Cys16 and Cys136 that partly anchors the N-terminal peptide. The most consequential changes are probably from the triple residue deletion... which causes a shift of the nearby loop 144-155 and must also reconfigure the adjacent disorder loop (residues 246-260), both of which form part of the neutralizing epitopes...bringing large changes in the antigenic surface in this region. Cai 2021.0 https://doi.org/10.1101/2021.04.13.439709 10.1101/2021.04.13.439709 33880477 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S virion structure CryoEM reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the “up” position. Wang 2021.0 https://doi.org/10.1101/2021.03.01.433466 10.1101/2021.03.01.433466 33688656 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24642 T1027I NC_045512.2:g.3080C>T YP_009724390.1:p.Thr1027Ile S S surface glycoprotein S virion structure Estimated free energy change (ddG) for this variant is 1.51 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel this viral variant contributes to variant algorithm Zeta (P.2) from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly S S surface glycoprotein S virion structure Estimated free energy change (ddG) for this variant is 0.98 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23521,23522,23524,23524,23525 H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,, S S surface glycoprotein S virion structure Estimated free energy change (ddG) for this variant is 0.87 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S virion structure Estimated free energy change (ddG) for this variant is 0.69 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21974 D138Y NC_045512.2:g.412G>T YP_009724390.1:p.Asp138Tyr S S surface glycoprotein S virion structure Estimated free energy change (ddG) for this variant is 0.43 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S virion structure Estimated free energy change (ddG) for this variant is 0.22 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala S S surface glycoprotein S virion structure Estimated that there is no free energy change (ddG) for this variant (i.e. same stability as wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp S S surface glycoprotein S virion structure Estimated that there is very little free energy change (ddG. -0.02 kcal/mol) for this variant (i.e. approx. same stability as wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23664 A701V NC_045512.2:g.2102C>T YP_009724390.1:p.Ala701Val S S surface glycoprotein S virion structure Estimated free energy change (ddG) for this variant is -0.33 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S virion structure Estimated free energy change (ddG) for this variant is -0.6 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Gamma (P.1) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S virion structure Estimated free energy change (ddG) for this variant is -0.64 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S virion structure Estimated free energy change (ddG) for this variant is -0.67 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22132 R190S NC_045512.2:g.570G>T YP_009724390.1:p.Arg190Ser S S surface glycoprotein S virion structure Estimated free energy change (ddG) for this variant is -0.69 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S virion structure Estimated free energy change (ddG) for this variant is -0.86 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021.0 https://doi.org/10.1101/2021.03.24.436850 10.1101/2021.03.24.436850 33791700 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22679,22679,23009,23010,23012,23013 S373P,S373P,E484A,E484A,E484A,E484A NC_045512.2:g.1117T>C,,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,,,, S S surface glycoprotein S transmissibility On December 7, 2021 the estimate of Omicron effective reproduction rate (Rt) is 3.12 [presumably R0 is higher], compared to 1.12 for the dominant Delta VOC at that time. [shorthand of variant list shraed by all contemporary BA lineage used here] 2021.0 https://doi.org/10.47326/ocsat.dashboard.2021.1.0 10.47326/ocsat.dashboard.2021.1.0 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23604,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,P681R,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,, S S surface glycoprotein S transmissibility Normalized for particle number, on ACE2.293T cells showed that the B.1.617 spike protein was >2-fold increase in infectivity relative to D614G wild type. Tada 2021.0 https://doi.org/10.1101/2021.05.14.444076 10.1101/2021.05.14.444076 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Gamma (P.1) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990,21993,21995,23011,23012,23399,23401,23401,23402,23403,23403 Y145del,Y145del,H146del,H146del,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.436_438del,NC_045512.2:g.436_438del,,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.His146del,YP_009724390.1:p.His146del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,, S S surface glycoprotein S transmissibility Normalized for particle number, on ACE2.293T cells showed that the B.1.618 spike protein was about as infective as D614G wild type. Tada 2021.0 https://doi.org/10.1101/2021.05.14.444076 10.1101/2021.05.14.444076 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,, S S surface glycoprotein S transmissibility Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase] Tada 2021.0 https://doi.org/10.1101/2021.05.14.444076 10.1101/2021.05.14.444076 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,, S S surface glycoprotein S transmissibility Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase] Tada 2021.0 https://doi.org/10.1101/2021.05.14.444076 10.1101/2021.05.14.444076 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,, S S surface glycoprotein S transmissibility The L452R mutation increased the infectivity more than two-fold in these conditions. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S transmissibility The combination caused a 3-fold increase in infectivity relative to D614G wild type. [compare to 3.5x for L452R alone] Tada 2021.0 https://doi.org/10.1101/2021.05.14.444076 10.1101/2021.05.14.444076 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23401,23402,23403,23403 E484Q,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S transmissibility Using a pseudovirus assay, RBD-specific mutation E484Q did not significantly confer infectivity advantage to the spike particles. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S transmissibility Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,23399,23401,23401,23402,23403,23403 T95I,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S transmissibility Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,23399,23401,23401,23402,23403,23403 T95I,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S transmissibility Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,23399,23401,23401,23402,23403,23403 E156_R158delinsG,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.467_472del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S transmissibility Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 conferred a nearly two-fold infectivity advantage to the spike particles. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Gamma (P.1) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 E156_R158delinsG,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.467_472del,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~2x infectivity advantage to the spike particles. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,23012,23399,23401,23401,23402,23403,23403 E156_R158delinsG,E484Q,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.467_472del,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,, S S surface glycoprotein S transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~4x infectivity advantage to the spike particles. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 E156_R158delinsG,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.467_472del,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,, S S surface glycoprotein S transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x infectivity advantage to the spike particles [less than L452R or E484Q alone working with the delins]. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22028,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 T95I,E156_R158delinsG,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.467_472del,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,, S S surface glycoprotein S transmissibility Using a pseudovirus assay, this lineage defining mutation combination from B.1.617.3 conferred a ~4.5x infectivity advantage to the spike particles. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21717,23011,23012,23593,23593,24224 Q52R,E484K,E484K,Q677H,Q677H,F888L NC_045512.2:g.155A>G,,NC_045512.2:g.1450G>A,NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T,NC_045512.2:g.2662T>C YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu ,,,,, S S surface glycoprotein S transmissibility The B.1.525 appears to have poor transmissibility when in competition with B.1.1.7 and other circulating strains in Denmark (early 2021). Albertsen 2021.0 https://www.covid19genomics.dk/2021-05-08_data-overview.html#b1525 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S transmissibility The N440K variant produced ten times higher infectious viral titers than a prevalent A2a strain, and over 1000 folds higher titers than a much less prevalent A3i strain prototype in Caco2 cells. Interestingly, A3i strain showed the highest viral RNA levels, but the lowest infectious titers in the culture supernatants, indicating the absence of correlation between the RNA content and the infectivity of the sample. Tandel 2021.0 https://doi.org/10.1101/2021.04.30.441434 10.1101/2021.04.30.441434 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021.0 https://doi.org/10.1126/science.abg3055 10.1126/science.abg3055 33658326 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021.0 https://doi.org/10.1126/science.abg3055 10.1126/science.abg3055 33658326 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021.0 https://doi.org/10.1101/2021.04.16.21255459 10.1101/2021.04.16.21255459 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021.0 https://doi.org/10.1126/science.abg3055 10.1126/science.abg3055 33658326 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Gamma (P.1) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021.0 https://doi.org/10.1101/2021.04.16.21255459 10.1101/2021.04.16.21255459 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021.0 https://doi.org/10.1101/2021.04.06.21254923 10.1101/2021.04.06.21254923 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021.0 https://doi.org/10.1126/science.abg3055 10.1126/science.abg3055 33658326 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021.0 https://doi.org/10.1101/2021.04.16.21255459 10.1101/2021.04.16.21255459 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021.0 https://doi.org/10.1101/2021.04.06.21254923 10.1101/2021.04.06.21254923 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49) Buchan et al. (2021) ttps://www.medrxiv.org/content/10.1101/2021.03.31.21254502v1 Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants. Lindstrøm 2021.0 https://doi.org/10.1101/2021.03.29.21254122 10.1101/2021.03.29.21254122 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021.0 https://doi.org/10.1126/science.abg3055 10.1126/science.abg3055 33658326 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021.0 https://doi.org/10.1101/2021.04.16.21255459 10.1101/2021.04.16.21255459 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021.0 https://doi.org/10.1101/2021.04.06.21254923 10.1101/2021.04.06.21254923 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49) Buchan et al. (2021) ttps://www.medrxiv.org/content/10.1101/2021.03.31.21254502v1 Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants. Lindstrøm 2021.0 https://doi.org/10.1101/2021.03.29.21254122 10.1101/2021.03.29.21254122 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23664 A701V NC_045512.2:g.2102C>T YP_009724390.1:p.Ala701Val S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Beta (B.1.351) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks. Munitz 2021.0 https://doi.org/10.1016/j.xcrm.2021.100264 10.1016/j.xcrm.2021.100264 33899031 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021.0 https://doi.org/10.1126/science.abg3055 10.1126/science.abg3055 33658326 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021.0 https://doi.org/10.1101/2021.04.16.21255459 10.1101/2021.04.16.21255459 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021.0 https://doi.org/10.1101/2021.04.06.21254923 10.1101/2021.04.06.21254923 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49) Buchan et al. (2021) ttps://www.medrxiv.org/content/10.1101/2021.03.31.21254502v1 Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants. Lindstrøm 2021.0 https://doi.org/10.1101/2021.03.29.21254122 10.1101/2021.03.29.21254122 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks. Munitz 2021.0 https://doi.org/10.1016/j.xcrm.2021.100264 10.1016/j.xcrm.2021.100264 33899031 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S transmissibility Based on 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020, Rt of B.1.1.7 was 1.35x (95% CI 1.02-1.69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Graham 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525 L18F,T20N,P26S,D138Y,R190S,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S transmissibility The relative transmissibility of P.1 estimated at the national level (Italy) varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. PG: variant list has been abbreviated due to mixed K417 bases in this lineage, potential miscalls of deletions Stefanelli 2021.0 https://doi.org/10.1101/2021.04.06.21254923 10.1101/2021.04.06.21254923 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,, S S surface glycoprotein S transmissibility Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429. Deng 2021.0 https://doi.org/10.1101/2021.03.07.21252647 10.1101/2021.03.07.21252647 33758899 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,, S S surface glycoprotein S transmissibility Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429. Deng 2021.0 https://doi.org/10.1101/2021.03.07.21252647 10.1101/2021.03.07.21252647 33758899 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Beta (B.1.351) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,, S S surface glycoprotein S transmissibility "Lineages bearing these spike mutations comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the ""California"" or ""West Coast"" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI:1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020." Peng 2021.0 https://doi.org/10.1093/cid/ciab283 10.1093/cid/ciab283 33788923 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,, S S surface glycoprotein S transmissibility Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure. Pearson 2021.0 https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,, S S surface glycoprotein S transmissibility Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure. Pearson 2021.0 https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,, S S surface glycoprotein S transmissibility 36,590 variant-specific RT-PCR tests were performed on samples collected between April 12 and May 7, 2021 in France to compare variant spread. Compared to January to March 2021, B.1.351 variant had a significant transmission advantage over B.1.1.7 in some regions (15.1 to 16.1% in Île-de-France and 16.1 to 18.8% in Hauts-de-France). This shift in transmission advantage is consistent with the immune evasion abilities of B.1.351 and the high levels of immunization in these regions. Roquebert 2021.0 https://doi.org/10.1101/2021.05.12.21257130 10.1101/2021.05.12.21257130 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Beta (B.1.351) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn , S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K NC_045512.2:g.1380T>A,,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Beta (B.1.351) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn , S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22280 L242_L244del NC_045512.2:g.725_733del YP_009724390.1:p.Leu242_Leu244del S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Beta (B.1.351) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn , S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Beta (B.1.351) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn , S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Beta (B.1.351) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Beta (B.1.351) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn , S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K NC_045512.2:g.1380T>A,,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn , S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K NC_045512.2:g.1380T>A,,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022.0 https://doi.org/10.1101/2022.08.17.504313 10.1101/2022.08.17.504313 36032981 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,23399,23401,23401,23402,23403,23403,23944,23944,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22894,22896,22898,23048,23521,23521,23522,23524,23524,23525,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,24130,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22673,22679,22679,22686,22992,21846,22992,22995,23202,21987,21990,23071,23071,23074,23074,23075,23075 A67V,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G446S,G446S,G446S,G496S,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N856K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,S371L,S373P,S373P,S375F,S477N,T95I,T478K,T478K,T547K,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H NC_045512.2:g.200C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2568C>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1640C>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness 4th antigenic exposure with Omicron (B.1.1.529 [BA.1])(n=29) infection increased variant specific plasma antibody and memory B cell responses as well as overall increased strain specific memory in individuals aged 22 –79 years, median age=33.5 years. Data collected 2.4 months after 3rd vaccination. Wang 2022.0 https://doi.org/10.1101/2022.08.11.503601 10.1101/2022.08.11.503601 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23062,23062,23063,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness 3rd exposure to antigen by Delta (B.1.617.2) (n=24) breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a 3rd mRNA vaccine dose in individuals aged 21 –63 years, median age=30 years. Data collected 5.5 months after 2nd vaccination. Wang 2022.0 https://doi.org/10.1101/2022.08.11.503601 10.1101/2022.08.11.503601 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Omicron (B.1.1.529 [BA.1]) have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022.0 https://doi.org/10.1101/2022.06.01.494385 10.1101/2022.06.01.494385 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22784,22785,22786,22786,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Omicron BA.2 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022.0 https://doi.org/10.1101/2022.06.01.494385 10.1101/2022.06.01.494385 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Omicron BA.3 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022.0 https://doi.org/10.1101/2022.06.01.494385 10.1101/2022.06.01.494385 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Omicron BA.4 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022.0 https://doi.org/10.1101/2022.06.01.494385 10.1101/2022.06.01.494385 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Alpha (B.1.1.7) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Omicron BA.5 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022.0 https://doi.org/10.1101/2022.06.01.494385 10.1101/2022.06.01.494385 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~100x folds more significant in 3 individuals. Arora 2022.0 https://doi.org/10.1038/s41423-022-00870-5 10.1038/s41423-022-00870-5 35581351 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness All 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 729 NT50. Arora 2022.0 https://doi.org/10.1038/s41423-022-00870-5 10.1038/s41423-022-00870-5 35581351 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness All 10 individuals with 3 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 3319 NT50. Arora 2022.0 https://doi.org/10.1038/s41423-022-00870-5 10.1038/s41423-022-00870-5 35581351 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21588,21848,22132,22191,22600,22600,22907,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24138,24368 P9L,E96Q,R190S,I210T,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T859N,D936H NC_045512.2:g.26C>T,NC_045512.2:g.286G>C,NC_045512.2:g.570G>T,NC_045512.2:g.629T>C,NC_045512.2:g.1038A>C,NC_045512.2:g.1038A>T,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2576C>A,NC_045512.2:g.2806G>C YP_009724390.1:p.Pro9Leu,YP_009724390.1:p.Glu96Gln,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Ile210Thr,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr859Asn,YP_009724390.1:p.Asp936His ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in B.1.640.2 variant was ~1000x folds more significant in 8 individuals. Arora 2022.0 https://doi.org/10.1038/s41423-022-00870-5 10.1038/s41423-022-00870-5 35581351 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21588,21848,22132,22191,22600,22600,22907,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24138,24368 P9L,E96Q,R190S,I210T,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T859N,D936H NC_045512.2:g.26C>T,NC_045512.2:g.286G>C,NC_045512.2:g.570G>T,NC_045512.2:g.629T>C,NC_045512.2:g.1038A>C,NC_045512.2:g.1038A>T,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2576C>A,NC_045512.2:g.2806G>C YP_009724390.1:p.Pro9Leu,YP_009724390.1:p.Glu96Gln,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Ile210Thr,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr859Asn,YP_009724390.1:p.Asp936His ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1.640.2 variant was ~5.6x folds more significant in 9 individuals. Arora 2022.0 https://doi.org/10.1038/s41423-022-00870-5 10.1038/s41423-022-00870-5 35581351 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~17.5x folds more significant in 9 individuals. Arora 2022.0 https://doi.org/10.1038/s41423-022-00870-5 10.1038/s41423-022-00870-5 35581351 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23041,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness 100% of the 5 8‑month‑old male R3P1-E4 antibody treated mice suvived 14 days after infection while only 60% the control group mice survived 5 days post infection. Li 2022.0 https://doi.org/10.1186/s13578-022-00794-7 10.1186/s13578-022-00794-7 35581593 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23041,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Lung viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~2266x fold drop in the R3P1-E4 antibody in comparison to the IgG control. Li 2022.0 https://doi.org/10.1186/s13578-022-00794-7 10.1186/s13578-022-00794-7 35581593 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23041,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Trachea viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~750x fold drop in the R3P1-E4 antibody in comparison to the IgG control. Li 2022.0 https://doi.org/10.1186/s13578-022-00794-7 10.1186/s13578-022-00794-7 35581593 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Alpha (B.1.1.7) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Omicron MK-4482 had no statistically significant change. Rosenke 2022.0 https://doi.org/10.1172/jci.insight.160108 10.1172/jci.insight.160108 35579953 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Delta MK-4482 had ~4x fold drop. Rosenke 2022.0 https://doi.org/10.1172/jci.insight.160108 10.1172/jci.insight.160108 35579953 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Beta MK-4482 had ~1.75x fold drop. Rosenke 2022.0 https://doi.org/10.1172/jci.insight.160108 10.1172/jci.insight.160108 35579953 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Alpha MK-4482 had ~2.75x fold drop. Rosenke 2022.0 https://doi.org/10.1172/jci.insight.160108 10.1172/jci.insight.160108 35579953 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21987,21990,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23039,23040,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Omicron (a.k.a. B.1.1.529) Spike pseudotyped VSV and Vero E6 cells has somewhat reduced neutralization (2.7x) vs wild type with monoclonal antibody Sotrovimab (a.k.a. VIR-7831). [delins at 214 omitted for syntax compatibility] Cathcart 2021.0 https://doi.org/10.1101/2021.03.09.434607v9 10.1101/2021.03.09.434607v9 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22597,22599 R346K,R346K,R346K ,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys ,, S S surface glycoprotein S pharmaceutical effectiveness This individual mutation, which has emerged in some Omicron sequences, has a 0.7x reduction in neutralization activity with Sotrovimab in a VSV model on Vero E6 cells. [Omicron sequences with R346K may very well have a non-additive neutralization rather than 2.7x+0.7x = 3.4x] Cathcart 2021.0 https://doi.org/10.1101/2021.03.09.434607v9 10.1101/2021.03.09.434607v9 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp ,, S S surface glycoprotein S pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 1.2x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021.0 https://doi.org/10.1101/2021.03.09.434607v9 10.1101/2021.03.09.434607v9 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 0.7x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021.0 https://doi.org/10.1101/2021.03.09.434607v9 10.1101/2021.03.09.434607v9 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 2.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021.0 https://doi.org/10.1101/2021.03.09.434607v9 10.1101/2021.03.09.434607v9 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Alpha (B.1.1.7) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 1.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021.0 https://doi.org/10.1101/2021.03.09.434607v9 10.1101/2021.03.09.434607v9 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 0.9x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021.0 https://doi.org/10.1101/2021.03.09.434607v9 10.1101/2021.03.09.434607v9 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555. Rappazzo 2021.0 https://doi.org/10.1126/science.abf4830 10.1126/science.abf4830 33495307 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23060,23062,23062,23063,23063 Y489H,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,, S S surface glycoprotein S pharmaceutical effectiveness This Spike pseudotype for Day 146 virus from a chronically infected patient was completely resistent to REGN10933. The variant had a 4-fold decrease in REGN10987 neutralization sensitivity (2nd component of the Regeneron mAb cocktail). Clark 2021.0 https://doi.org/10.1016/j.cell.2021.03.027 10.1016/j.cell.2021.03.027 33831372 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23062,23062,23063,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness This Spike pseudotype for Day 152 virus from a chronically infected patient was completely resistent to REGN10933. Clark 2021.0 https://doi.org/10.1016/j.cell.2021.03.027 10.1016/j.cell.2021.03.027 33831372 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness P.1 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with Lilly mAb combination LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of P.1. There was also escape from neutralization of P.1 by REGN10933 (one of 2 in Regeneron's mAb cocktail) and a modest reduction in neutralization of P.1 by AstraZeneca's AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized P.1 with all reaching a plateau at 100% neutralization; interestingly, ADG30 showed a slight increase of neutralization of P.1. S309 Vir was largely unaffected, although for several viruses, including P.1, the antibody failed to completely neutralize, conceivably reflecting incomplete glycosylation at N343, since the sugar interaction is key to binding of this antibody. Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness B.1.351 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of B.1.351. There was also escape from neutralization of B.1.351 by REGN10933 and a modest reduction in neutralization of B.1.351 by AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized B.1.351. Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,24506 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,S982A NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala ,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Lilly's LY-CoV16 showed marked reduction in neutralization of B.1.1.7. Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro. Liu 2021.0 https://doi.org/10.1101/2021.02.16.431305 10.1101/2021.02.16.431305 33619479 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro. Liu 2021.0 https://doi.org/10.1101/2021.02.16.431305 10.1101/2021.02.16.431305 33619479 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from B.1.351. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness VSV pseudotype B.1.351 entry mediated by the S proteins of the B.1.351 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness VSV pseudotype P.1 entry mediated by the S proteins of the P.1 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Cell fusion proficiency was slight impaired. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812,23011,23012,23060,23062,23062,23063,23063 K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from P.1. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency. McCallum 2021.0 https://doi.org/10.1101/2021.03.31.437925 10.1101/2021.03.31.437925 33821281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency. McCallum 2021.0 https://doi.org/10.1101/2021.03.31.437925 10.1101/2021.03.31.437925 33821281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~5x binding against this isolated mutation. Cligavimab lost ~4x binding against this isolated mutation. Regdanvimab lost ~4x binding against this isolated mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S pharmaceutical effectiveness COR-101 lost ~6x binding against this isolated mutation. Estesevimab lost ~100x binding against this isolated mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21762,21763,21763,21764,21765,21766,21766 H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del,H69_V70del NC_045512.2:g.204_209del,,NC_045512.2:g.204_209del,,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del ,,,,,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Alpha (B.1.1.7) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S pharmaceutical effectiveness COR-101 lost ~16x binding against this isolated mutation. Estesevimab lost ~16x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val S S surface glycoprotein S pharmaceutical effectiveness COR-101 lost ~50x binding against this isolated mutation. Estesevimab lost ~8x binding against this isolated mutation. Sotrovimab lost ~30x binding against this isolated mutation. Tixagevimab lost ~15x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~16x binding against this isolated mutation. Casirivimab lost ~16x binding against this isolated mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln S S surface glycoprotein S pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~20x binding against this isolated mutation. Casirivimab lost ~4x binding against this isolated mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro S S surface glycoprotein S pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Regdanvimab lost ~32x binding against this isolated mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681R NC_045512.2:g.2042C>G YP_009724390.1:p.Pro681Arg S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Delta (B.1.617.2+AY.x) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S pharmaceutical effectiveness COR-101 lost ~8x binding against this isolated mutation. Regdanvimab lost ~6x binding against this isolated mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23120 A520S NC_045512.2:g.1558G>T YP_009724390.1:p.Ala520Ser S S surface glycoprotein S pharmaceutical effectiveness CR3022 (SARS-targeting mAb) cross-reactivity lost ~4x binding against this isolated mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,22811,22812,22813,22813,22813 E484K,E484K,K417N,K417N,K417N,K417N,K417N ,NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~32x binding against this double mutation. COR-101 lost ~160x binding against this double mutation. Casirivimab lost ~16x binding against this double mutation. Estesevimab lost ~32x binding against this double mutation. Regdanvimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S pharmaceutical effectiveness COR-101 lost ~12x binding against this double mutation. Casirivimab lost ~64x binding against this double mutation. Cligavimab lost ~6x binding against this double mutation. Estesevimab lost ~10x binding against this double mutation. Imdevimab lost ~5x binding against this double mutation. Regdanvimab lost ~8x binding against this double mutation. Sotrovimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S pharmaceutical effectiveness Casirivimab lost >50x binding against this mutation. Hoffman 2021.0 https://doi.org/10.1016/j.celrep.2021.109017 10.1016/j.celrep.2021.109017 33857422 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23011,23012 S477N,E484K,E484K NC_045512.2:g.1430G>A,,NC_045512.2:g.1450G>A YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys ,, S S surface glycoprotein S pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~10x binding against this double mutation. Tixagevimab lost ~16x binding against this double mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23011,23012 N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1450G>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys ,,,,,, S S surface glycoprotein S pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~64x binding against this double mutation. COR-101 lost ~50x binding against this double mutation. Casirivimab lost ~250x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~32x binding against this double mutation. Tixagevimab lost ~10x binding against this double mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,22995 T478K,T478K NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys , S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Delta (B.1.617.2+AY.x) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,22811,22812,22813,22813,22813 N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,,,,,,, S S surface glycoprotein S pharmaceutical effectiveness COR-101 lost ~20x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~6x binding against this double mutation. M396 lost ~10x binding against this double mutation. Engelhart 2021.0 https://doi.org/10.1101/2021.04.27.440939 10.1101/2021.04.27.440939 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S environmental condition stability No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively. Schuit 2021.0 https://doi.org/10.1093/infdis/jiab171 10.1093/infdis/jiab171 33822064 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S environmental condition stability No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively. Schuit 2021.0 https://doi.org/10.1093/infdis/jiab171 10.1093/infdis/jiab171 33822064 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S environmental condition stability Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks. Meister 2021.0 https://doi.org/10.1093/infdis/jiab260 10.1093/infdis/jiab260 33993274 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala S S surface glycoprotein S environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23604,23604 N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.2042C>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,, S S surface glycoprotein S environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S environmental condition stability Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S environmental condition stability Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S environmental condition stability Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks. Meister 2021.0 https://doi.org/10.1093/infdis/jiab260 10.1093/infdis/jiab260 33993274 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Delta (B.1.617.2+AY.x) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>C,NC_045512.2:g.531G>T,NC_045512.2:g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile ,, S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:01. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681R NC_045512.2:g.2042C>G YP_009724390.1:p.Pro681Arg S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in B.1.617 [India] variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22926 L455S NC_045512.2:g.1364T>C YP_009724390.1:p.Leu455Ser S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.45 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in B.1.617 [India] variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417I YP_009724390.1:p.Lys417Ile S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.39 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in B.1.617 [India] variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.32 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp ,, S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.3 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Omicron (B.1.1.529 [BA.1]) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,22995 T478K,T478K NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys , S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Omicron (B.1.1.529 [BA.1]) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917 L452Q NC_045512.2:g.1355T>A YP_009724390.1:p.Leu452Gln S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.27 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Omicron (B.1.1.529 [BA.1]) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Omicron (B.1.1.529 [BA.1]) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.25 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846 T95I NC_045512.2:g.284C>T YP_009724390.1:p.Thr95Ile S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel polymorphism is detected in Omicron (B.1.1.529 [BA.1]) variant from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486P YP_009724390.1:p.Phe486Pro S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.22 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22624 N354K NC_045512.2:g.1062C>A YP_009724390.1:p.Asn354Lys S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22629 K356R NC_045512.2:g.1067A>G YP_009724390.1:p.Lys356Arg S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel this viral variant contributes to variant algorithm Omicron (B.1.1.529 [BA.1]) from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22583 V341I NC_045512.2:g.1021G>A YP_009724390.1:p.Val341Ile S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23108 E516Q NC_045512.2:g.1546G>C YP_009724390.1:p.Glu516Gln S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22784,22785,22786,22786 R408S,R408S,R408S,R408S NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser ,,, S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23075 Y505Q YP_009724390.1:p.Tyr505Gln S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 E156_R158delinsG,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.467_472del,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2x. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>C,NC_045512.2:g.531G>T,NC_045512.2:g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile ,, S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:03. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe S S surface glycoprotein S antibody epitope effects Using the Agena MassARRAY® SARS-CoV-2 Variant Panel this viral variant contributes to variant algorithm Omicron (B.1.1.529 [BA.1]) from 391 RNA specimens. Hernandez 2022.0 https://doi.org/10.1101/2022.05.28.22275691 10.1101/2022.05.28.22275691 35665019 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Utilizing shark derived vnarbodies, S375F mutation on Omicron RBD disrupts the structure of β-strand, which inhibits binding with 20G6. 20G6 binds to a hidden epitope on RBD which is highly conserved in sarbecoviruses. Feng 2022.0 https://doi.org/10.1002/smtd.202200387 10.1002/smtd.202200387 35583124 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22632 R357K NC_045512.2:g.1070G>A YP_009724390.1:p.Arg357Lys S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.18 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against B.1 variant and was used to determine neutralizing antibodytitres. There was a 6.76x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 2.06x fold increase in antibody response pre-reinfection. There was a 8.18x fold increase in antibody response during reinfection. Shete 2022.0 https://doi.org/10.1101/2022.05.12.491584 10.1101/2022.05.12.491584 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22623 N354S YP_009724390.1:p.Asn354Ser S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.17 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K NC_045512.2:g.1380T>A,,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys ,,,,, S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Delta variant and was used to determine neutralizing antibodytitres. There was a 24.63x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 4.21x fold increase in antibody response pre-reinfection. There was a 39.27x fold increase in antibody response during reinfection. Shete 2022.0 https://doi.org/10.1101/2022.05.12.491584 10.1101/2022.05.12.491584 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912,22912,22916 L452M,L452M,L452M NC_045512.2:g.1354C>A,,NC_045512.2:g.1354C>A YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met ,, S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23071,23071,23074,23074,23075,23075 Y505H,Y505H,Y505H,Y505H,Y505H,Y505H ,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,, S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22597,22599,22599 R346T,R346T,R346T,R346T ,NC_045512.2:g.1037G>C,,NC_045512.2:g.1037G>C YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr ,,, S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.15 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Omicron variant and was used to determine neutralizing antibodytitres. There was a 114.84x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 6.61x fold increase in antibody response pre-reinfection. There was a 1194.9x fold increase in antibody response during reinfection. Shete 2022.0 https://doi.org/10.1101/2022.05.12.491584 10.1101/2022.05.12.491584 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22573,22574,22576,22577 G339H,G339H,G339H,G339H ,,, YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His ,,, S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.15 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects BnAb 002-S21F2 IC50 on the Alpha (B.1.1.7) variant is 1.0x fold the wildtype in 42 COVI. Kumar 2022.0 https://doi.org/10.1101/2022.05.13.491770 10.1101/2022.05.13.491770 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22627,22629 K356T,K356T ,NC_045512.2:g.1067A>C YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr , S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.14 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects BnAb 002-S21F2 IC50 on the Beta (B.1.351) variant is 0.4x fold the wildtype. Kumar 2022.0 https://doi.org/10.1101/2022.05.13.491770 10.1101/2022.05.13.491770 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22622 N354D NC_045512.2:g.1060A>G YP_009724390.1:p.Asn354Asp S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.13 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.13 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects BnAb 002-S21F2 IC50 on the Gamma (P.1) variant is 0.6x fold the wildtype. Kumar 2022.0 https://doi.org/10.1101/2022.05.13.491770 10.1101/2022.05.13.491770 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23102 S514T NC_045512.2:g.1540T>A YP_009724390.1:p.Ser514Thr S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22597,22599 R346K,R346K,R346K ,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys ,, S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects BnAb 002-S21F2 IC50 on the Delta (B.1.617.2) variant is 0.6x fold the wildtype. Kumar 2022.0 https://doi.org/10.1101/2022.05.13.491770 10.1101/2022.05.13.491770 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22661 V367I NC_045512.2:g.1099G>A YP_009724390.1:p.Val367Ile S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23048 G496S NC_045512.2:g.1486G>A YP_009724390.1:p.Gly496Ser S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22907 Y449H NC_045512.2:g.1345T>C YP_009724390.1:p.Tyr449His S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects BnAb 002-S21F2 IC50 on the Omicron BA.1 variant is 1.0x fold the wildtype. Kumar 2022.0 https://doi.org/10.1101/2022.05.13.491770 10.1101/2022.05.13.491770 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22577 G339N YP_009724390.1:p.Gly339Asn S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.11 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>C,NC_045512.2:g.531G>T,NC_045512.2:g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile ,, S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:02. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22784,22785,22786,22786,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects BnAb 002-S21F2 IC50 on the Omicron BA.2 variant is 0.8x fold the wildtype. Kumar 2022.0 https://doi.org/10.1101/2022.05.13.491770 10.1101/2022.05.13.491770 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.11 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22766 I402V NC_045512.2:g.1204A>G YP_009724390.1:p.Ile402Val S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Alpha (B.1.1.7) has an IC50 fold change of 1.19x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811 K417H YP_009724390.1:p.Lys417His S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486A YP_009724390.1:p.Phe486Ala S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Beta (B.1.351) has an IC50 fold change of 0.13x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22784 R408G YP_009724390.1:p.Arg408Gly S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.09 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775,21846,24863 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I,H1101D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T,NC_045512.2:g.3301C>G YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.His1101Asp ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Kappa (B.1.617.1) has an IC50 fold change of 0.13x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Delta (B.1.617.2) has an IC50 fold change of 0.57x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22598 R346E YP_009724390.1:p.Arg346Glu S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.08 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.1 has an IC50 fold change of 0.30x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22851 T430I NC_045512.2:g.1289C>T YP_009724390.1:p.Thr430Ile S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22784,22785,22786,22786,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.2 has an IC50 fold change of 0.07x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893,22893 K444T,K444T ,NC_045512.2:g.1331A>C YP_009724390.1:p.Lys444Thr,YP_009724390.1:p.Lys444Thr , S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22964 I468V NC_045512.2:g.1402A>G YP_009724390.1:p.Ile468Val S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.44x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22907 Y449N NC_045512.2:g.1345T>A YP_009724390.1:p.Tyr449Asn S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Beta (B.1.351) has an IC50 fold change of 0.15x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22745 V395I NC_045512.2:g.1183G>A YP_009724390.1:p.Val395Ile S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23115 L518Q NC_045512.2:g.1553T>A YP_009724390.1:p.Leu518Gln S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775,21846,24863 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I,H1101D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T,NC_045512.2:g.3301C>G YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.His1101Asp ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Kappa (B.1.617.1) has an IC50 fold change of 2.3x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>C,NC_045512.2:g.531G>T,NC_045512.2:g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile ,, S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:02. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Delta (B.1.617.2) has an IC50 fold change of 0.15x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.1 has an IC50 fold change of 0.08x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486H YP_009724390.1:p.Phe486His S S surface glycoprotein S gene expression increase Experimentally, Spike gene expression increased 0.05 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22784,22785,22786,22786,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.2 has an IC50 fold change of 0.04x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29239,29239 M322I,M322I NC_045512.2:g.966G>T,NC_045512.2:g.966G>A YP_009724397.2:p.Met322Ile,YP_009724397.2:p.Met322Ile , N N nucleocapsid phosphoprotein N T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. Agerer 2021.0 https://doi.org/10.1126/sciimmunol.abg6461 10.1126/sciimmunol.abg6461 33664060 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29266,29266 L331F,L331F NC_045512.2:g.993G>C,NC_045512.2:g.993G>T YP_009724397.2:p.Leu331Phe,YP_009724397.2:p.Leu331Phe , N N nucleocapsid phosphoprotein N T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. Agerer 2021.0 https://doi.org/10.1126/sciimmunol.abg6461 10.1126/sciimmunol.abg6461 33664060 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28310 P13S NC_045512.2:g.37C>T YP_009724397.2:p.Pro13Ser N N nucleocapsid phosphoprotein N T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*27:05. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29247 T325I NC_045512.2:g.974C>T YP_009724397.2:p.Thr325Ile N N nucleocapsid phosphoprotein N T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile N N nucleocapsid phosphoprotein N T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile N N nucleocapsid phosphoprotein N T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs 35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.39x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile N N nucleocapsid phosphoprotein N T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser N N nucleocapsid phosphoprotein N T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser N N nucleocapsid phosphoprotein N T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser N N nucleocapsid phosphoprotein N T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28307,28308,28309,28309,28310,28310,28311,28311 P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L NC_045512.2:g.38C>T,,,NC_045512.2:g.38C>T,,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T, YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu ,,,,,,, N N nucleocapsid phosphoprotein N T cell evasion Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13). de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28310 P13S NC_045512.2:g.37C>T YP_009724397.2:p.Pro13Ser N N nucleocapsid phosphoprotein N T cell evasion Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13). de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile N N nucleocapsid phosphoprotein N T cell evasion "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser N N nucleocapsid phosphoprotein N T cell evasion "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29247 T325I NC_045512.2:g.974C>T YP_009724397.2:p.Thr325Ile N N nucleocapsid phosphoprotein N T cell evasion Variant causes partial loss of T cell line responsiveness and CTL killing ability by B*40:01-restricted CD8+ N epitope MEVTPSGTWL 322-331. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs 35B5. Beta (B.1.351) has an IC50 fold change of 0.13x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526 A2S NC_045512.2:g.4G>T YP_009724393.1:p.Ala2Ser M M membrane glycoprotein M immunosuppression variant emergence Emergent as 16% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing. Avanzato 2020.0 https://doi.org/10.1016/j.cell.2020.10.049 10.1016/j.cell.2020.10.049 33248470 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28877,29148 G204R,I292T ,NC_045512.2:g.875T>C YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Ile292Thr , N N nucleocapsid phosphoprotein N reinfection Reinfection in a September 2020 of a 61yo female Brazilian HCW, no hospitalization required in first or second infection. Genome also has one Spike mutation of unknown significance, S:p.Q675H Amorim 2021.0 https://doi.org/10.3201/eid2706.210558 10.3201/eid2706.210558 33871331 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28655,28877 D128H,G204R NC_045512.2:g.382G>C, YP_009724397.2:p.Asp128His,YP_009724397.2:p.Gly204Arg , N N nucleocapsid phosphoprotein N reinfection Reinfection in an October 2020 of a 40yo female Brazilian HCW, no hospitalization required in first or second infection. Poor overall genome quality. Genome also has one Spike mutation that would become a defining mutation in lineage P.2, S:p.V1176F Amorim 2021.0 https://doi.org/10.3201/eid2706.210558 10.3201/eid2706.210558 33871331 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S convalescent plasma binding 1.33x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S convalescent plasma binding 1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23060,23062,23062,23063,23063 D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,, S S surface glycoprotein S convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23271 D614G,D614G,D614G,D614G,D614G,D614G,A570D NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp ,,,,,, S S surface glycoprotein S convalescent plasma binding 1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23604,23604 D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,,, S S surface glycoprotein S convalescent plasma binding 1.26x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23709 D614G,D614G,D614G,D614G,D614G,D614G,T716I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile ,,,,,, S S surface glycoprotein S convalescent plasma binding 1.58x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24506 D614G,D614G,D614G,D614G,D614G,D614G,S982A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala ,,,,,, S S surface glycoprotein S convalescent plasma binding 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775,21846,24863 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I,H1101D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T,NC_045512.2:g.3301C>G YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.His1101Asp ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs 35B5. Kappa (B.1.617.1) has an IC50 fold change of 0.68x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24914 D614G,D614G,D614G,D614G,D614G,D614G,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His ,,,,,, S S surface glycoprotein S convalescent plasma binding 1.96x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma binding This variant combination (representing B.1.1.7 aka Alpha) showed a 1.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614 D614G,D614G,D614G,D614G,D614G,D614G,L18F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe ,,,,,, S S surface glycoprotein S convalescent plasma binding 1.66x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Compare to decreased binding in full Spike variant complements for major lineages containing this variant subset: 0.96x (B.1.351 aka Beta), 0.77x (P.1 aka Gamma). Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21801 D614G,D614G,D614G,D614G,D614G,D614G,D80A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala ,,,,,, S S surface glycoprotein S convalescent plasma binding 2.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22206 D614G,D614G,D614G,D614G,D614G,D614G,D215G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly ,,,,,, S S surface glycoprotein S convalescent plasma binding 2.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S convalescent plasma binding 1.97x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S convalescent plasma binding 1.53x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22811,22812,22813,22813,22813 D614G,D614G,D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,,,,,,,, S S surface glycoprotein S convalescent plasma binding 2.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23011,23012 D614G,D614G,D614G,D614G,D614G,D614G,E484K,E484K NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys ,,,,,,, S S surface glycoprotein S convalescent plasma binding 1.42x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23664 D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,, S S surface glycoprotein S convalescent plasma binding 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs 35B5. Delta (B.1.617.2) has an IC50 fold change of 0.87x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614,21801,23060,23062,23062,23063,23063,22206,22811,22812,22813,22813,22813,23011,23012,23664 D614G,D614G,D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma binding This variant combination (representing B.1.351 aka Beta) showed a 1.04x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, in contrast to the largely positive binding values for each individual mutation that comprises the set. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21621 D614G,D614G,D614G,D614G,D614G,D614G,T20N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn ,,,,,, S S surface glycoprotein S convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21638 D614G,D614G,D614G,D614G,D614G,D614G,P26S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser ,,,,,, S S surface glycoprotein S convalescent plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21974 D614G,D614G,D614G,D614G,D614G,D614G,D138Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr ,,,,,, S S surface glycoprotein S convalescent plasma binding 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22132 D614G,D614G,D614G,D614G,D614G,D614G,R190S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser ,,,,,, S S surface glycoprotein S convalescent plasma binding 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22812,22812 D614G,D614G,D614G,D614G,D614G,D614G,K417T,K417T NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1250A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr ,,,,,,, S S surface glycoprotein S convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525 D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,, S S surface glycoprotein S convalescent plasma binding 1.48x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24642 D614G,D614G,D614G,D614G,D614G,D614G,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile ,,,,,, S S surface glycoprotein S convalescent plasma binding 1.56x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642 D614G,D614G,D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma binding This variant combination (representing P.1 aka Gamma) showed a 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21575 D614G,D614G,D614G,D614G,D614G,D614G,L5F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe ,,,,,, S S surface glycoprotein S convalescent plasma binding No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs 35B5. Omicron BA.1 has an IC50 fold change of 0.38x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21846 D614G,D614G,D614G,D614G,D614G,D614G,T95I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile ,,,,,, S S surface glycoprotein S convalescent plasma binding No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D614G,D614G,D253G,D253G,D253G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly ,,,,,,,, S S surface glycoprotein S convalescent plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21575,21846,22317,22319,22320,23011,23012,23664 D614G,D614G,D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma binding This variant combination (representing lineage B.1.526) showed a 1.02x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21600 D614G,D614G,D614G,D614G,D614G,D614G,S13I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile ,,,,,, S S surface glycoprotein S convalescent plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22018 D614G,D614G,D614G,D614G,D614G,D614G,W152C NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys ,,,,,, S S surface glycoprotein S convalescent plasma binding 1.15x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,,,,,, S S surface glycoprotein S convalescent plasma binding 2.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21600,22018,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma binding This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, indicating ablated marginal effect from L452R. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma binding This variant combination (representing lineage B.1.617) showed a 1.22x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma binding This variant combination (representing lineage B.1.617.1) showed a 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma binding This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.92x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22784,22785,22786,22786,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs 35B5. Omicron BA.2 has an IC50 fold change of 0.09x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28853 S194T NC_045512.2:g.580T>A YP_009724397.2:p.Ser194Thr N N nucleocapsid phosphoprotein N anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021.0 https://doi.org/10.1101/2021.01.19.21249592 10.1101/2021.01.19.21249592 33501468 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28881 R203M NC_045512.2:g.608G>T YP_009724397.2:p.Arg203Met N N nucleocapsid phosphoprotein N RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows most increase in RNA content of any N mutation tested, suggesting that this mutation improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021.0 https://doi.org/10.1101/2021.08.05.455082 10.1101/2021.08.05.455082 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28879 S202R NC_045512.2:g.606T>G YP_009724397.2:p.Ser202Arg N N nucleocapsid phosphoprotein N RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows major increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021.0 https://doi.org/10.1101/2021.08.05.455082 10.1101/2021.08.05.455082 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28869 P199L NC_045512.2:g.596C>T YP_009724397.2:p.Pro199Leu N N nucleocapsid phosphoprotein N RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021.0 https://doi.org/10.1101/2021.08.05.455082 10.1101/2021.08.05.455082 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the 47D10. Alpha (B.1.1.7) has an IC50 fold change of 0.40x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22784,22785,22786,22786,23009,23010,23012,23013,23060,23062,23062,23063,23063 R408S,R408S,R408S,R408S,E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a study of 481 vaccinees going from lowest to highest infection rate, 2 doses of CoronaVac and 1 dose of BNT162b2 had the lowest infection rate at 6.3%, then it was 3 doses of BNT162b2 having a infection rate of 16.6%. 2 and 3 doses of CoronaVac had 48.6% and 20.6% infection rate respectively. 2 doses of BNT162b2 has the highest infection rate at 49.2%. Zhou 2022.0 https://doi.org/10.1101/2022.05.09.491254 10.1101/2022.05.09.491254 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23062,23062,23063,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,, S S surface glycoprotein S vaccine efficacy Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2). Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23062,23062,23063,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,, S S surface glycoprotein S vaccine efficacy Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2). Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23062,23062,23063,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,, S S surface glycoprotein S vaccine efficacy In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous. Braeye 2022.0 https://doi.org/10.1101/2022.05.09.22274623 10.1101/2022.05.09.22274623 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23062,23062,23063,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,, S S surface glycoprotein S vaccine efficacy Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2). Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>C,NC_045512.2:g.531G>T,NC_045512.2:g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile ,, S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type C*07:02. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs 47D10. Beta (B.1.351) has an IC50 fold change of 0.88x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23062,23062,23063,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,, S S surface glycoprotein S vaccine efficacy In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous. Braeye 2022.0 https://doi.org/10.1101/2022.05.09.22274623 10.1101/2022.05.09.22274623 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23062,23062,23063,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,, S S surface glycoprotein S vaccine efficacy In sera from 17 sero-positive blood donors, and 18 months post-infection (May 2020) sera from 17 health care workers in Sweden, a 40x drop in neutralization by Omicron (B.1.1.529) pseudotyped lentivirus was observed in HEK293T cells using the First WHO International Standard (20/136). Median IC50 reduction was ~6x for the blood donors, and ~4.5x for the health care workers. Sheward 2021.0 https://drive.google.com/file/d/1CuxmNYj5cpIuxWXhjjVmuDqntxXwlfXQ/view grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021.0 https://doi.org/10.1101/2021.08.06.21261707 10.1101/2021.08.06.21261707 34401884 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021.0 https://doi.org/10.1101/2021.08.06.21261707 10.1101/2021.08.06.21261707 34401884 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021.0 https://doi.org/10.1056/NEJMoa2108891 10.1056/NEJMoa2108891 34289274 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021.0 https://doi.org/10.1101/2021.08.06.21261707 10.1101/2021.08.06.21261707 34401884 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775,21846,24863 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I,H1101D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T,NC_045512.2:g.3301C>G YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.His1101Asp ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs 47D10. Kappa (B.1.617.1) has an IC50 fold change of 80.2x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021.0 https://doi.org/10.1056/NEJMoa2108891 10.1056/NEJMoa2108891 34289274 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021.0 https://doi.org/10.15585/mmwr.mm7034e4 10.15585/mmwr.mm7034e4 34437521 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021.0 https://doi.org/10.1101/2021.08.06.21261707 10.1101/2021.08.06.21261707 34401884 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021.0 https://doi.org/10.1056/NEJMoa2108891 10.1056/NEJMoa2108891 34289274 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021.0 https://doi.org/10.15585/mmwr.mm7034e4 10.15585/mmwr.mm7034e4 34437521 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021.0 https://doi.org/10.15585/mmwr.mm7034e3 10.15585/mmwr.mm7034e3 34437519 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021.0 https://doi.org/10.1101/2021.08.06.21261707 10.1101/2021.08.06.21261707 34401884 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021.0 https://doi.org/10.1056/NEJMoa2108891 10.1056/NEJMoa2108891 34289274 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs 47D10. Delta (B.1.617.2) has an IC50 fold change of 46.5x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021.0 https://doi.org/10.15585/mmwr.mm7034e4 10.15585/mmwr.mm7034e4 34437521 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021.0 https://doi.org/10.15585/mmwr.mm7034e3 10.15585/mmwr.mm7034e3 34437519 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021.0 https://doi.org/10.1101/2021.06.28.21259420 10.1101/2021.06.28.21259420 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021.0 https://doi.org/10.1101/2021.08.06.21261707 10.1101/2021.08.06.21261707 34401884 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021.0 https://doi.org/10.1056/NEJMoa2108891 10.1056/NEJMoa2108891 34289274 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021.0 https://doi.org/10.15585/mmwr.mm7034e4 10.15585/mmwr.mm7034e4 34437521 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021.0 https://doi.org/10.15585/mmwr.mm7034e3 10.15585/mmwr.mm7034e3 34437519 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021.0 https://doi.org/10.1101/2021.06.28.21259420 10.1101/2021.06.28.21259420 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role. Tang 2021.0 https://doi.org/10.1101/2021.08.11.21261885 10.1101/2021.08.11.21261885 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs 47D10. Omicron BA.1 has an IC50 fold change of 1.26x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021.0 https://doi.org/10.1101/2021.08.06.21261707 10.1101/2021.08.06.21261707 34401884 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021.0 https://doi.org/10.1056/NEJMoa2108891 10.1056/NEJMoa2108891 34289274 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021.0 https://doi.org/10.15585/mmwr.mm7034e4 10.15585/mmwr.mm7034e4 34437521 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021.0 https://doi.org/10.15585/mmwr.mm7034e3 10.15585/mmwr.mm7034e3 34437519 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021.0 https://doi.org/10.1101/2021.06.28.21259420 10.1101/2021.06.28.21259420 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role. Tang 2021.0 https://doi.org/10.1101/2021.08.11.21261885 10.1101/2021.08.11.21261885 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). Chia 2021.0 https://doi.org/10.1101/2021.07.28.21261295 10.1101/2021.07.28.21261295 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021.0 https://doi.org/10.1101/2021.08.06.21261707 10.1101/2021.08.06.21261707 34401884 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22784,22785,22786,22786,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Neutralization of the bsAbs 47D10. Omicron BA.2 has an IC50 fold change of 0.08x. Yuan 2022.0 https://doi.org/10.1101/2022.05.11.491588 10.1101/2022.05.11.491588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021.0 https://doi.org/10.1056/NEJMoa2108891 10.1056/NEJMoa2108891 34289274 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021.0 https://doi.org/10.15585/mmwr.mm7034e4 10.15585/mmwr.mm7034e4 34437521 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021.0 https://doi.org/10.15585/mmwr.mm7034e3 10.15585/mmwr.mm7034e3 34437519 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021.0 https://doi.org/10.1101/2021.06.28.21259420 10.1101/2021.06.28.21259420 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role. Tang 2021.0 https://doi.org/10.1101/2021.08.11.21261885 10.1101/2021.08.11.21261885 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). Chia 2021.0 https://doi.org/10.1101/2021.07.28.21261295 10.1101/2021.07.28.21261295 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy The incidence rate of Covid-19 during the Delta-dominant period (Jul-Aug 2021) was lower for late vaccinated (49.0/1000 person-years) [formerly placebo] versus early vaccinated (77.1/1000 person-years) participants in the Moderna mRNA-1273 Phase 3 trials, representing a 36.4% VE reduction (95% CI 17.1%-51.5%). There were fewer severe Covid-19 cases in the late group (6; 6.2/1000 person-years) than early (13; 3.3/1000 person-years), representing a 46.0% reduction (95% CI −52.4%-83.2%). Three Covid-19 related hospitalizations occurred with two resulting deaths in the early group. Baden 2021.0 https://doi.org/10.1101/2021.09.17.21263624 10.1101/2021.09.17.21263624 34611666 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given] Puranik 2021.0 https://doi.org/10.1101/2021.08.06.21261707 10.1101/2021.08.06.21261707 34401884 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given] Puranik 2021.0 https://doi.org/10.1101/2021.08.06.21261707 10.1101/2021.08.06.21261707 34401884 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant. Lopez Bernal 2021.0 https://doi.org/10.1056/NEJMoa2108891 10.1056/NEJMoa2108891 34289274 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given] Puranik 2021.0 https://doi.org/10.1101/2021.08.06.21261707 10.1101/2021.08.06.21261707 34401884 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant. Lopez Bernal 2021.0 https://doi.org/10.1056/NEJMoa2108891 10.1056/NEJMoa2108891 34289274 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%). Nasreen 2021.0 https://doi.org/10.1101/2021.06.28.21259420 10.1101/2021.06.28.21259420 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S vaccine efficacy Protection against symptomatic infection caused by Beta/Gamma (assumed by combined presence of N501Y and E484K) was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%). Nasreen 2021.0 https://doi.org/10.1101/2021.06.28.21259420 10.1101/2021.06.28.21259420 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H NC_045512.2:g.284C>T,,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 69 test-positive were Mu. Two dose vaccine efficacy against Mu was 90.4% (73.9-96.5%), one dose VE was 45.8% (0.0-88.9%). Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,22992,23011,23012,23664 L5F,S477N,E484K,E484K,A701V NC_045512.2:g.13C>T,NC_045512.2:g.1430G>A,,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val ,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 114 test-positive were Iota. Two dose vaccine efficacy against Iota was 95.7 (81.7-99.0%), one dose VE was 88.8 (0.7-98.7)%. Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 349 test-positive were Gamma. Two dose vaccine efficacy against Gamma was 95.5 (90.9-97.8%), one dose VE was 74.2 (43.8-88.1%). Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,, S S surface glycoprotein S vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 583 test-positive were Epsilon. Two dose vaccine efficacy against Epsilon was 97.6 (90.2-99.4%), one dose VE was 76.3 (48.1-89.1%). Bruxvoort 2021.0 https://doi.org/10.1101/2021.09.29.21264199 10.1101/2021.09.29.21264199 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S vaccine efficacy In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape by lineage Alpha [defined here as N501Y positive, but E484K negative]. Chung 2021.0 https://doi.org/10.1136/bmj.n1943 10.1136/bmj.n1943 34417165 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S vaccine efficacy In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape due to E484K [given Dec 2020-Apr 2021 time frame of the study, this is assumed to entail both Beta and Gamma lineages]. Chung 2021.0 https://doi.org/10.1136/bmj.n1943 10.1136/bmj.n1943 34417165 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S antibody epitope effects No detectable fold drop in IC50 of P22A-1D1. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S viral load Viral load from oral swabs from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482. Rosenke 2022.0 https://doi.org/10.1172/jci.insight.160108 10.1172/jci.insight.160108 35579953 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S viral load Viral load from lung tissue from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482. Rosenke 2022.0 https://doi.org/10.1172/jci.insight.160108 10.1172/jci.insight.160108 35579953 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23604 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,P681R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg ,,,,,,, S S surface glycoprotein S viral load In 9 infected hamsters each for B.1 and B.1.617.1, no significant change in viral load or subgenomic RNA levels were detected. Yadav 2021.0 https://doi.org/10.1101/2021.05.05.442760 10.1101/2021.05.05.442760 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021.0 https://doi.org/10.1101/2021.05.03.441080 10.1101/2021.05.03.441080 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021.0 https://doi.org/10.1101/2021.05.03.441080 10.1101/2021.05.03.441080 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021.0 https://doi.org/10.1101/2021.04.30.442222 10.1101/2021.04.30.442222 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021.0 https://doi.org/10.1101/2021.05.03.441080 10.1101/2021.05.03.441080 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S antibody epitope effects No detectable fold drop in IC50 of P22A-1D1. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021.0 https://doi.org/10.1101/2021.04.30.442222 10.1101/2021.04.30.442222 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021.0 https://doi.org/10.1101/2021.02.24.21251989 10.1101/2021.02.24.21251989 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021.0 https://doi.org/10.1101/2021.05.03.441080 10.1101/2021.05.03.441080 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021.0 https://doi.org/10.1101/2021.04.30.442222 10.1101/2021.04.30.442222 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021.0 https://doi.org/10.1101/2021.02.24.21251989 10.1101/2021.02.24.21251989 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." Couzens 2021.0 https://doi.org/10.1101/2021.04.02.21254832 10.1101/2021.04.02.21254832 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021.0 https://doi.org/10.1101/2021.05.03.441080 10.1101/2021.05.03.441080 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021.0 https://doi.org/10.1101/2021.04.30.442222 10.1101/2021.04.30.442222 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021.0 https://doi.org/10.1101/2021.02.24.21251989 10.1101/2021.02.24.21251989 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." Couzens 2021.0 https://doi.org/10.1101/2021.04.02.21254832 10.1101/2021.04.02.21254832 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>C,NC_045512.2:g.531G>T,NC_045512.2:g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile ,, S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DPB1*04:01. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change. Teyssou 2021.0 https://doi.org/10.1101/2021.03.21.21253498 10.1101/2021.03.21.21253498 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021.0 https://doi.org/10.1101/2021.05.03.441080 10.1101/2021.05.03.441080 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021.0 https://doi.org/10.1101/2021.04.30.442222 10.1101/2021.04.30.442222 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021.0 https://doi.org/10.1101/2021.02.24.21251989 10.1101/2021.02.24.21251989 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." Couzens 2021.0 https://doi.org/10.1101/2021.04.02.21254832 10.1101/2021.04.02.21254832 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change. Teyssou 2021.0 https://doi.org/10.1101/2021.03.21.21253498 10.1101/2021.03.21.21253498 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively. Roquebert 2021.0 https://doi.org/10.1101/2021.03.19.21253971 10.1101/2021.03.19.21253971 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021.0 https://doi.org/10.1101/2021.05.03.441080 10.1101/2021.05.03.441080 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021.0 https://doi.org/10.1101/2021.04.30.442222 10.1101/2021.04.30.442222 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021.0 https://doi.org/10.1101/2021.02.24.21251989 10.1101/2021.02.24.21251989 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." Couzens 2021.0 https://doi.org/10.1101/2021.04.02.21254832 10.1101/2021.04.02.21254832 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change. Teyssou 2021.0 https://doi.org/10.1101/2021.03.21.21253498 10.1101/2021.03.21.21253498 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively. Roquebert 2021.0 https://doi.org/10.1101/2021.03.19.21253971 10.1101/2021.03.19.21253971 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S viral load The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036). Song 2021.0 https://doi.org/10.1101/2021.05.04.21256655 10.1101/2021.05.04.21256655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S viral load Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission. Plante 2020.0 https://doi.org/10.1038/s41586-020-2895-3 10.1038/s41586-020-2895-3 33106671 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,, S S surface glycoprotein S viral load Swab samples N/NP viral RNA is approximately 2-fold higher in B.1.427/B.1.429 than in non-variant viruses. Deng 2021.0 https://doi.org/10.1101/2021.03.07.21252647 10.1101/2021.03.07.21252647 33758899 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S viral load The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). Teyssou 2021.0 https://doi.org/10.1101/2021.03.21.21253498 10.1101/2021.03.21.21253498 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S viral load The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). Teyssou 2021.0 https://doi.org/10.1101/2021.03.21.21253498 10.1101/2021.03.21.21253498 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S viral load B.1.351 and P.1 samples showed average Ct cycle threshold of 22.2 vs 23 for wildtype (i.e. ~60% higher viral load) comparing 3360 and 22535 samples respectively. Roquebert 2021.0 https://doi.org/10.1101/2021.03.19.21253971 10.1101/2021.03.19.21253971 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28280 D3L YP_009724397.2:p.Asp3Leu N N nucleocapsid phosphoprotein N variant linear antibody epitope effects At the epitope level, the D3L mutation reduces PIWAS signal in 1.5% of COVID patients (outliers reduce from 2.1% in wild type to 0.5% in mutant). In 3 of these patients (0.5% of the population), that alteration represents the strongest antigen signal and substantially reduces the PIWAS antigen score. In the B1.1.7 lineage this is largely counteracted by the S235F mutation, which increases epitope and antigen scores significantly in two individuals, for a net neutral effect at the population level. Haynes 2021.0 https://doi.org/10.1101/2021.01.06.20248960 10.1101/2021.01.06.20248960 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28769 T166A NC_045512.2:g.496A>G YP_009724397.2:p.Thr166Ala N N nucleocapsid phosphoprotein N variant linear antibody epitope effects Confers a significant PIWAS value decrease (reduced antigenicity) Haynes 2020.0 https://doi.org/10.1101/2020.11.23.20235002 10.1101/2020.11.23.20235002 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28144 L84S NC_045512.2:g.251T>C YP_009724396.1:p.Leu84Ser ORF8 ORF8 ORF8 protein ORF8 anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021.0 https://doi.org/10.1101/2021.01.19.21249592 10.1101/2021.01.19.21249592 33501468 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28280 D3L YP_009724397.2:p.Asp3Leu N N nucleocapsid phosphoprotein N subgenomic RNA expression A noncanonical subgenomic RNA which could represent ORF9b is significantly enriched (~16x) in B.1.1.7 SARS-CoV-2 infections, potentially as a result of a triple nucleotide mutation leading to amino acid substitution D3L in nucleocapsid in this lineage which increases complementarity with the genomic leader sequence. Parker 2021.0 https://doi.org/10.1101/2021.03.02.433156 10.1101/2021.03.02.433156 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S antibody epitope effects No detectable fold drop in IC50 of P5A-1D2. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28877 G204R YP_009724397.2:p.Gly204Arg N N nucleocapsid phosphoprotein N subgenomic RNA expression This variant, likely arisen by homologous recombination from the core sequence (CS) of the leader transcription-regulating sequence (TRS), generate a novel sub-genomic RNA transcript for the C-terminal dimerization domain. It may also have increased expression of sub-genomic RNA from other open reading frames, based on public data analysis. Leary 2021.0 https://doi.org/10.1101/2020.04.10.029454 10.1101/2020.04.10.029454 33880475 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28877 G204R YP_009724397.2:p.Gly204Arg N N nucleocapsid phosphoprotein N subgenomic RNA expression This variant, likely arisen by homologous recombination from the core sequence (CS) of the leader transcription-regulating sequence (TRS), generate a novel sub-genomic RNA transcript for the C-terminal dimerization domain. It may also have increased expression of sub-genomic RNA from other open reading frames, based on public data analysis. Leary 2021.0 https://doi.org/10.1101/2020.04.10.029454 10.1101/2020.04.10.029454 33880475 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28877 G204R YP_009724397.2:p.Gly204Arg N N nucleocapsid phosphoprotein N subgenomic RNA expression This variant shows a significant increase in viral load compared to wild type, but not relative to D614G viruses without the variant in circulating viruses in the Spring of 2020 in Saudia Arabia. Mourier 2021.0 https://doi.org/10.1101/2021.05.06.21256706 10.1101/2021.05.06.21256706 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28877 G204R YP_009724397.2:p.Gly204Arg N N nucleocapsid phosphoprotein N gene expression increase By Western blot, a statistically significant 2x increase in N protein expression in packaging cells was observed using mutant novel virus-like-particles. This did not correlate with luciferase activity (which was not statistically different from D614G wild type). Syed 2021.0 https://doi.org/10.1101/2021.08.05.455082 10.1101/2021.08.05.455082 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25855 D155Y NC_045512.2:g.463G>T YP_009724391.1:p.Asp155Tyr ORF3a ORF3a ORF3a protein ORF3a caveolin binding In silico, this mutation is the only one weakening ORF3a's binding affinity for caveolin-1 (essential for entry and endomembrane trafficking of SARS-CoV-2). This mutation is a widespread homoplasy in 20A and 20B lineages. Gupta 2021.0 https://doi.org/10.1101/2021.03.26.437194 10.1101/2021.03.26.437194 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26528,26528,26528 A2A,A2A,A2A NC_045512.2:g.6A>T,NC_045512.2:g.6A>G,NC_045512.2:g.6A>C YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala ,, M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (25x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526 A2S NC_045512.2:g.4G>T YP_009724393.1:p.Ala2Ser M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (38x overrepresentation vs expected count of ~334 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26620 C33S NC_045512.2:g.98G>C YP_009724393.1:p.Cys33Ser M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~32 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26530 D3G NC_045512.2:g.8A>G YP_009724393.1:p.Asp3Gly M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (31x overrepresentation vs expected count of ~53 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S antibody epitope effects No detectable fold drop in IC50 of P5A-1D2. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526,26527,26529 D3H,D3H,D3H NC_045512.2:g.7G>C,NC_045512.2:g.7G>C,NC_045512.2:g.7G>C YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His ,, M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (227x overrepresentation vs expected count of ~14 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27147 D209H NC_045512.2:g.625G>C YP_009724393.1:p.Asp209His M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (81x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26927 E135E NC_045512.2:g.405A>G YP_009724393.1:p.Glu135Glu M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (232x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27021 E167Q NC_045512.2:g.499G>C YP_009724393.1:p.Glu167Gln M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26681 F53F NC_045512.2:g.159C>T YP_009724393.1:p.Phe53Phe M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (163x overrepresentation vs expected count of ~567 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26855,26858 F112F,F112F NC_045512.2:g.336C>T,NC_045512.2:g.336C>T YP_009724393.1:p.Phe112Phe,YP_009724393.1:p.Phe112Phe , M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~463 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26966 H148H NC_045512.2:g.444T>C YP_009724393.1:p.His148His M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26987 H155H NC_045512.2:g.465T>C YP_009724393.1:p.His155His M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26985 H155N NC_045512.2:g.463C>A YP_009724393.1:p.His155Asn M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26895 H125Y NC_045512.2:g.373C>T YP_009724393.1:p.His125Tyr M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (22x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26546 I8I NC_045512.2:g.24T>C YP_009724393.1:p.Ile8Ile M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~80 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26748 I76L NC_045512.2:g.226A>C YP_009724393.1:p.Ile76Leu M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~9 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26749 I76T NC_045512.2:g.227T>C YP_009724393.1:p.Ile76Thr M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (19x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26767 I82T NC_045512.2:g.245T>C YP_009724393.1:p.Ile82Thr M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (67x overrepresentation vs expected count of ~42 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26748 I76V NC_045512.2:g.226A>G YP_009724393.1:p.Ile76Val M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26801,26801,26801 L93L,L93L,L93L NC_045512.2:g.279C>A,NC_045512.2:g.279C>T,NC_045512.2:g.279C>G YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu ,, M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~628 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26882,26882 L120L,L120L NC_045512.2:g.360C>A,NC_045512.2:g.360C>T YP_009724393.1:p.Leu120Leu,YP_009724393.1:p.Leu120Leu , M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26894,26894 L124L,L124L NC_045512.2:g.372C>G,NC_045512.2:g.372C>T YP_009724393.1:p.Leu124Leu,YP_009724393.1:p.Leu124Leu , M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26907,26909,26909 L129L,L129L,L129L NC_045512.2:g.385C>T,NC_045512.2:g.387G>A,NC_045512.2:g.387G>T YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu ,, M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26645 N41N NC_045512.2:g.123C>T YP_009724393.1:p.Asn41Asn M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (19x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26861 N113N NC_045512.2:g.339T>C YP_009724393.1:p.Asn113Asn M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (57x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26873 N117N NC_045512.2:g.351C>T YP_009724393.1:p.Asn117Asn M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27143 N207N NC_045512.2:g.621C>T YP_009724393.1:p.Asn207Asn M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26573,26573,26576,26576,26577,26577 Q19E,Q19E,Q19E,Q19E,Q19E,Q19E NC_045512.2:g.55C>G,,NC_045512.2:g.55C>G,,,NC_045512.2:g.55C>G YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu ,,,,, M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~8 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26972 R150R NC_045512.2:g.450T>C YP_009724393.1:p.Arg150Arg M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~89 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27112 S197T NC_045512.2:g.590G>C YP_009724393.1:p.Ser197Thr M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (18x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27035,27038 T172T,T172T NC_045512.2:g.516A>G,NC_045512.2:g.516A>G YP_009724393.1:p.Thr172Thr,YP_009724393.1:p.Thr172Thr , M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26730 V70L NC_045512.2:g.208G>C YP_009724393.1:p.Val70Leu M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26951,26951,26951 V143V,V143V,V143V NC_045512.2:g.429G>A,NC_045512.2:g.429G>T,NC_045512.2:g.429G>C YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val ,, M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~508 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27059 Y179Y NC_045512.2:g.537C>T YP_009724393.1:p.Tyr179Tyr M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27134 Y204Y NC_045512.2:g.612T>C YP_009724393.1:p.Tyr204Tyr M M membrane glycoprotein M frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023.0 https://doi.org/10.1101/2023.01.30.526314 10.1101/2023.01.30.526314 36778462 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S ACE2 host variant dependency This mutation's measured interaction affinity with ACE2:p.S19P (0.03% minor allele frequency, found almost exclusively in African/African-Americans in the GnomAD database) was significantly lower than the predicted value, indicating that these mutations were not independent. This is consistent with the fact that the ACE2 residue S19 is adjacent to RBD residue S477 in the contact interface. Barton 2021.0 https://doi.org/10.1101/2021.05.18.444646 10.1101/2021.05.18.444646 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22573,22574,22576,22577,22597,22597,22599,22599,22660,22660,22661,22663,22663,22664,22664,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22784,22785,22786,22786,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22938,22939,22939,22942,22942,22942,22992,23009,23010,23012,23013,23018,23027,23029,23029,23030,23031,23031,23053,23053,23054,23054,23055,23055,22992,22995,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075 G339H,G339H,G339H,G339H,R346T,R346T,R346T,R346T,L368I,L368I,L368I,L368I,L368I,L368I,L368I,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,N460K,N460K,N460K,N460K,N460K,N460K,S477N,E484A,E484A,E484A,E484A,F486P,F490S,F490S,F490S,F490S,F490S,F490S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,T478K,T478K,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H ,,,,,NC_045512.2:g.1037G>C,,NC_045512.2:g.1037G>C,NC_045512.2:g.1102C>A,,NC_045512.2:g.1102C>A,,NC_045512.2:g.1102C>A,,NC_045512.2:g.1102C>A,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1380T>A,,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,,NC_045512.2:g.1380T>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity The hACE2-binding affinity of XBB.1.5 RBD has a dissociation constant KD of 3.4 nM, where S486P is the distinguishing Spike mutation vs parent XBB.1 RBD with a much weaker KD (19 nM), as measured by surface plasmon resonance (SPR) assays. Yue 2023.0 https://doi.org/10.1101/2023.01.03.522427 10.1101/2023.01.03.522427 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S antibody epitope effects No detectable fold drop in IC50 of P5A-3C8. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM for binding to the Alpha B1.1.7. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022.0 https://doi.org/10.1101/2022.06.23.497326 10.1101/2022.06.23.497326 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg ,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 507 pM for binding to the Delta B.1.617.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022.0 https://doi.org/10.1101/2022.06.23.497326 10.1101/2022.06.23.497326 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 73 pM for binding to the Omicron B.1.1.529. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022.0 https://doi.org/10.1101/2022.06.23.497326 10.1101/2022.06.23.497326 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21641,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22784,22785,22786,22786,22671,22672,22672,22673,22674,22679,22679,22686,22992,21594,21603,21603,21614,21617,21617,21618,21618,22992,22995,22194,22197,22198,22198,22199,22200,23071,23071,23074,23074,23075,23075 A27S,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,R408S,R408S,R408S,R408S,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T478K,T478K,V213G,V213G,V213G,V213G,V213G,V213G,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H NC_045512.2:g.79G>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 78fM for binding to the Omicron BA.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022.0 https://doi.org/10.1101/2022.06.23.497326 10.1101/2022.06.23.497326 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P22A-1D1. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P22A-1D1. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S antibody epitope effects No detectable fold drop in IC50 of P5A-3C8. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P5A-1D2. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P5A-1D2. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Causes 36.9 fold decrease in KD value for antibody binding of P5A-3C8. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S ACE2 receptor binding affinity Causes 57.1 fold decrease in KD value for antibody binding of P5A-3C8. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Riou 2021.0 https://doi.org/10.1126/scitranslmed.abj6824 10.1126/scitranslmed.abj6824 34931886 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Causes 7.5 fold decrease in KD value for antibody binding of P2C-1F11. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S ACE2 receptor binding affinity Causes 2.9 fold decrease in KD value for antibody binding of P2C-1F11. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Causes 1.5 fold decrease in KD value of antibody binding of ACE2. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S ACE2 receptor binding affinity Causes 1.1 fold decrease in KD value of antibody binding of ACE2. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S ACE2 receptor binding affinity In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed striking resistance with only 38% neutralization at the highest concentration tested. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp S S surface glycoprotein S ACE2 receptor binding affinity In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed a ~4x drop in sensitivity. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity The N501Y mutation had the biggest effect on ACE2 affinity of any VOC mutation tested, increasing the affinity ~10 fold to KD ~7 nM, by increasing the k(on) ~1.8 fold and decreasing the k(off) by ~ 7 fold as measured by surface plasmon resonance. Barton 2021.0 https://doi.org/10.1101/2021.05.18.444646 10.1101/2021.05.18.444646 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.51x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a slight decrease in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23060,23062,23062,23063,23063 D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.52x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis). Compare to full Spike variant complements for major lineages containing this variant subset: 5.43x (B.1.1.7 aka Alpha), 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23271 D614G,D614G,D614G,D614G,D614G,D614G,A570D NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.18x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23604,23604 D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x decrease in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23709 D614G,D614G,D614G,D614G,D614G,D614G,T716I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.12x decrease in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24506 D614G,D614G,D614G,D614G,D614G,D614G,S982A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.3x decrease in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24914 D614G,D614G,D614G,D614G,D614G,D614G,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.1.7 aka Alpha) had 5.43x increased binding relative to D614G alone. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614 D614G,D614G,D614G,D614G,D614G,D614G,L18F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.07x decrease in binding (KD) relative to D614G. Compare to increased binding in full Spike variant complements for major lineages containing this variant subset: 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma). Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21801 D614G,D614G,D614G,D614G,D614G,D614G,D80A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination showed no change relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22206 D614G,D614G,D614G,D614G,D614G,D614G,D215G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.19x increase in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S antibody epitope effects 1.1 fold drop in IC50 of P2C-1F11. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.35x decrease in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22811,22812,22813,22813,22813 D614G,D614G,D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23011,23012 D614G,D614G,D614G,D614G,D614G,D614G,E484K,E484K NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys ,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity This variant appears twice in the experiments, with slightly different affinities (both ~1.2x decrease in binding relative to D614G) using flow cytometry and ACE2 ectodomains-Fc portion IgG complex. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23664 D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed essentially no change in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614,21801,23060,23062,23062,23063,23063,22206,22811,22812,22813,22813,22813,23011,23012,23664 D614G,D614G,D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.351 aka Beta) showed a 3.56x increase in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21621 D614G,D614G,D614G,D614G,D614G,D614G,T20N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.96x increase in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21638 D614G,D614G,D614G,D614G,D614G,D614G,P26S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.58x increase in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21974 D614G,D614G,D614G,D614G,D614G,D614G,D138Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.32x increase in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22132 D614G,D614G,D614G,D614G,D614G,D614G,R190S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.82x increase in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S antibody epitope effects 2.6 fold increase in IC50 of P2C-1F11. Zhang 2021.0 https://doi.org/10.1038/s41467-021-24514-w 10.1038/s41467-021-24514-w 34244522 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22812,22812 D614G,D614G,D614G,D614G,D614G,D614G,K417T,K417T NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1250A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr ,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.28x increase in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525 D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.21x increase in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24642 D614G,D614G,D614G,D614G,D614G,D614G,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.69x decrease in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642 D614G,D614G,D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing P.1 aka Gamma) showed a 4.24x increase in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21575 D614G,D614G,D614G,D614G,D614G,D614G,L5F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.1x decrease in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21846 D614G,D614G,D614G,D614G,D614G,D614G,T95I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x decrease in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D614G,D614G,D253G,D253G,D253G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly ,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.08x decrease in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21575,21846,22317,22319,22320,23011,23012,23664 D614G,D614G,D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.526) showed a 1.78x increase in binding (KD) relative to D614G, even though each variant independently decreases binding. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21600 D614G,D614G,D614G,D614G,D614G,D614G,S13I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.42x increase in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22018 D614G,D614G,D614G,D614G,D614G,D614G,W152C NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x increase in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S antibody epitope effects Highly resistant to mAb SARS2-32 of 10 antibodies tested. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.66x increase in binding (KD) relative to D614G. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21600,22018,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.429 aka Epsilon) showed a 2.82x increase in binding (KD) relative to D614G, indicating a strong marginal effect for L452R. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617) showed a 1.85x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.1) showed a 1.12x increase in binding (KD) relative to D614G, but described as ""not significant"". [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.2 aka Delta) showed a 2.34x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity In the case of VOC B.1.1.7+E484K, the addition of the E484K mutation to N501Y further increased the affinity, to ~15 fold higher than WT RBD (KD ~5 nM), by further increasing the k(on) as measured by surface plasmon resonance. Because the higher k(on) could result in mass transfer limiting binding, we confirmed that the kinetic measurement for this variant was not substantially affected by varying levels of immobilization. Barton 2021.0 https://doi.org/10.1101/2021.05.18.444646 10.1101/2021.05.18.444646 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr , S S surface glycoprotein S ACE2 receptor binding affinity The K417T mutation decreased the affinity ~2 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance. Barton 2021.0 https://doi.org/10.1101/2021.05.18.444646 10.1101/2021.05.18.444646 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S ACE2 receptor binding affinity The K417N mutation decreased the affinity ~4 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance. Barton 2021.0 https://doi.org/10.1101/2021.05.18.444646 10.1101/2021.05.18.444646 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity The affinity of the B.1.351 RBD variants for ACE2 increased by 3.7 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants. Barton 2021.0 https://doi.org/10.1101/2021.05.18.444646 10.1101/2021.05.18.444646 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812,23011,23012,23060,23062,23062,23063,23063 K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity The affinity of the P.1 RBD variants for ACE2 increased by 5.3 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants. Barton 2021.0 https://doi.org/10.1101/2021.05.18.444646 10.1101/2021.05.18.444646 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity The KD for the pseudotyped P.1-ACE2 interaction is 4.8 nM, showing that binding to P.1 is essentially indistinguishable from B.1.351 (4.0 nM), which binds with ~19x greater affinity that wild type. Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.1.7. We observed a dramatic increase (relative to D614G) in binding of soluble ACE2 to B.1.1.7, and to a lesser extent to B.1.351, which both carry the N501Y mutation (see Fig 3). Planas 2021.0 https://doi.org/10.1038/s41591-021-01318-5 10.1038/s41591-021-01318-5 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.351. We observed an increase (relative to D614G) in binding of soluble ACE2 to B.1.351, and to a much gearter extent to B.1.1.7, which both carry the N501Y mutation (see Fig 3). Planas 2021.0 https://doi.org/10.1038/s41591-021-01318-5 10.1038/s41591-021-01318-5 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His ,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells for ACE2 affinity changes vs D614G alone, showing a ~70% drop in IC50 (i.e. increased affinity). Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity ~4-fold increase in binding affinity vs wild type. Motozono 2021.0 https://doi.org/10.1101/2021.04.02.438288 10.1101/2021.04.02.438288 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity ~4-fold increase in binding affinity vs wild type. Motozono 2021.0 https://doi.org/10.1101/2021.04.02.438288 10.1101/2021.04.02.438288 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity In silico methods (PyMOL and PDBePISA) involving mutagenesis (N501Y mutation) and interface analysis focusing on the Spike RDB-ACE2 interaction showed that the SARS-CoV-2 N501Y mutant (lineage B.1.1.7) establishes a more significant number of interactions relating to the mutant residue Y501 (Spike RDB) with residues Y41 and K353 (ACE2). This finding shows that the increased infectivity of SARS-CoV-2 lineage B.1.1.7 is associated with the interaction force between the Spike RBD Y501 mutant residue with the ACE2 receptor, which in this strain is increased. 2021.0 https://doi.org/10.1101/2020.12.29.424708 10.1101/2020.12.29.424708 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23103 S477N,S514F NC_045512.2:g.1430G>A,NC_045512.2:g.1541C>T YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Ser514Phe , S S surface glycoprotein S antibody epitope effects Highly resistant to mAbs SARS2-07 and SARS2-16 of 10 antibodies tested. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity This mutation combination causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala S S surface glycoprotein S ACE2 receptor binding affinity This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S ACE2 receptor binding affinity ~4-fold increase in binding affinity vs wild type. Motozono 2021.0 https://doi.org/10.1101/2021.04.02.438288 10.1101/2021.04.02.438288 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S ACE2 receptor binding affinity ~1.7-fold increase in binding affinity vs wild type. Motozono 2021.0 https://doi.org/10.1101/2021.04.02.438288 10.1101/2021.04.02.438288 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity The B.1.351 variant constellation causes an ∼20-fold increase in affinity for ACE2 compared with Wuhan RBD, which may influence transmissibility. Zhou 2021.0 https://doi.org/10.1016/j.cell.2021.02.037 10.1016/j.cell.2021.02.037 33730597 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Pseudotype lentivirus for the full B.1.351 Spike variant list shows increase affinity for ACE2 as measured by IC50. This is in contrast to B.1.1.7 which showed no major change, indicating that the shared N501Y mutation is the driver of affinity change, attentuated in the B.1.1.7 mutatioon set, but maintained in the B.1.351 lineage. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro S S surface glycoprotein S ACE2 receptor binding affinity Using molecular dynamic simulation, the mildly (~1kcal/mol) enhanced binding energy of this variant is primarily contributed by Tyr505 (−4.98 kcal/mol) which is now involved in a strong hydrogen bonding network with Arg393. Another important energetic contribution comes from the altered orientation of Tyr41 which is now involved with two hydrogen-bonding interactions with Asp355 and Thr500. 2021.0 https://doi.org/10.1016/j.bbrc.2021.01.035 10.1016/j.bbrc.2021.01.035 33602511 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant. Collier 2021.0 https://doi.org/10.1038/s41586-021-03412-7 10.1038/s41586-021-03412-7 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant. Collier 2021.0 https://doi.org/10.1038/s41586-021-03412-7 10.1038/s41586-021-03412-7 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro S S surface glycoprotein S antibody epitope effects Highly resistant to mAb SARS2-01 of 10 antibodies tested. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021.0 https://doi.org/10.1101/2021.02.16.431305 10.1101/2021.02.16.431305 33619479 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021.0 https://doi.org/10.1101/2021.02.16.431305 10.1101/2021.02.16.431305 33619479 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021.0 https://doi.org/10.1101/2021.02.14.431117 10.1101/2021.02.14.431117 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021.0 https://doi.org/10.1101/2021.02.16.431305 10.1101/2021.02.16.431305 33619479 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021.0 https://doi.org/10.1101/2021.02.14.431117 10.1101/2021.02.14.431117 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021.0 https://doi.org/10.1101/2021.03.04.433887 10.1101/2021.03.04.433887 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021.0 https://doi.org/10.1101/2021.02.16.431305 10.1101/2021.02.16.431305 33619479 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021.0 https://doi.org/10.1101/2021.02.14.431117 10.1101/2021.02.14.431117 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021.0 https://doi.org/10.1101/2021.03.04.433887 10.1101/2021.03.04.433887 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y. Laffeber 2021.0 https://doi.org/10.1101/2021.02.22.432357 10.1101/2021.02.22.432357 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021.0 https://doi.org/10.1101/2021.02.16.431305 10.1101/2021.02.16.431305 33619479 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021.0 https://doi.org/10.1101/2021.02.14.431117 10.1101/2021.02.14.431117 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021.0 https://doi.org/10.1101/2021.03.04.433887 10.1101/2021.03.04.433887 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y. Laffeber 2021.0 https://doi.org/10.1101/2021.02.22.432357 10.1101/2021.02.22.432357 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM). Ramanathan 2021.0 https://doi.org/10.1101/2021.02.22.432359 10.1101/2021.02.22.432359 33655251 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021.0 https://doi.org/10.1101/2021.02.16.431305 10.1101/2021.02.16.431305 33619479 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021.0 https://doi.org/10.1101/2021.02.14.431117 10.1101/2021.02.14.431117 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021.0 https://doi.org/10.1101/2021.03.04.433887 10.1101/2021.03.04.433887 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y. Laffeber 2021.0 https://doi.org/10.1101/2021.02.22.432357 10.1101/2021.02.22.432357 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM). Ramanathan 2021.0 https://doi.org/10.1101/2021.02.22.432359 10.1101/2021.02.22.432359 33655251 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity This combination showed ~3x increase binding to ACE2 vs wild type, about half that of the B.1.1.7 lineage, suggesting that the K417N mutation is slightly detrimental to ACE2 binding, probably as a result of disrupting the salt bridge formed with ACE2 residue D30 Collier 2021.0 https://doi.org/10.1038/s41586-021-03412-7 10.1038/s41586-021-03412-7 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported 3-fold decrease in affinity compared to wild-type RBD on the cell surface (Kd = 145.1nM vs 56.9nM). Tian 2021.0 https://doi.org/10.1101/2021.02.14.431117 10.1101/2021.02.14.431117 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S ACE2 receptor binding affinity Reported moderate increase in affinity compared to wild-type RBD on the cell surface (Kd = 38.5nM vs 56.9nM). Tian 2021.0 https://doi.org/10.1101/2021.02.14.431117 10.1101/2021.02.14.431117 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S ACE2 receptor binding affinity In four cell lines (including 293T-hACE2 cells), this mutation combination increases infectivity vs D614G alone Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.25 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S antibody epitope effects Highly resistant to mAbs SARS2-07, SARS2-19, 1B07, SARS2-16 and 2B04 of 10 antibodies tested. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021.0 https://doi.org/10.1101/2021.02.02.428884 10.1101/2021.02.02.428884 33564771 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021.0 https://doi.org/10.1101/2021.02.02.428884 10.1101/2021.02.02.428884 33564771 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021.0 https://doi.org/10.1101/2021.02.14.431117 10.1101/2021.02.14.431117 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021.0 https://doi.org/10.1101/2021.02.02.428884 10.1101/2021.02.02.428884 33564771 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021.0 https://doi.org/10.1101/2021.02.14.431117 10.1101/2021.02.14.431117 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity. Zhu 2021.0 https://doi.org/10.1101/2021.01.11.426269 10.1101/2021.01.11.426269 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021.0 https://doi.org/10.1101/2021.02.02.428884 10.1101/2021.02.02.428884 33564771 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021.0 https://doi.org/10.1101/2021.02.14.431117 10.1101/2021.02.14.431117 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity. Zhu 2021.0 https://doi.org/10.1101/2021.01.11.426269 10.1101/2021.01.11.426269 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM). Ramanathan 2021.0 https://doi.org/10.1101/2021.02.22.432359 10.1101/2021.02.22.432359 33655251 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S antibody epitope effects Highly resistant to mAbs SARS2-01, 1B07, SARS2-32, SARS2-35 and SARS2-07 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021.0 https://doi.org/10.1101/2021.02.02.428884 10.1101/2021.02.02.428884 33564771 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021.0 https://doi.org/10.1101/2021.02.14.431117 10.1101/2021.02.14.431117 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity. Zhu 2021.0 https://doi.org/10.1101/2021.01.11.426269 10.1101/2021.01.11.426269 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM). Ramanathan 2021.0 https://doi.org/10.1101/2021.02.22.432359 10.1101/2021.02.22.432359 33655251 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S ACE2 receptor binding affinity The most frequent RBM mutation N501Y (165,519 instances) makes defective the atypical N-glycosylation sequon NGV 501-503, becoming a key RBM position for the interaction with hACE2-binding hotspot 353. Gamez 2021.0 https://doi.org/10.1101/2021.04.09.439154 10.1101/2021.04.09.439154 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23003 N481Y NC_045512.2:g.1441A>T YP_009724390.1:p.Asn481Tyr S S surface glycoprotein S ACE2 receptor binding affinity Minor variant in initial round of in vitro evolution experiment for ACE2 binding. Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro S S surface glycoprotein S ACE2 receptor binding affinity Minor variant selected in late rounds of an in vitro evolution experiment for ACE2 binding. Shown to increase the thermostability but decrease the association rate constant of the RBD to ACE2 Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23012 E484R,E484R , YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg , S S surface glycoprotein S ACE2 receptor binding affinity This is a two point mutation change giving this position the highest possible fitness, has higher affinity than circulating E484K variant. Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23012 E484R,E484R , YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg , S S surface glycoprotein S ACE2 receptor binding affinity This is a two point mutation change giving this position the highest possible fitness, has higher affinity than circulating E484K variant. Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23012 E484R,E484R , YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg , S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.15 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-02, 1B07, SARS2-16, SARS2-32, SARS2-35 and 2B04 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K NC_045512.2:g.1380T>A,,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys ,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K NC_045512.2:g.1380T>A,,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys ,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K NC_045512.2:g.1380T>A,,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys ,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.09 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063 E484K,E484K,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063 Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. The extent of affinity increase with Q498R and N501Y is not exactly quantified, as E484K always emerged with this duo during in vitro evolution. Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.07 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>C,NC_045512.2:g.531G>T,NC_045512.2:g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile ,, S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917 L452Q NC_045512.2:g.1355T>A YP_009724390.1:p.Leu452Gln S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.07 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp ,, S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22597,22599,22599 R346T,R346T,R346T,R346T ,NC_045512.2:g.1037G>C,,NC_045512.2:g.1037G>C YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr ,,, S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912,22912,22916 L452M,L452M,L452M NC_045512.2:g.1354C>A,,NC_045512.2:g.1354C>A YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met ,, S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn , S S surface glycoprotein S antibody epitope effects Highly resistant to mAb SARS2-01 and moderately resistant to 2H04 of 10 antibodies tested. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S ACE2 receptor binding affinity Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility. Singh 2021.0 https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S ACE2 receptor binding affinity Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility. Singh 2021.0 https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding, with increasing proportion in subsequent rounds. Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22905 N448S NC_045512.2:g.1343A>G YP_009724390.1:p.Asn448Ser S S surface glycoprotein S ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22964 I468V NC_045512.2:g.1402A>G YP_009724390.1:p.Ile468Val S S surface glycoprotein S ACE2 receptor binding affinity Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding. Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp S S surface glycoprotein S antibody epitope effects Highly resistant to mAbs SARS2-02, SARS2-32 and SARS2-35 of 10 antibodies tested. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009 V483L NC_045512.2:g.1447G>C YP_009724390.1:p.Val483Leu S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S ACE2 receptor binding affinity Among the first selected variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S ACE2 receptor binding affinity Among the first selected variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr S S surface glycoprotein S ACE2 receptor binding affinity Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding. Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr S S surface glycoprotein S ACE2 receptor binding affinity Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding. Zahradnik 2021.0 https://doi.org/10.1101/2021.01.06.425392 10.1101/2021.01.06.425392 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr S S surface glycoprotein S ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020.0 https://doi.org/10.1016/j.cell.2020.08.012 10.1016/j.cell.2020.08.012 32841599 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S vaccinee plasma binding 1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S vaccinee plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23060,23062,23062,23063,23063 D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23271 D614G,D614G,D614G,D614G,D614G,D614G,A570D NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp ,,,,,, S S surface glycoprotein S vaccinee plasma binding No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23604,23604 D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp , S S surface glycoprotein S antibody epitope effects Highly resistant to mAb SARS2-07 nd moderately resistant to SARS2-16 of 10 antibodies tested. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23709 D614G,D614G,D614G,D614G,D614G,D614G,T716I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24506 D614G,D614G,D614G,D614G,D614G,D614G,S982A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala ,,,,,, S S surface glycoprotein S vaccinee plasma binding 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24914 D614G,D614G,D614G,D614G,D614G,D614G,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccinee plasma binding This variant combination (representing B.1.1.7 aka Alpha) showed no change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.28x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614 D614G,D614G,D614G,D614G,D614G,D614G,L18F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.30x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.28x increase (B.1.351 aka Beta), and 1.14x decrease (P.1 aka Gamma). 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.17x increase (B.1.351 aka Beta), and 1.47x decrease (P.1 aka Gamma). Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21801 D614G,D614G,D614G,D614G,D614G,D614G,D80A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.64x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.35x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22206 D614G,D614G,D614G,D614G,D614G,D614G,D215G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.79x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S vaccinee plasma binding 1.43x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S vaccinee plasma binding 1.05x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.45x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22811,22812,22813,22813,22813 D614G,D614G,D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,,,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.76x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.75x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys S S surface glycoprotein S antibody epitope effects Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23011,23012 D614G,D614G,D614G,D614G,D614G,D614G,E484K,E484K NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys ,,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23664 D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614,21801,23060,23062,23062,23063,23063,22206,22811,22812,22813,22813,22813,23011,23012,23664 D614G,D614G,D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccinee plasma binding This variant combination (representing B.1.351 aka Beta) showed a 1.28x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. It shows a 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21621 D614G,D614G,D614G,D614G,D614G,D614G,T20N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.39x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21638 D614G,D614G,D614G,D614G,D614G,D614G,P26S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.23x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21974 D614G,D614G,D614G,D614G,D614G,D614G,D138Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22132 D614G,D614G,D614G,D614G,D614G,D614G,R190S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.59x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22812,22812 D614G,D614G,D614G,D614G,D614G,D614G,K417T,K417T NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1250A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr ,,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525 D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24642 D614G,D614G,D614G,D614G,D614G,D614G,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.22x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr , S S surface glycoprotein S antibody epitope effects Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642 D614G,D614G,D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccinee plasma binding This variant combination (representing P.1 aka Gamma) showed a 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21575 D614G,D614G,D614G,D614G,D614G,D614G,L5F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.23x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21846 D614G,D614G,D614G,D614G,D614G,D614G,T95I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D614G,D614G,D253G,D253G,D253G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly ,,,,,,,, S S surface glycoprotein S vaccinee plasma binding No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21575,21846,22317,22319,22320,23011,23012,23664 D614G,D614G,D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccinee plasma binding This variant combination (representing lineage B.1.526) showed a 1.34x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21600 D614G,D614G,D614G,D614G,D614G,D614G,S13I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22018 D614G,D614G,D614G,D614G,D614G,D614G,W152C NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys ,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.03x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,,,,,, S S surface glycoprotein S vaccinee plasma binding 1.05x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.16x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21600,22018,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,,,,,,,, S S surface glycoprotein S vaccinee plasma binding This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. [Stark contrast to 2.15x increase in binding by convalescent plasma 8 months post infection, presumably via memory B cell affinity maturation against L452R effects] 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S vaccinee plasma binding This variant combination (representing lineage B.1.617) showed a 1.30x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.18x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-02 and SARS2-32 of 10 antibodies tested. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccinee plasma binding This variant combination (representing lineage B.1.617.1) showed a 1.79x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccinee plasma binding This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.89x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>C,NC_045512.2:g.531G>T,NC_045512.2:g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile ,, S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*16:01. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-07, SARS2-16 and SARS2-19 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24130 N856K NC_045512.2:g.2568C>A YP_009724390.1:p.Asn856Lys S S surface glycoprotein S branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. Lucaci 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp ,,,,,,,,,,,,,,, S S surface glycoprotein S branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. [PG: This mutation is adjacent to a well known deletion, which may confound the significance of this variant] Lucaci 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22686 S375F NC_045512.2:g.1124C>T YP_009724390.1:p.Ser375Phe S S surface glycoprotein S branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. Lucaci 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S humoral response durability In a prospective study of 107 hospitalized patients, decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7 and P.1 variants for at least 6 months (last of two samples taken) in patients previously hospitalized for COVID-19. A weaker protection was however observed for the B.1.351 variant. Betton 2020.0 https://doi.org/10.1093/cid/ciab308 10.1093/cid/ciab308 33851216 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22227,23399,23401,23401,23402,23403,23403 A222V,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S humoral response durability 27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3), i.e. with a 9 month interval. Both cases were mild. No significant differences in the neutralizing capacity of the two lineages were observed in 4 sera taken (1 pre-reinfection, three post-reinfection). Neutralizing antibody titres (IC50) before and immediately after re-infection were <300 against both strains, and jumped >7x upon re-infection. Viral titres were also higher in the second case. Second case also includes N:p.A220V Brehm 2021.0 https://doi.org/10.3390/v13040661 10.3390/v13040661 33921216 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S clinical indicators After adjusting for the age factor, in a prospective Chinese cohort study B.1.1.7 variant infection (compared to B.1.140) was the risk factor for C-reactive protein (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), Serum amyloid A (0.011, 5.031, [1.459, 17.354]), Creatine Kinase (0.034, 4.34, [0.05, 0.91]), CD4+ T lymphocyte (0.029, 3.31, [1.13, 9.71]), and Ground Glass Opacity (0.005, 5.418, [1.656, 17.729]) Song 2021.0 https://doi.org/10.1101/2021.05.04.21256655 10.1101/2021.05.04.21256655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking Modelling the Delta variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increased 11x relative to wild type (15.3 vs 1.4). [del ~157 truncated due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a coinfection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant. Liu 2021.0 https://doi.org/10.1101/2021.08.12.456173v3 10.1101/2021.08.12.456173v3 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking Modelling the Alpha variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 3.9x relative to wild type (5.4 vs 1.4). This is less efficient than Delta (11x vs wildtype using a P681R mutation instead). [del ~144 changed due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a co-infection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant. Liu 2021.0 https://doi.org/10.1101/2021.08.12.456173v3 10.1101/2021.08.12.456173v3 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S trafficking This mutation alone accounts for most of the increased infectivity of the Alpha variant, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters, and Vero E6 (NHP) and Calu-3 (human) cell lines. Liu 2021.0 https://doi.org/10.1101/2021.03.08.434499 10.1101/2021.03.08.434499 33758836 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021.0 https://doi.org/10.1101/2021.06.10.447999 10.1101/2021.06.10.447999 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S trafficking In the absence of N501Y, this Alpha lineage change in the furin clevage site did NOT show significant increase in infectivity relative to wild type, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters. Liu 2021.0 https://doi.org/10.1101/2021.03.08.434499 10.1101/2021.03.08.434499 33758836 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,D950N NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking In primary human airway epithelial cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 1.9x relative to wild type (2.7 vs 1.4). This is the Delta variant with the P681R furin cleavage site mutation absent. [del ~157 truncated due to ambiguity] Liu 2021.0 https://doi.org/10.1101/2021.08.12.456173v3 10.1101/2021.08.12.456173v3 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23604,23399,23401,23401,23402,23403,23403,23873,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,P681R,D614G,D614G,D614G,D614G,D614G,D614G,A771S,D950N NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2311G>T,NC_045512.2:g.2848G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala771Ser,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking ~4.5x cleavage of S2 relative to WA1 (D614G) wildtype by Delta (B.1.617.2) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~3.5x for closely related Kappa B.1.617.1 also with P681R at the cleavage site). Esclera 2021.0 https://doi.org/10.1101/2021.08.05.455290 10.1101/2021.08.05.455290 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking ~3.5x cleavage of S2 relative to WA1 (D614G) wildtype by Kappa (B.1.617.1) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~4.5x for closely related Delta B.1.617.2 also with P681R at the cleavage site). Esclera 2021.0 https://doi.org/10.1101/2021.08.05.455290 10.1101/2021.08.05.455290 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking ~2.5x cleavage of S2 relative to WA1 (D614G) wildtype by Alpha variant variant as measured by mass spectrometry of Vero-TMPRSS culture. Esclera 2021.0 https://doi.org/10.1101/2021.08.05.455290 10.1101/2021.08.05.455290 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking ~6x cleavage of S2 relative to WA1 (D614G) wildtype by Beta variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but A701V is downstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations. Esclera 2021.0 https://doi.org/10.1101/2021.08.05.455290 10.1101/2021.08.05.455290 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking ~6x cleavage of S2 relative to WA1 (D614G) wildtype by Gamma variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but H655Y is upstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations. Esclera 2021.0 https://doi.org/10.1101/2021.08.05.455290 10.1101/2021.08.05.455290 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23399,23401,23401,23402,23403,23403 P681R,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S trafficking Quantification of the band intensities showed that the P681R mutation, which lies near the proteolytic processing site, caused a small increase in proteolytic processing as measured by a 2-fold decrease in the ratio of S/S2. Tada 2021.0 https://doi.org/10.1101/2021.05.14.444076 10.1101/2021.05.14.444076 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking ~4x more efficient S2 domain cleavage compared to wild type in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23401,23402,23403,23403 P384L,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,, S S surface glycoprotein S trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking ~5x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied] Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S trafficking ~6x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied] Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23401,23402,23403,23403 P384L,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,, S S surface glycoprotein S trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~9x, Vero ~8x, and Calu-3 ~8x. Compare to wild type at ~5x across cell types. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,, S S surface glycoprotein S trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~13x, Vero ~10x, and Calu-3 ~10x. Compare to wild type at ~5x across cell types. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~11x, Vero ~10x, and Calu-3 ~11x. Compare to wild type at ~5x across cell types. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,, S S surface glycoprotein S trafficking 9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23399,23401,23401,23402,23403,23403 E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,, S S surface glycoprotein S trafficking ~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,, S S surface glycoprotein S trafficking ~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking ~9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (no synergy as level approx. that of N501Y alone). Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S trafficking ~12x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of 501 and 484). Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,22811,22812,22813,22813,22813,23399,23401,23401,23402,23403,23403 E484K,E484K,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S trafficking Approximately as infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of the individual variants). Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,22811,22812,22813,22813,22813,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 E484K,E484K,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking ~13x more infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,, S S surface glycoprotein S trafficking 9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021.0 https://doi.org/10.1101/2021.06.10.447999 10.1101/2021.06.10.447999 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln S S surface glycoprotein S trafficking This variant alone shows a 10x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. Ferriera 2021.0 https://doi.org/10.1101/2021.05.08.443253 10.1101/2021.05.08.443253 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S trafficking This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. [listed as L454R in Figure, but L452R in text, also text suggests not statistically significant, but error bars say otherwise in Figure 4] Ferriera 2021.0 https://doi.org/10.1101/2021.05.08.443253 10.1101/2021.05.08.443253 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23011,23012 L452R,L452R,L452R,L452R,L452R,L452R,E484K,E484K ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,,NC_045512.2:g.1450G>A YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys ,,,,,,, S S surface glycoprotein S trafficking This variant combination shows a ~4-5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, same as L452R alone. Ferriera 2021.0 https://doi.org/10.1101/2021.05.08.443253 10.1101/2021.05.08.443253 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S trafficking This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. Ferriera 2021.0 https://doi.org/10.1101/2021.05.08.443253 10.1101/2021.05.08.443253 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23011,23012,23604 L452R,L452R,L452R,L452R,L452R,L452R,E484K,E484K,P681R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg ,,,,,,,, S S surface glycoprotein S trafficking This variant combination shows a ~3x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, significantly less of a decrease than any B.1.617 lineage variants alone, suggesting a synergistic effect on cell entry while maintaining known immunity esacpe mutants. Ferriera 2021.0 https://doi.org/10.1101/2021.05.08.443253 10.1101/2021.05.08.443253 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S trafficking In one of eight cell lines tested (293T lung cells), a modest increase in cell entry was observed. Hoffman 2021.0 https://doi.org/10.1101/2021.05.04.442663 10.1101/2021.05.04.442663 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21624,22022,22216,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24863 R21T,E154K,Q218H,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,H1101D NC_045512.2:g.62G>C,NC_045512.2:g.460G>A,NC_045512.2:g.654G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3301C>G YP_009724390.1:p.Arg21Thr,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Gln218His,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.His1101Asp ,,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking In two of eight cell lines tested (Caco-2 intenstinal and Calu-3 lung), a modest increase in cell entry was observed. This increase was not observed in a Calu-3 cell line with overexpressed ACE2. [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021.0 https://doi.org/10.1101/2021.05.04.442663 10.1101/2021.05.04.442663 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking Live virus was tested ex vivo in reconstituted brochial epithelium, and out competed wild type. Touret 2021.0 https://doi.org/10.1101/2021.03.22.436427 10.1101/2021.03.22.436427 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slightly increased infection rate amongst the cells. [in what is essentially a replicate experiment in the same paper, because each B.1.351 lineage variant was independetly evaluated and N501 is in both lineages, a significant decrease was observed, therefore the error bars described in this paper should be interpreted carefully] Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp S S surface glycoprotein S trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing statistically significant increased infection rate amongst the cells. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing NO statistically significant infection rate change amongst the cells, suggesting that furin cleavage typically used for cell entry is not affected by this change one amino acid upstream of the RXXR recognition pattern. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile S S surface glycoprotein S trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. T716I was expressed at significantly lower level, accounting for the decreased infectivity of this spike protein. This property may be specific to spike protein biosynthesis in 293T cells and is not likely to reflect the situation in vivo given the reported increase in infectivity of the B.1.1.7 virus. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala S S surface glycoprotein S trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (70%) increase in infection rate amongst the cells, hence this individual variant is likely to significantly contribute to cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His S S surface glycoprotein S trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S trafficking Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, moreso than this combination with the addition of P681H. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23604,23604 N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.2042C>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,, S S surface glycoprotein S trafficking Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, but to a smaller extent than N501Y and the deletion alone. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe S S surface glycoprotein S trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggetsing that this mutation does not contributing to cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala S S surface glycoprotein S trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly S S surface glycoprotein S trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23664 A701V NC_045512.2:g.2102C>T YP_009724390.1:p.Ala701Val S S surface glycoprotein S trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking Lentiviral pseudotyped with all key mutations from B.1.351 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting some synergy between the mutations to decrease cell entry fitness (i.e. cell entry is liklely not the driver of this lineage's dominance). Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23401,23402,23403,23403 S477N,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S trafficking Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His ,,,,,,,,,,,, S S surface glycoprotein S trafficking Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920,25249,25249,25249 Y453F,M1229I,M1229I,M1229I NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile ,,, S S surface glycoprotein S trafficking Lentiviral pseudotyped with all key mutations from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (~50%) decrease in infection rate amongst the cells, suggesting that this anthropozoonotic event is driven by other factors at the expense of human cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S trafficking Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S trafficking Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S trafficking Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability. Motozono 2021.0 https://doi.org/10.1101/2021.04.02.438288 10.1101/2021.04.02.438288 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25249,25249,25249 M1229I,M1229I,M1229I NC_045512.2:g.3687G>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile ,, S S surface glycoprotein S trafficking Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, much closer to D614G activity level than Y453F alone, suggesting compensatory effects between the deletion and the mutation in human cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing moderate decrease in infection rate amongst the cells, significantly lower than the deletion or Y453F alone, or their combination, suggesting a synergistic effect on poorer human cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920,25249,25249,25249 Y453F,M1229I,M1229I,M1229I NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile ,,, S S surface glycoprotein S trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells, markedly higher infectivity than either mutation alone, suggesting a synergistic net neutral effect on human cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920,24999,25000 Y453F,S1147L,S1147L NC_045512.2:g.1358A>T,, YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Ser1147Leu,YP_009724390.1:p.Ser1147Leu ,, S S surface glycoprotein S trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild to modest decrease in infection rate amongst the cells, suggesting a net mild negative effect on human cell entry fitness. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S trafficking Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability. Motozono 2021.0 https://doi.org/10.1101/2021.04.02.438288 10.1101/2021.04.02.438288 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>C,NC_045512.2:g.531G>T,NC_045512.2:g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile ,, S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*07:01. de Silva 2021.0 https://doi.org/10.1101/2021.04.08.438904 10.1101/2021.04.08.438904 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S trafficking Increased stability of RBD expression in yeast, suggesting increased Spike protein stability. Motozono 2021.0 https://doi.org/10.1101/2021.04.02.438288 10.1101/2021.04.02.438288 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S trafficking VSV pseudotype B.1.1.7 showed no significant difference in cell entry relative to wild type in 6 cell lines. Cell fusion proficiency was unchanged. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S trafficking VSV pseudotype B.1.351 showed slight decrease in cell entry relative to wild type in 263T-ACE2 (kidney) cell line, and slight increase in Calu-3 (lung). Cell fusion proficiency was slight impaired. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking VSV pseudotype P.1 showed slight decrease in cell entry relative to wild type in 262T and 263T-ACE2 (kidney) cell lines. Cell fusion proficiency was slight impaired. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S trafficking This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). 2021.0 https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S trafficking This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). 2021.0 https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S trafficking While the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC). Lubinski 2021.0 https://doi.org/10.1101/2021.04.06.438731 10.1101/2021.04.06.438731 33851153 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681R NC_045512.2:g.2042C>G YP_009724390.1:p.Pro681Arg S S surface glycoprotein S trafficking This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). [Inference from similar positively charged substitution P681H actually described in the work] 2021.0 https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S trafficking We observed increased entry by pseudoviruses carrying the L452R mutation compared to D614G alone, with a 6.7 to 22.5-fold increase in 293T cells and a 5.8 to 14.7-fold increase in human airway organoids. Deng 2021.0 https://doi.org/10.1101/2021.03.07.21252647 10.1101/2021.03.07.21252647 33758899 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22018 W152C NC_045512.2:g.456G>T YP_009724390.1:p.Trp152Cys S S surface glycoprotein S trafficking Pseudoviruses carrying the W152C mutation demonstrated small increases in cell entry compared to D614G alone in 293T cells and human airway organoids. Deng 2021.0 https://doi.org/10.1101/2021.03.07.21252647 10.1101/2021.03.07.21252647 33758899 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021.0 https://doi.org/10.1101/2021.06.10.447999 10.1101/2021.06.10.447999 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 1 (B.1.1.7) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2. Hu 2021.0 https://doi.org/10.1101/2021.01.22.427749 10.1101/2021.01.22.427749 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,, S S surface glycoprotein S trafficking The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 2 (B.1.351) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2. Hu 2021.0 https://doi.org/10.1101/2021.01.22.427749 10.1101/2021.01.22.427749 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2:g.2492C>T YP_009724390.1:p.Ala831Val S S surface glycoprotein S trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021.0 https://doi.org/10.1101/2021.01.24.428007 10.1101/2021.01.24.428007 33532777 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021.0 https://doi.org/10.1101/2021.01.24.428007 10.1101/2021.01.24.428007 33532777 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021.0 https://doi.org/10.1101/2021.01.24.428007 10.1101/2021.01.24.428007 33532777 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. 2020.0 https://doi.org/10.1038/s41467-020-19808-4 10.1038/s41467-020-19808-4 33243994 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021.0 https://doi.org/10.1101/2021.01.24.428007 10.1101/2021.01.24.428007 33532777 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu S S surface glycoprotein S antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021.0 https://doi.org/10.1101/2021.06.10.447999 10.1101/2021.06.10.447999 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. 2020.0 https://doi.org/10.1038/s41467-020-19808-4 10.1038/s41467-020-19808-4 33243994 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses. Ozono 2020.0 https://doi.org/10.1038/s41467-021-21118-2 10.1038/s41467-021-21118-2 33558493 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021.0 https://doi.org/10.1101/2021.01.24.428007 10.1101/2021.01.24.428007 33532777 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. 2020.0 https://doi.org/10.1038/s41467-020-19808-4 10.1038/s41467-020-19808-4 33243994 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses. Ozono 2020.0 https://doi.org/10.1038/s41467-021-21118-2 10.1038/s41467-021-21118-2 33558493 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S trafficking The increased transduction with Spike D614G ranged from 1.3- to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2 and from 1.5- to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction. Daniloski 2021.0 https://doi.org/10.7554/eLife.65365 10.7554/eLife.65365 33570490 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24077 D839Y NC_045512.2:g.2515G>T YP_009724390.1:p.Asp839Tyr S S surface glycoprotein S trafficking Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry. Barrett 2021.0 https://doi.org/10.1101/2021.01.24.428007 10.1101/2021.01.24.428007 33532777 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24077 D839N NC_045512.2:g.2515G>A YP_009724390.1:p.Asp839Asn S S surface glycoprotein S trafficking Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry. Barrett 2021.0 https://doi.org/10.1101/2021.01.24.428007 10.1101/2021.01.24.428007 33532777 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25350 P1263L NC_045512.2:g.3788C>T YP_009724390.1:p.Pro1263Leu S S surface glycoprotein S trafficking Circulating variant in the cytoplasmic tail, shown in vitro to increase Spike subunit fusion required for cell entry Barrett 2021.0 https://doi.org/10.1101/2021.01.24.428007 10.1101/2021.01.24.428007 33532777 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22016,22016,22016 W152R,W152R,W152R ,NC_045512.2:g.454T>A,NC_045512.2:g.454T>C YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg ,, S S surface glycoprotein S antibody epitope effects For NTD-binding neutralizing antibody ADI-56479 this mutation causes a 1000x drop in neutralization efficiency. Haslwanter 2021.0 https://doi.org/10.1101/2021.06.10.447999 10.1101/2021.06.10.447999 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S convalescent plasma escape Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S convalescent plasma escape Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S convalescent plasma escape Significant decrease in neutralization across 11 of 16 sera tested 7-17 days post symptoms onset. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr , S S surface glycoprotein S convalescent plasma escape Significant decrease in neutralization across 4 of 16 sera tested 7-17 days post symptoms onset. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp S S surface glycoprotein S convalescent plasma escape No effective neutralization in 1 out of the 4 sera tested. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Multiple individuals in two related households were infected with a newly acquired E484K mutation within the B.1.311 lineage. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient's quarantine period. Sabin 2021.0 https://doi.org/10.1101/2021.10.02.21264415 10.1101/2021.10.02.21264415 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp , S S surface glycoprotein S convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr , S S surface glycoprotein S convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S convalescent plasma escape No effective neutralization in 3 out of the 4 sera tested. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S convalescent plasma escape No effective neutralization in all 4 out of the 4 sera tested. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S convalescent plasma escape No effective neutralization in all 4 out of the 4 sera tested. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S convalescent plasma escape No effective neutralization in 1 out of the 4 sera tested. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23060,23062,23062,23063,23063 Y489H,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,, S S surface glycoprotein S antibody epitope effects Pseudotype for Day 146 virus from a chronically infected patient: resistant to neutralization by mAb C1A-B12, and was still resistant to the affinity enhanced antibodies derived from it (i.e. no affinity maturation effect on neutralization). Clark 2021.0 https://doi.org/10.1016/j.cell.2021.03.027 10.1016/j.cell.2021.03.027 33831372 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S convalescent plasma escape No effective neutralization in 3 out of the 4 sera tested. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S convalescent plasma escape IC50 relative to wildtype drops ~8x in neutralization efficiency between 7-17 days post symptoms onset. Liu 2021.0 https://doi.org/10.1016/j.chom.2021.01.014 10.1016/j.chom.2021.01.014 33535027 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22010 K150E NC_045512.2:g.448A>G YP_009724390.1:p.Lys150Glu S S surface glycoprotein S convalescent plasma escape In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency. Haslwanter 2021.0 https://doi.org/10.1101/2021.06.10.447999 10.1101/2021.06.10.447999 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22016,22016,22016 W152R,W152R,W152R ,NC_045512.2:g.454T>A,NC_045512.2:g.454T>C YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg ,, S S surface glycoprotein S convalescent plasma escape In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency. Haslwanter 2021.0 https://doi.org/10.1101/2021.06.10.447999 10.1101/2021.06.10.447999 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H NC_045512.2:g.284C>T,,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Sera from individuals who have been infected with Delta does not have strong neutralising activity against B.1.621 Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against B.1.621. 2021.0 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24410 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D950N NC_045512.2:g.284C>T,,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Mean 12.4x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. [This is a greater reduction than Beta @ 8.2x] Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21786,21786,21789,22298,22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403,24138 G75V,T76I,T76I,R246_D253delinsN,L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G,T859N NC_045512.2:g.224G>T,NC_045512.2:g.227C>T,NC_045512.2:g.227C>T,NC_045512.2:g.737_757del,NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2576C>A YP_009724390.1:p.Gly75Val,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Arg246_Asp253delinsAsn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr859Asn ,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Mean 3.4x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Mean 2.7x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23062,23062,23063,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Pseudotype for Day 152 virus from a chronically infected patient: although mAb C1A-B12 had no activity against this pseudotype, all three affinity optimized versions were active; the antibody containing the most mutations, C1A-B12.3, was the most potent (IC50 <0.5 μg/mL). Clark 2021.0 https://doi.org/10.1016/j.cell.2021.03.027 10.1016/j.cell.2021.03.027 33831372 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Mean 4.0x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Mean 4.1x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Mean 8.2x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Mean 2.6x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Sera from individuals who have been infected with Delta does not have strong neutralising activity against Beta. Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against Beta. 2021.0 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Relative to B.1, Kappa (B.1.617.1) shows 5.71x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021.0 https://doi.org/10.1101/2021.08.09.21261704 10.1101/2021.08.09.21261704 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22227,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Relative to B.1, Delta (B.1.617.2) shows 3.64x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021.0 https://doi.org/10.1101/2021.08.09.21261704 10.1101/2021.08.09.21261704 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021.0 https://doi.org/10.1101/2021.08.09.21261704 10.1101/2021.08.09.21261704 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910,23011,23012,23039,23039,23040,23373,25045,25046,25046 N450D,N450D,E484K,E484K,Q493R,Q493R,Q493R,T604I,P1162S,P1162S,P1162S NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,,NC_045512.2:g.1450G>A,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1811C>T,,NC_045512.2:g.3484C>T, YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Thr604Ile,YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser ,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.5 post symptom onset. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334,22879,22879,22881,22882,22882,22882,22904,22910,23011,23012 W258R,N440K,N440K,N440K,N440K,N440K,N440K,N450D,N450D,E484K,E484K NC_045512.2:g.772T>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,,NC_045512.2:g.1450G>A YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys ,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.5 post symptom onset. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132 L18F,T20N,P26S,D138Y,R190S NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser ,,,, S S surface glycoprotein S antibody epitope effects "The neutralization titer of NTD-binding mAb159 was 133-fold reduced on P.1 compared to Victoria (~wild type), with only 64% neutralization at 10 μg/mL. Residues 20, 18, and 138 form a cluster underlying the 245–259 loop, which inserts into a groove between the light and heavy chains of Fab 159. In addition, the N-terminal residues preceding residue 18 interact with the antibody and may be perturbed. Given that there is likely a single supersite (""i"") for potent NTD-binding antibodies, the binding of many of these are likely affected. Using 20 potent (primaruly anti-RBD) antibodies, neutralization was measured by a focus reduction neutralization test (FRNT) and compared with neutralization of Victoria (~wild type) and variants B.1.1.7 and B.1.351. Compared to Victoria neutralization by the mAbs was significantly impacted by P.1, with 12/20 showing > 10-fold reduction in FRNT50 titer and a number showing complete knockout of activity. The results with P.1 showed a greater impact compared to B.1.1.7 but were, as expected, similar to those with B.1.351." Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22334,22600,22600,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22986,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,W258R,R346S,R346S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,A475V,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.772T>C,NC_045512.2:g.1038A>C,NC_045512.2:g.1038A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1424C>T,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ala475Val,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments and mutations from variants of concern completely ablates neutralization in 19 of 21 convalescents plasma collected mean 1.5 post symptom onset. [actual Y145del from manuscript substituted with more common Y144del description] Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21604,21604 Q14H,Q14H NC_045512.2:g.42G>T,NC_045512.2:g.42G>C YP_009724390.1:p.Gln14His,YP_009724390.1:p.Gln14His , S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21752,21752 W64R,W64R NC_045512.2:g.190T>C,NC_045512.2:g.190T>A YP_009724390.1:p.Trp64Arg,YP_009724390.1:p.Trp64Arg , S S surface glycoprotein S convalescent plasma escape Mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal iummnuity escape variant. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,23012,23399,23401,23401,23402,23403,23403 E156_R158delinsG,E484Q,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.467_472del,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,, S S surface glycoprotein S syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*13:02. Riou 2021.0 https://doi.org/10.1126/scitranslmed.abj6824 10.1126/scitranslmed.abj6824 34931886 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21624,22022,22216,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24863 R21T,E154K,Q218H,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,H1101D NC_045512.2:g.62G>C,NC_045512.2:g.460G>A,NC_045512.2:g.654G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3301C>G YP_009724390.1:p.Arg21Thr,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Gln218His,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.His1101Asp ,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Abrogates Bamlanivimab neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Significant decrease in combined Etesevimab+Bamlanivimab neutralization except at the highest concentration measured. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021.0 https://doi.org/10.1101/2021.05.04.442663 10.1101/2021.05.04.442663 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22003 K147N NC_045512.2:g.441A>T YP_009724390.1:p.Lys147Asn S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21997,21997,21999,22000,22000,22001 K147E,K147E,K147E,K147E,K147E,K147E NC_045512.2:g.439A>G,,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,,NC_045512.2:g.439A>G YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu ,,,,, S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022 E154K NC_045512.2:g.460G>A YP_009724390.1:p.Glu154Lys S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22323 S254Y NC_045512.2:g.761C>A YP_009724390.1:p.Ser254Tyr S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22304 Y248H NC_045512.2:g.742T>C YP_009724390.1:p.Tyr248His S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334 W258R NC_045512.2:g.772T>C YP_009724390.1:p.Trp258Arg S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Abrogates Bamlanivimab, Etesevimab, or their combined use neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Hoffman 2021.0 https://doi.org/10.1101/2021.05.04.442663 10.1101/2021.05.04.442663 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22340 A260T NC_045512.2:g.778G>A YP_009724390.1:p.Ala260Thr S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893,22893 K444T,K444T ,NC_045512.2:g.1331A>C YP_009724390.1:p.Lys444Thr,YP_009724390.1:p.Lys444Thr , S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp , S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective. Stamatatos 2021.0 https://doi.org/10.1126/science.abg9175 10.1126/science.abg9175 33766944 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23373 T604I NC_045512.2:g.1811C>T YP_009724390.1:p.Thr604Ile S S surface glycoprotein S convalescent plasma escape Mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal iummnuity escape variant. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23429 A623T NC_045512.2:g.1867G>A YP_009724390.1:p.Ala623Thr S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24000 S813I NC_045512.2:g.2438G>T YP_009724390.1:p.Ser813Ile S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective. Stamatatos 2021.0 https://doi.org/10.1126/science.abg9175 10.1126/science.abg9175 33766944 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25045,25046,25046 P1162S,P1162S,P1162S ,NC_045512.2:g.3484C>T, YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser ,, S S surface glycoprotein S convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents mean 1.5 post symptom onset. Schmidt 2021.0 https://doi.org/10.1101/2021.08.06.455491 10.1101/2021.08.06.455491 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23060,23062,23062,23063,23063 Y489H,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,, S S surface glycoprotein S convalescent plasma escape Pseudotype for Day 146 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 146 S pseudotype was resistant to neutralization. Clark 2021.0 https://doi.org/10.1016/j.cell.2021.03.027 10.1016/j.cell.2021.03.027 33831372 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23062,23062,23063,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Pseudotype for Day 152 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 152 S pseudotype was resistant to neutralization. Clark 2021.0 https://doi.org/10.1016/j.cell.2021.03.027 10.1016/j.cell.2021.03.027 33831372 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Pseudotyped viruses for B.1.617 was 2.3-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. [details on the convalescent patient sera collection are not abundantly clear in the preprint] Tada 2021.0 https://doi.org/10.1101/2021.05.14.444076 10.1101/2021.05.14.444076 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23399,23401,23401,23402,23403,23403 E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,, S S surface glycoprotein S convalescent plasma escape Pseudotyped viruses for B.1.618 was 2.5-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. [details on the convalescent patient sera collection are not abundantly clear in the preprint] Tada 2021.0 https://doi.org/10.1101/2021.05.14.444076 10.1101/2021.05.14.444076 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, one third (5/15) of sera neutralized this B.1.351 pseudotype and only three had ID50 titers above 100. Only two of the 15 sera achieved 80% neutralization. Stamatatos 2021.0 https://doi.org/10.1126/science.abg9175 10.1126/science.abg9175 33766944 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, 7 of 15 neutralized this B.1.351 pseudotype that includes the L242del, and only one had titers above 100. Only one of the 15 sera achieved 80% neutralization. [compare to 5 and 1 for pseudotype without the deletion] Stamatatos 2021.0 https://doi.org/10.1126/science.abg9175 10.1126/science.abg9175 33766944 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S convalescent plasma escape VSV pseudotyped with Y453F reduced inhibition by most of the 13 potent convalescent serum/plasma samples tested, albeit with variable efficiency (median increase of serum/plasma titer required for 50% neutralization [NT50] = 1.62x, range = 1.02x to 3.43x), indicating that this RBD mutation may compromise SARS-CoV-2 control by preexisting neutralizing antibody responses. Hoffman 2021.0 https://doi.org/10.1016/j.celrep.2021.109017 10.1016/j.celrep.2021.109017 33857422 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In 34 plasma collected 11-45 days post symptom onset, before B.1.1.7's emergence, neutralization of P.1 decreased 3.1x (comparable to B.1.1.7 at 2.9x). When using plasma from individuals infected with B.1.1.7, only modest (1.8-fold, p=0.0039) reductions in neutralization comparing P.1 with Victoria (~wild type) were observed. Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In 34 plasma collected 11-45 days post symptom onset, before B.1.1.7's emergence, neutralization of P.1 decreased 3.1x (comparable to B.1.1.7 at 2.9x). When using plasma from individuals infected with B.1.1.7, only modest (1.8-fold, p=0.0039) reductions in neutralization comparing P.1 with Victoria (~wild type) were observed. Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 256 for B.1.1.7 virus. Compare to somewhat stronger neutralization titer for wild type (456.1) in the same sera. Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In 34 plasma collected 11-45 days post symptom onset, before B.1.1.7's emergence, neutralization of B.1.351 decreased 13.3x (much more than B.1.1.7 at 2.9x and P.1 at 3.1x). When using plasma from individuals infected with B.1.1.7, reductions in neutralization were significant but less extreme (4.4x) compared with with Victoria (~wild type). Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In 34 plasma collected 11-45 days post symptom onset, before B.1.1.7's emergence, neutralization of B.1.351 decreased 13.3x (much more than B.1.1.7 at 2.9x and P.1 at 3.1x). When using plasma from individuals infected with B.1.1.7, reductions in neutralization were significant but less extreme (4.4x) compared with with Victoria (~wild type). Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Passive immunization with plasma from an early pandemic SARS-CoV-2 patients given to K18-hACE2 transgenic mice did not protect against viral propagation or lethal disease (whereas B.1.1.7 had partial protection and wild type complete protection). B.1.351 triggering significantly altered cytokine profiles than other strains in these mice. Horspool 2021.0 https://doi.org/10.1101/2021.05.05.442784 10.1101/2021.05.05.442784 33972945 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In 34 plasma collected 11-45 days post symptom onset, before B.1.1.7's emergence, neutralization of B.1.351 decreased 13.3x (much more than B.1.1.7 at 2.9x and P.1 at 3.1x). When using plasma from individuals infected with B.1.1.7, reductions in neutralization were significant but less extreme (4.4x) compared with with Victoria (~wild type). Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Passive immunization with plasma from an early pandemic SARS-CoV-2 patients given to K18-hACE2 transgenic mice did not protect against viral propagation or lethal disease (whereas B.1.1.7 had partial protection and wild type complete protection). B.1.351 triggering significantly altered cytokine profiles than other strains in these mice. Horspool 2021.0 https://doi.org/10.1101/2021.05.05.442784 10.1101/2021.05.05.442784 33972945 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Using early pandemic sera (April-June 2020), we observed modestly decreased cross-neutralization of B.1.1.7 pseudotype lentilvirus but a substantial 4.8-fold reduction in cross-neutralization of B.1.351. 2 sera showed zero neutralization of B.1.351. Vidal 2021.0 https://doi.org/10.1128/JVI.00404-21 10.1128/JVI.00404-21 33893169 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In 34 plasma collected 11-45 days post symptom onset, before B.1.1.7's emergence, neutralization of B.1.351 decreased 13.3x (much more than B.1.1.7 at 2.9x and P.1 at 3.1x). When using plasma from individuals infected with B.1.1.7, reductions in neutralization were significant but less extreme (4.4x) compared with with Victoria (~wild type). Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S antibody epitope effects >20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against IgG1 monoclonal antibody ab1. Sun 2021.0 https://doi.org/10.1101/2021.03.22.436481 10.1101/2021.03.22.436481 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Passive immunization with plasma from an early pandemic SARS-CoV-2 patients given to K18-hACE2 transgenic mice did not protect against viral propagation or lethal disease (whereas B.1.1.7 had partial protection and wild type complete protection). B.1.351 triggering significantly altered cytokine profiles than other strains in these mice. Horspool 2021.0 https://doi.org/10.1101/2021.05.05.442784 10.1101/2021.05.05.442784 33972945 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Using early pandemic sera (April-June 2020), we observed modestly decreased cross-neutralization of B.1.1.7 pseudotype lentilvirus but a substantial 4.8-fold reduction in cross-neutralization of B.1.351. 2 sera showed zero neutralization of B.1.351. Vidal 2021.0 https://doi.org/10.1128/JVI.00404-21 10.1128/JVI.00404-21 33893169 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 8 for B.1.351 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera. Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S convalescent plasma escape 0.7x reduction in neutralization by key variant in several variants of concern in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,22811,22812,22813,22813,22813,23011,23012 N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K,E484K NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys ,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape ~7x reduction in neutralization by key B.1.351 lineage RBD variant combination in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Two of the cohort showed no neutralization against this variant. Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. Planas 2021.0 https://doi.org/10.1038/s41591-021-01318-5 10.1038/s41591-021-01318-5 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms had mean ~6x reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Planas 2021.0 https://doi.org/10.1038/s41591-021-01318-5 10.1038/s41591-021-01318-5 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21624,22022,22216,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24863 R21T,E154K,Q218H,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,H1101D NC_045512.2:g.62G>C,NC_045512.2:g.460G>A,NC_045512.2:g.654G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3301C>G YP_009724390.1:p.Arg21Thr,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Gln218His,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.His1101Asp ,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Approximately 2-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021.0 https://doi.org/10.1101/2021.05.04.442663 10.1101/2021.05.04.442663 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Approximately 6-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Hoffman 2021.0 https://doi.org/10.1101/2021.05.04.442663 10.1101/2021.05.04.442663 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,23060,23062,23062,23063,23063,22811,22812,22813,22813,22813,23011,23012,23399,23401,23401,23402,23403,23403 L18F,D80A,D215G,N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape The most significant loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against authentic B.1.351 lineage virus (9.2-fold). Neutralization against 10 convalescent plasma was poorer (18.7x). Tang 2021.0 https://doi.org/10.1101/2021.03.19.436183 10.1101/2021.03.19.436183 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn , S S surface glycoprotein S antibody epitope effects ~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6. Sun 2021.0 https://doi.org/10.1101/2021.03.22.436481 10.1101/2021.03.22.436481 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against P.1 (3.5-fold). Neutralization against 10 convalescent plasma was slightly poorer (3.9-fold). Tang 2021.0 https://doi.org/10.1101/2021.03.19.436183 10.1101/2021.03.19.436183 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against P.1 (3.5-fold). Neutralization against 10 convalescent plasma was slightly poorer (3.9-fold). Tang 2021.0 https://doi.org/10.1101/2021.03.19.436183 10.1101/2021.03.19.436183 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera. Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against P.1 (3.5-fold). Neutralization against 10 convalescent plasma was slightly poorer (3.9-fold). Tang 2021.0 https://doi.org/10.1101/2021.03.19.436183 10.1101/2021.03.19.436183 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera. Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Neutralizing antibodies that were generated following a mild infection with SARS-CoV-2 B.1.128 were effective in vitro, and likely protective, against the SARS-CoV-2 P.1. variant in the majority of individuals based on 60 convalescent sera tested. Mendes-Correa 2021.0 https://doi.org/10.1101/2021.05.11.21256908 10.1101/2021.05.11.21256908 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,, S S surface glycoprotein S convalescent plasma escape Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.249 (1.7-fold). Neutralization against 10 convalescent plasma was somewhat poorer (3.1-fold). Tang 2021.0 https://doi.org/10.1101/2021.03.19.436183 10.1101/2021.03.19.436183 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S convalescent plasma escape As measured by surface plasmon resonance, RBD with the E484K mutation alone showed a mean 19.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma. Tang 2021.0 https://doi.org/10.1101/2021.03.19.436183 10.1101/2021.03.19.436183 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S convalescent plasma escape As measured by surface plasmon resonance, RBD with the N501Y mutation alone showed a mean 2.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma. Tang 2021.0 https://doi.org/10.1101/2021.03.19.436183 10.1101/2021.03.19.436183 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S convalescent plasma escape The only mutation in the B.1.351 lineage that appears to contribute to neutralization reduction (~1.7x across 10 convalescent sera from April 2020 infectees) Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S antibody epitope effects ~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6. Sun 2021.0 https://doi.org/10.1101/2021.03.22.436481 10.1101/2021.03.22.436481 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S convalescent plasma escape Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23604,23604 N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.2042C>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,, S S surface glycoprotein S convalescent plasma escape These key B.1.1.7 mutations as a combination neutralized slightly less well than D614G and this was noticeable in the lack of sera with high neutralizing titer for the viruses across 10 convalescent sera from April 2020 infectees. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His ,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape "Lentiviral pseudotyped with the key mutations from COH.20G/677H (""Ohio"") lineage was neutralized similarly to D614G in 10 convalescent sera from April 2020 infectees." Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920,25249,25249,25249 Y453F,M1229I,M1229I,M1229I NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile ,,, S S surface glycoprotein S convalescent plasma escape Lentiviral pseudotyped with the key mutations from Mink Cluster 5 was neutralized more easily than D614G in 10 convalescent sera from April 2020 infectees. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23401,23402,23403,23403 S477N,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S convalescent plasma escape Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was neutralized slightly less than D614G in 10 convalescent sera from April 2020 infectees. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for 6 convalescent sera." Zhou 2021.0 https://doi.org/10.1101/2021.03.24.436620 10.1101/2021.03.24.436620 33791698 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.8x reduction in IC50 serum dilution concentration for 6 convalescent sera." Zhou 2021.0 https://doi.org/10.1101/2021.03.24.436620 10.1101/2021.03.24.436620 33791698 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,, S S surface glycoprotein S convalescent plasma escape In 9 plasma collected 15 to 28 days after early 2020 infections, neutralization reduced 4.9-fold for B.1.427/B.1.429 compared to wildtype (D614G). In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.427/B.1.429 pseudotyped virus, as well as WT and other VOCs. McCallum 2021.0 https://doi.org/10.1101/2021.03.31.437925 10.1101/2021.03.31.437925 33821281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.351 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the B.1.351 variants used, using the most popular as a stad in] McCallum 2021.0 https://doi.org/10.1101/2021.03.31.437925 10.1101/2021.03.31.437925 33821281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody VH-Fc ab8 Sun 2021.0 https://doi.org/10.1101/2021.03.22.436481 10.1101/2021.03.22.436481 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for P.1 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the P.1 variants used, using the most popular as a stand in] McCallum 2021.0 https://doi.org/10.1101/2021.03.31.437925 10.1101/2021.03.31.437925 33821281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape VSV pseudotype B.1.351 showed 7.86-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections). Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape VSV pseudotype P.1 showed 4.8-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections). Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Loss of neutralizing activity using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.1.7 (1.9-fold). Neutralization against 10 convalescent plasma was poorer. Tang 2021.0 https://doi.org/10.1101/2021.03.19.436183 10.1101/2021.03.19.436183 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Loss of neutralizing activity using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.1.7 (1.9-fold). Neutralization against 10 convalescent plasma was poorer. Tang 2021.0 https://doi.org/10.1101/2021.03.19.436183 10.1101/2021.03.19.436183 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H] Supasa 2021.0 https://doi.org/10.1016/j.cell.2021.02.033 10.1016/j.cell.2021.02.033 33743891 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Loss of neutralizing activity using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.1.7 (1.9-fold). Neutralization against 10 convalescent plasma was poorer. Tang 2021.0 https://doi.org/10.1101/2021.03.19.436183 10.1101/2021.03.19.436183 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H] Supasa 2021.0 https://doi.org/10.1016/j.cell.2021.02.033 10.1016/j.cell.2021.02.033 33743891 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape NTD-specific nAbs showed a substantial (3-450x) decrease in neutralization potency against the recently reported highly transmissible B.1.1.7 variant of concern, whereas RBD-specific nAbs were either unaffected or showed lower decreases in potency. Graham 2021.0 https://doi.org/10.1016/j.immuni.2021.03.023 10.1016/j.immuni.2021.03.023 33836142 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21993,21995 H146del,H146del NC_045512.2:g.436_438del,NC_045512.2:g.436_438del YP_009724390.1:p.His146del,YP_009724390.1:p.His146del , S S surface glycoprotein S convalescent plasma escape Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient. McCarthy 2021.0 https://doi.org/10.1126/science.abf6950 10.1126/science.abf6950 33536258 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln S S surface glycoprotein S antibody epitope effects >20% (ELISA significance threshold) drop in antibody binding by this variant against monoclonal antibody VH-Fc ab8. Sun 2021.0 https://doi.org/10.1101/2021.03.22.436481 10.1101/2021.03.22.436481 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990 Y145del,Y145del NC_045512.2:g.432_434del,NC_045512.2:g.432_434del YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del , S S surface glycoprotein S convalescent plasma escape Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient. McCarthy 2021.0 https://doi.org/10.1126/science.abf6950 10.1126/science.abf6950 33536258 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22294,22302 L244F,Y248del NC_045512.2:g.732A>C,NC_045512.2:g.743_745del YP_009724390.1:p.Leu244Phe,YP_009724390.1:p.Tyr248del , S S surface glycoprotein S convalescent plasma escape Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient. McCarthy 2021.0 https://doi.org/10.1126/science.abf6950 10.1126/science.abf6950 33536258 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape A 1.8-fold drop in FRNT50 for B.1.351 was observed in 44 sera collected between 1 and 301 post-infection. Bates 2021.0 https://doi.org/10.1101/2021.04.04.21254881 10.1101/2021.04.04.21254881 33851185 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In 34 convalescent cases 4–9 weeks following infection in June 2020, before the emergence of B.1.1.7, neutralization titers against B.1.351 were, on average, 13.3-fold reduced compared with an early Victoria sample (p < 0.0001). Significantly, 18 of 34 samples failed to reach 50% neutralization at a plasma dilution of 1:20, with a number showing a near total reduction of neutralization activity. In 13 convalescent cases 4–9 weeks following infection with B.1.1.7, neutralization titers against B.1.351 were, on average, 3.1-fold reduced compared with an early Victoria sample (p < 0.0001). Zhou 2021.0 https://doi.org/10.1016/j.cell.2021.02.037 10.1016/j.cell.2021.02.037 33730597 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Neutralization capacity GMT of 27 subjects' sera post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed. Collier 2021.0 https://doi.org/10.1038/s41586-021-03412-7 10.1038/s41586-021-03412-7 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:02. Riou 2021.0 https://doi.org/10.1126/scitranslmed.abj6824 10.1126/scitranslmed.abj6824 34931886 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Neutralization capacity GMT of 27 subjects' sera post-infection was markedly worse against B.1.1.7 + E484K than the lineage alone, with a 11.4x drop. Collier 2021.0 https://doi.org/10.1038/s41586-021-03412-7 10.1038/s41586-021-03412-7 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In convalescent sera one month or more post-infection in Spring 2020, an average 6.5x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.4x decrease against the full P.1 type vs WA-1 was observed, with better full P.1 ID50 reciprocal value compared to the 10-mutation model. Wang 2021.0 https://doi.org/10.1101/2021.03.01.433466 10.1101/2021.03.01.433466 33688656 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In a Syrian hamster model, B.1.351 variant virus had >4x reduction in YRNT90 (measure of neutralization) using wild type convalescent sera. PG: Note that exact sequence for B.1.351 used was not disclosed. Cochin 2021.0 https://doi.org/10.1101/2021.04.19.440435 10.1101/2021.04.19.440435 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln S S surface glycoprotein S convalescent plasma escape In 3 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, E484Q shows a notably resistant profile, comparable to or even more resistant than E484K at later time points (i.e. more resistant to immune cell somatic mutation evolution), see Figure 5a,b. Subject C 32 days post-infection showed >>10 fold reduction in neutralization, reducing to ~10-fold by day 104. Subject B 26 days post-infection showed ~10 fold reduction in neutralization, reducing to ~4x at day 113. Notably, Subject B also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 32, and no E484K immune escape at day 104. Subject I 26 days post-infection showed ~10 fold reduction in neutralization, with no reduction in escape at day 102. Notably, Subject I also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 26, and no E484K immune escape at day 102. Greaney 2021.0 https://doi.org/10.1016/j.chom.2021.02.003 10.1016/j.chom.2021.02.003 33592168 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro S S surface glycoprotein S convalescent plasma escape S494P frequently engages in interactions with antibodies but not with ACE2. It reduces antibody neutralization of all 16 convalescent sera tested, averaging WT ratio of 0.41+-0.08 (less dramatic than E484K). This amino acid emerges as an additional hotspot for immune evasion and a target for therapies, vaccines and diagnostics. It has emerged independently in multiple lineages. Alenquer 2021.0 https://doi.org/10.1101/2021.04.22.441007 10.1101/2021.04.22.441007 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro S S surface glycoprotein S convalescent plasma escape S494P frequently engages in interactions with antibodies but not with ACE2. It reduces antibody neutralization of all 16 convalescent sera tested, averaging WT ratio of 0.41+-0.08 (less dramatic than E484K). This amino acid emerges as an additional hotspot for immune evasion and a target for therapies, vaccines and diagnostics. It has emerged independently in multiple lineages. Alenquer 2021.0 https://doi.org/10.1101/2021.04.22.441007 10.1101/2021.04.22.441007 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro S S surface glycoprotein S convalescent plasma escape In 2 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, S484P shows a slightly resistent profile across both timepoints (i.e. resistant to immune cell somatic mutation evolution) Greaney 2021.0 https://doi.org/10.1016/j.chom.2021.02.003 10.1016/j.chom.2021.02.003 33592168 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S antibody epitope effects >60% drop in antibody binding (ELISA) by this variant against monoclonal antibody VH-Fc ab8. Sun 2021.0 https://doi.org/10.1101/2021.03.22.436481 10.1101/2021.03.22.436481 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Sera neutralized the B1.1.7 isolate with a lower potency (2-fold; 95% CL: 1.5 – 3-fold), and those with the lowest homotypic neutralizing potency had undetectable heterotypic potency (2/25). Skelly 2021.0 https://doi.org/10.21203/rs.3.rs-226857/v1 10.21203/rs.3.rs-226857/v1 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals (5/9) and recipients of a only a single dose of mRNA vaccine (10/11) – heterotypic neutralization dropped to negligible levels, particularly against B.1.351. Skelly 2021.0 https://doi.org/10.21203/rs.3.rs-226857/v1 10.21203/rs.3.rs-226857/v1 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China). Hu 2021.0 https://doi.org/10.1101/2021.01.22.427749 10.1101/2021.01.22.427749 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China). Hu 2021.0 https://doi.org/10.1101/2021.01.22.427749 10.1101/2021.01.22.427749 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Average ~10-fold reduction in neutralization efficacy in convalescent sera of 16 health workers infected in Spring 2020. Alenquer 2021.0 https://doi.org/10.1101/2021.04.22.441007 10.1101/2021.04.22.441007 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S convalescent plasma escape Average ~5-fold reduction in neutralization efficacy in convalescent sera of 16 health workers infected in Spring 2020. Alenquer 2021.0 https://doi.org/10.1101/2021.04.22.441007 10.1101/2021.04.22.441007 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S convalescent plasma escape Average ~5-fold reduction in neutralization efficacy in convalescent sera of 16 health workers infected in Spring 2020. Alenquer 2021.0 https://doi.org/10.1101/2021.04.22.441007 10.1101/2021.04.22.441007 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S convalescent plasma escape "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.3x reduction in IC50 serum dilution concentration for 6 convalescent sera." Zhou 2021.0 https://doi.org/10.1101/2021.03.24.436620 10.1101/2021.03.24.436620 33791698 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23604,23604 N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.2042C>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,, S S surface glycoprotein S convalescent plasma escape Slight neutralization improvement on average in 16 health workers' convalescent sera. Alenquer 2021.0 https://doi.org/10.1101/2021.04.22.441007 10.1101/2021.04.22.441007 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S convalescent plasma escape Observed ~2x decrease on average in 16 health workers' convalescent sera. Alenquer 2021.0 https://doi.org/10.1101/2021.04.22.441007 10.1101/2021.04.22.441007 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23604,23604 N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.2042C>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,, S S surface glycoprotein S convalescent plasma escape One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency. Alenquer 2021.0 https://doi.org/10.1101/2021.04.22.441007 10.1101/2021.04.22.441007 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,25186 L5F,Q1208H NC_045512.2:g.13C>T,NC_045512.2:g.3624G>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Gln1208His , S S surface glycoprotein S convalescent plasma escape Four the convalescent sera tested showed 4-fold or greater improvement in neutralization efficiency. Alenquer 2021.0 https://doi.org/10.1101/2021.04.22.441007 10.1101/2021.04.22.441007 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,, S S surface glycoprotein S convalescent plasma escape Antibody neutralization assays showed 6.7-fold resistence against 7/8 convalescent plasma. Deng 2021.0 https://doi.org/10.1101/2021.03.07.21252647 10.1101/2021.03.07.21252647 33758899 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape The neutralizing activity of 16/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.351, with similar results for the live virus. Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu S S surface glycoprotein S antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody ab8 Sun 2021.0 https://doi.org/10.1101/2021.03.22.436481 10.1101/2021.03.22.436481 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape The neutralizing activity of 8/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.1.7, yet almost no effect was detected using the live B.1.1.7 virus. Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape The neutralizing activity of 8/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.1.7, yet almost no effect was detected using the live B.1.1.7 virus. Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Neutralization activity of convalescent sera tested decreased <2x with this B.1.1.7 pseudotyped virus. Shen 2021.0 https://doi.org/10.1101/2021.01.27.428516 10.1101/2021.01.27.428516 33532764 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape The neutralizing activity of 8/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.1.7, yet almost no effect was detected using the live B.1.1.7 virus. Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Neutralization activity of convalescent sera tested decreased <2x with this B.1.1.7 pseudotyped virus. Shen 2021.0 https://doi.org/10.1101/2021.01.27.428516 10.1101/2021.01.27.428516 33532764 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Maximum fold-decrease in potency for the serum samples from mild illness was 8.2 but the majority of samples showed less than a 3-fold change. Similarly, the maximum decrease seen for samples from hospitalized patients was a 9.1-fold change, but most of the samples showed minimal change in the potency of their neutralization. Overall, three samples from each cohort (8%) showed a 5–10-fold reduction, but as they were potently neutralizing sera, the reduced ID50 values were still >1:100. Rees-Spear 2021.0 https://doi.org/10.1101/2021.01.15.426849 10.1101/2021.01.15.426849 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape The neutralizing activity of 8/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.1.7, yet almost no effect was detected using the live B.1.1.7 virus. Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Neutralization activity of convalescent sera tested decreased <2x with this B.1.1.7 pseudotyped virus. Shen 2021.0 https://doi.org/10.1101/2021.01.27.428516 10.1101/2021.01.27.428516 33532764 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Maximum fold-decrease in potency for the serum samples from mild illness was 8.2 but the majority of samples showed less than a 3-fold change. Similarly, the maximum decrease seen for samples from hospitalized patients was a 9.1-fold change, but most of the samples showed minimal change in the potency of their neutralization. Overall, three samples from each cohort (8%) showed a 5–10-fold reduction, but as they were potently neutralizing sera, the reduced ID50 values were still >1:100. Rees-Spear 2021.0 https://doi.org/10.1101/2021.01.15.426849 10.1101/2021.01.15.426849 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Neutralizing antibody titers of 2/20 (10%) samples showed >10x reduction (sera collected ~1mo post Jan 2020 first wave in China). Neutralizing antibody titers of 8/20 samples (40%) decreased below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China). Hu 2021.0 https://doi.org/10.1101/2021.01.22.427749 10.1101/2021.01.22.427749 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody ab8 Sun 2021.0 https://doi.org/10.1101/2021.03.22.436481 10.1101/2021.03.22.436481 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S convalescent plasma escape Neutralization activity of convalescent sera tested decreased ~2x with this B.1.1.7 pseudotyped virus. Shen 2021.0 https://doi.org/10.1101/2021.01.27.428516 10.1101/2021.01.27.428516 33532764 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S convalescent plasma escape Neutralization activity of convalescent sera tested decreased ~2x with this B.1.1.7 pseudotyped virus. Shen 2021.0 https://doi.org/10.1101/2021.01.27.428516 10.1101/2021.01.27.428516 33532764 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S convalescent plasma escape In 30 samples collected 111 to 260 days post onset of symptoms, the covalescent plasma can neutralize both the reference USA-WA1/2020 strain and the mouse adapted strain that contains the N501Y spike mutation with similar efficiency. Rathnasinghe 2021.0 https://doi.org/10.1101/2021.01.19.21249592 10.1101/2021.01.19.21249592 33501468 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala S S surface glycoprotein S convalescent plasma escape The neutralizing activity of 6/20 convalescent sera was significantly lower against this single variant pseudotyped virus model, showing similar patterns to the pseudotyped virus model of B.1.1.7. Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape B.1.1.351 in 19 convalescent human sera ~1mo post infection had mild to moderate resistence against all samples Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Demonstrate (via competitive assays in human and mouse) immune escape from polyclonal antibodies induced by vaccination or infection, comparable to what was previously shown with monoclonal antibodies for N501Y and more importantly for E484K. Even though viral mutations may more strongly affect monoclonal antibodies than sera activity, the latter may also be reduced as confirmed here. Vogel 2021.0 https://doi.org/10.1101/2021.03.04.433887 10.1101/2021.03.04.433887 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape Demonstrate (via competitive assays in human and mouse) immune escape from polyclonal antibodies induced by vaccination or infection, comparable to what was previously shown with monoclonal antibodies for N501Y and more importantly for E484K. Even though viral mutations may more strongly affect monoclonal antibodies than sera activity, the latter may also be reduced as confirmed here. Vogel 2021.0 https://doi.org/10.1101/2021.03.04.433887 10.1101/2021.03.04.433887 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape In 19 convalescent human sera ~1mo post infection had mild to moderate resistence against most samples Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibodies ab8 and IgG1 ab1. Complete loss for the same antibodies was also observed against S1 pseudotyped and full Spike protein trimers with both B.1.351 and P.1 lineage variants, with slight binding signal for P.1 against IgG1 at the highest concentration tested (1uM). Complete loss of neutralization by these two antibodies was also observed. Sun 2021.0 https://doi.org/10.1101/2021.03.22.436481 10.1101/2021.03.22.436481 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S convalescent plasma escape In 19 convalescent human sera ~1mo post infection had mild to moderate resistence against all samples. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape B.1.1.248 variant constellation in 10 convalescent human sera ~1mo post infection had mild to moderate resistence against most samples, P=0.0020. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S convalescent plasma escape In 19 convalescent human sera ~1mo post infection, Two-tailed Wilcoxon matched-pairs signed-rank test shows mild resistence P=0.0361. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape B.1.1.7 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0039 for mild resistence. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape B.1.1.351 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0020 for moderate resistence. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S convalescent plasma escape Remarkably, several of the E484 escape mutants were resistant to neutralization at the highest concentration (1:80 initial dilution) of all 4 convalescent sera tested (triplicate experiments). Against a wider panel of 16 convalescent plasma (no replicates), all but one show major resistance. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S convalescent plasma escape Remarkably, several of the E484 escape mutants were resistant to neutralization at the highest concentration (1:80 initial dilution) of all 4 convalescent sera tested (triplicate experiments). Against a wider panel of 16 convalescent plasma (no replicates), all but one show major resistance. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S convalescent plasma escape The neutralizing activity of 15/20 convalescent sera was significantly lower against this pseudotyped virus model Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S convalescent plasma escape Remarkably, several of the E484 escape mutants were resistant to neutralization at the highest concentration (1:80 initial dilution) of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), all but one show major resistance. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S antibody epitope effects 10 of 14 RBD-specific mAbs that showed at least 10-fold reduced neutralization of B.1.427/B.1.429 variant pseudotype (S13I, W152C, and L452R) were also found to poorly bind to just a L452R RBD mutant, demonstrating a role for this mutation as an escape mechanism for certain RBD-targeting mAbs. McCallum 2021.0 https://doi.org/10.1101/2021.03.31.437925 10.1101/2021.03.31.437925 33821281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn , S S surface glycoprotein S convalescent plasma escape Improvement in neutralization capability of all 4 convalescent sera tested. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp S S surface glycoprotein S convalescent plasma escape Decrease in neutralization capability of all 4 convalescent sera tested (1 ablated). Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,, S S surface glycoprotein S antibody epitope effects 14 of 34 RBD-specific mAbs showed reduced neutralization to the B.1.427/B.1.429 variant pseudotype. McCallum 2021.0 https://doi.org/10.1101/2021.03.31.437925 10.1101/2021.03.31.437925 33821281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp , S S surface glycoprotein S convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations). Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys S S surface glycoprotein S convalescent plasma escape Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr , S S surface glycoprotein S convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations), triple replicates. Against a broader panel of 16 convalescent plasma (no replicates), reductions in neutralization are considerably less dramatic in pattern, and sometime neutralization increases. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S convalescent plasma escape Ablation of neutralization capability of 3 of 4 convalescent sera tested, the other is significantly hindered. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S convalescent plasma escape Mixed bag of mild positive and negative changes in neutralization capability of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), 10 show low neutralization. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600 S13I NC_045512.2:g.38G>T YP_009724390.1:p.Ser13Ile S S surface glycoprotein S antibody epitope effects The S13I mutation dampened binding of 5 mAbs and abrogated binding of 5 additional mAbs out of 11 neutralizing mAbs evaluated. Predicted to shift the signal peptide cleavage site from S13-Q14 to C15-V16, which can affect NTD conformation. PG: in saying S12F does not shift the signal peptide nor affect mAb binding, this manuscript appears to contradict the text of McCallum et al.'s earlier 2021 manuscript stating that S12F *does* affected some mAb binding via putative signal peptide shift. McCallum 2021.0 https://doi.org/10.1101/2021.03.31.437925 10.1101/2021.03.31.437925 33821281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S convalescent plasma escape Modest decrease in in neutralization capability of all 4 convalescent sera tested. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (3 ablations). Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro S S surface glycoprotein S convalescent plasma escape Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23103 S477N,S514F NC_045512.2:g.1430G>A,NC_045512.2:g.1541C>T YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Ser514Phe , S S surface glycoprotein S convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations). Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape "Nearly half (21 of 44, 48%) of early pandemic exposure convalescent plasma/sera failed to neutralize the 501Y.V2 (""South African"") lineage pseudovirus construct Only 3 of 44 convascent sera (those with the highest titer, which correlated direectly with initial infection severity) had high neutralization against this 501Y.V2 PG: note that lineage variant R246I was excluded from the text in reference to these sera assays, not sure if that was an oversight." Wibmer 2021.0 https://doi.org/10.1101/2021.01.18.427166 10.1101/2021.01.18.427166 33501446 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape "Nearly half (21 of 44, 48%) of early pandemic exposure convalescent plasma/sera failed to neutralize the 501Y.V2 (""South African"") lineage pseudovirus construct Only 3 of 44 convascent sera (those with the highest titer, which correlated direectly with initial infection severity) had high neutralization against this 501Y.V2 PG: note that lineage variant R246I was excluded from the text in reference to these sera assays, not sure if that was an oversight." Wibmer 2021.0 https://doi.org/10.1101/2021.01.18.427166 10.1101/2021.01.18.427166 33501446 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape The 501Y.V2 to first wave IC50 ratio ranged from 6 to 200-fold. Averaging across all 7 participant convalescent sera highlighted the dramatic decrease in sensitivity to neutralization of authentic 501Y.V2 variants. PG: I'm purposefully ignoring D614G and A701V as contributors Cele 2021.0 https://doi.org/10.1038/s41586-021-03471-w 10.1038/s41586-021-03471-w 33780970 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S convalescent plasma escape "27% of 44 early pandemic exposure convalescent plasma/sera lose all activity against a RBD triple mutant pseudovirus (RBD mutatants of the 501Y.V2 ""South African"" lineage), while only 23% retained high titres" Wibmer 2021.0 https://doi.org/10.1101/2021.01.18.427166 10.1101/2021.01.18.427166 33501446 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22018 W152C NC_045512.2:g.456G>T YP_009724390.1:p.Trp152Cys S S surface glycoprotein S antibody epitope effects The W152C mutation reduced recognition of six NTD neutralizing mAbs, including a complete loss of binding for two of them, with a complementary pattern to that observed for S13I (also found in lineage B.1.427/B.1.429) out of 11 neutralizing mAbs evaluated. McCallum 2021.0 https://doi.org/10.1101/2021.03.31.437925 10.1101/2021.03.31.437925 33821281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22005 N148S NC_045512.2:g.443A>G YP_009724390.1:p.Asn148Ser S S surface glycoprotein S convalescent plasma escape Strong positive selection (up to 72% of supernatant sequences) under six rounds of COV47 convalescent plasma passage Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22011 K150R NC_045512.2:g.449A>G YP_009724390.1:p.Lys150Arg S S surface glycoprotein S convalescent plasma escape Positive selection (up to 18% of supernatant sequences) under two rounds of COV47 convalescent plasma passage Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22010 K150E NC_045512.2:g.448A>G YP_009724390.1:p.Lys150Glu S S surface glycoprotein S convalescent plasma escape Strong positive selection (up to 40% of supernatant sequences) under three rounds of COV47 convalescent plasma passage Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444R NC_045512.2:g.1331A>G YP_009724390.1:p.Lys444Arg S S surface glycoprotein S convalescent plasma escape Positive selection (up to 20% of supernatant sequences) under two rounds of COV-NY convalescent plasma passage, eliminated in rounds three and four Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn , S S surface glycoprotein S convalescent plasma escape Positive selection (up to 14% of supernatant sequences) after COV-NY convalescent plasma assay Weisblum 2020.0 https://doi.org/10.1101/2020.07.21.214759 10.1101/2020.07.21.214759 32743579 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:01. Riou 2021.0 https://doi.org/10.1126/scitranslmed.abj6824 10.1126/scitranslmed.abj6824 34931886 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018 S13I,W152C NC_045512.2:g.38G>T,NC_045512.2:g.456G>T YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys , S S surface glycoprotein S antibody epitope effects The B.1.427/B.1.429 S13I/W152C NTD did not bind to any NTD-directed neutralizing mAbs, which are known to target a single antigenic site (antigenic site i), whereas binding of the non-neutralizing S2L20 mAb to the NTD antigenic site iv was not affected by any mutants, confirming proper retention of folding. McCallum 2021.0 https://doi.org/10.1101/2021.03.31.437925 10.1101/2021.03.31.437925 33821281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23948 D796H NC_045512.2:g.2386G>C YP_009724390.1:p.Asp796His S S surface glycoprotein S convalescent plasma escape Fatal COVID-19 complications in immunocomprimised patient after immune escape from convalescent plasma Kemp 2020.0 https://doi.org/10.1101/2020.12.05.20241927 10.1101/2020.12.05.20241927 33398302 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S convalescent plasma escape This mutation occurred in 100% of sequenced virions after 12 passages and led to a 4-fold decrease in convalescent plasma neutralization activity Andreano 2020.0 https://doi.org/10.1101/2020.12.28.424451 10.1101/2020.12.28.424451 33398278 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990 Y145del,Y145del NC_045512.2:g.432_434del,NC_045512.2:g.432_434del YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del , S S surface glycoprotein S convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22936 K458N NC_045512.2:g.1374G>T YP_009724390.1:p.Lys458Asn S S surface glycoprotein S convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22976 I472V NC_045512.2:g.1414A>G YP_009724390.1:p.Ile472Val S S surface glycoprotein S convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val S S surface glycoprotein S convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Contrary to other reports on N501Y containing lineages (i.e. with additional mutations), N501Y alone may have an even greater affinity for a human monoclonal antibody specific for wild type. These results suggest that the individual N501Y mutation does not contribute to altered viral properties by itself, but may contribute to a collective conformational shift produced by multiple mutations. Klegerman 2021.0 https://doi.org/10.1101/2021.04.26.441517 10.1101/2021.04.26.441517 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu S S surface glycoprotein S convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Resistent to 3 individual sera at >4x Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2:g.2492C>T YP_009724390.1:p.Ala831Val S S surface glycoprotein S convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Testing against B.1.351 the 20 most effective mAbs (19 anti-RBD, 1 anti-NTD) from a screen of 377 against wild type, 4 of 20 antibodies had >10-fold fall in neutralization titers, with most of these showing a complete knockout of activity. This is in line with the key roles of K417, E484, and N501, in particular E484, in antibody recognition of the ACE2 interaction surface of the RBD. Regeneron mAb cocktail: The neutralization of REGN10987 was unaffected by B.1.351, while REGN10933 was severely impaired (773-fold). AstraZeneca mAb cocktail: Neutralization by the AZ pair of antibodies was little affected on B.1.351 compared with Victoria. Zhou 2021.0 https://doi.org/10.1016/j.cell.2021.02.037 10.1016/j.cell.2021.02.037 33730597 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Of 50 mAbs tested, major loss of neutralization observed for S2X128, S2D8, S2X192, S2D19, S2H14, S2H19. Collier 2021.0 https://doi.org/10.1038/s41586-021-03412-7 10.1038/s41586-021-03412-7 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Of 50 mAbs tested, major loss of neutralization observed for S2N28, S2X615, S2N12, S2X192, S2H7, S2X16, S2X58, S2H70, S2X613, S2D19, S2N22, S2D32, S2H58, S2M11, S2D106, S2X30. Collier 2021.0 https://doi.org/10.1038/s41586-021-03412-7 10.1038/s41586-021-03412-7 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Amongst RBD-targeting Emergency Use Authorized monoclonal antibody treatments CB6, LY-CoV555 and REGN10933 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1, but REGN10987 activity remains strong. RBD-targeting monoclonal antibodies 2-15 and C121 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. N terminal domain targeting monoclonal antibodies 5-7, 4-8, 4-18 and 2-17 have abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. Wang 2021.0 https://doi.org/10.1101/2021.03.01.433466 10.1101/2021.03.01.433466 33688656 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Monoclonal antibodies 13G9 and 58G6 maintain fairly high neutralization potency, compared to others interfacing with E484K. Li 2021.0 https://doi.org/10.1101/2021.04.19.440481 10.1101/2021.04.19.440481 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects ~20x resistence to mAb CQ038 by B.1.1.7 pseudotyped virus Hu 2021.0 https://doi.org/10.1101/2021.01.22.427749 10.1101/2021.01.22.427749 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Abolished neutralization by mAbs CQ026 and CQ038, greatly diminished neutralization by CQ012 and CQ046. Hu 2021.0 https://doi.org/10.1101/2021.01.22.427749 10.1101/2021.01.22.427749 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22377,22377 P272L,P272L NC_045512.2:g.815C>T, YP_009724390.1:p.Pro272Leu,YP_009724390.1:p.Pro272Leu , S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*08:01. Dolton 2021.0 https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf 10.1101/2021.06.21.21259010v2.full.pdf not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22971,22974 T470N,E471V NC_045512.2:g.1409C>A,NC_045512.2:g.1412A>T YP_009724390.1:p.Thr470Asn,YP_009724390.1:p.Glu471Val , S S surface glycoprotein S antibody epitope effects This mutation prevents neutralization by COVA2-29 (cluster I), COVA2-07 (cluster III) and COVA2-02 (cluster VII). It also reduces the activity of the most potent mAb COVA1-18 (cluster I) by 3-fold, whereas this mAb is only minimally affected by other mutations. Moreover, TEI470-2NVP lowers the potency of the structurally unmapped non-RBD cluster XI mAb, COVA1-21, to the limit of detection. Thus, this mutation negatively impacts the most mAbs, including representatives from four separate epitope clusters. Rees-Spear 2021.0 https://doi.org/10.1101/2021.01.15.426849 10.1101/2021.01.15.426849 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22926,22927,22927,22928,22930,22930 F456L,F456L,F456L,F456L,F456L,F456L NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>A,NC_045512.2:g.1366T>C,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>A,NC_045512.2:g.1368T>G YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu ,,,,, S S surface glycoprotein S antibody epitope effects This double substitution reduces neutralization by RBD-specific mAbs from different clusters, specifically, the cluster I mAb COVA2-29, cluster III mAb COVA2-07 and cluster VI mAb COVA1-12. For COVA1-12 all neutralization activity is abolished, while COVA2-07 activity is just below the level required to calculate an IC50 value. Rees-Spear 2021.0 https://doi.org/10.1101/2021.01.15.426849 10.1101/2021.01.15.426849 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893,22893 K444T,K444T ,NC_045512.2:g.1331A>C YP_009724390.1:p.Lys444Thr,YP_009724390.1:p.Lys444Thr , S S surface glycoprotein S antibody epitope effects Results in 3.7-fold drop in neutralization potency for COVA2-29, which is a cluster I RBD141 specific antibody. Rees-Spear 2021.0 https://doi.org/10.1101/2021.01.15.426849 10.1101/2021.01.15.426849 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model. Shen 2021.0 https://doi.org/10.1101/2021.01.27.428516 10.1101/2021.01.27.428516 33532764 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model. Shen 2021.0 https://doi.org/10.1101/2021.01.27.428516 10.1101/2021.01.27.428516 33532764 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects "Lessens the potency of mAbs COVA2-17 (~5x, similar to N501Y alone), COVA1-12 (~11x) and COVA1-21 (>100x), which do not compete allosterically." Rees-Spear 2021.0 https://doi.org/10.1101/2021.01.15.426849 10.1101/2021.01.15.426849 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects B.1.351 pseudotyped virus model ablates neutralization by RBD-directed mAbs CB6, 4-20, 2-4, 2-43, 910-30, 2-302-15, LY-Cov555, C121. B.1.351 pseudotyped virus model severely impairs neutralization by RBD-directed mAb 1-20. B.1.351 pseudotyped virus model impairs neutralization by RBD-directed mAb REGN10933. B.1.351 pseudotyped virus model ablates neutralization by N-terminal-domain-directed mAbs 5-24, 4-8, 4A8, 4-19. B.1.351 pseudotyped virus model severely impairs neutralization by N-terminal-domain-directed mAb 2-17. B.1.351 pseudotyped virus model impairs neutralization by N-terminal-domain-directed mAb 5-7. PG: Live virus data for the same mAbs is similar, but 1-20 becomes severally impaired, REGN10933 activity is ablated, and Brii-196 becomes impaired. Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22377,22377 P272L,P272L NC_045512.2:g.815C>T, YP_009724390.1:p.Pro272Leu,YP_009724390.1:p.Pro272Leu , S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*02:01. Dolton 2021.0 https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf 10.1101/2021.06.21.21259010v2.full.pdf not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects B.1.1.7 pseudotyped virus model impairs binding by RBD-directed mAb 910-30. B.1.1.7 pseudotyped virus model abolishes N-terminal-domain-directed mAbs 5-24, 4-8, and 4A8. B.1.1.7 pseudotyped virus model impairs binding by N-terminal-domain-directed mAbs 2-17, 4-19, 5-7. Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala S S surface glycoprotein S antibody epitope effects Abolishes neutralizing activity of N-terminal-domain-directed mAb 4-19. Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S antibody epitope effects 10-fold reduction in binding efficiency vs wild type for MAb REGN10933. Rappazzo 2021.0 https://doi.org/10.1126/science.abf4830 10.1126/science.abf4830 33495307 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>C,NC_045512.2:g.1038A>T YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser , S S surface glycoprotein S antibody epitope effects Resistent to class 2/3 antibody C603. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>C,NC_045512.2:g.1038A>T YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser , S S surface glycoprotein S antibody epitope effects Resistent to class 2/3 antibody C603. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>C,NC_045512.2:g.1038A>T YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser , S S surface glycoprotein S antibody epitope effects Clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Riou 2021.0 https://doi.org/10.1126/scitranslmed.abj6824 10.1126/scitranslmed.abj6824 34931886 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn , S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn , S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn , S S surface glycoprotein S antibody epitope effects Abolishes binding efficiency vs wild type for mAb REGN10933. Rappazzo 2021.0 https://doi.org/10.1126/science.abf4830 10.1126/science.abf4830 33495307 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Reynolds 2021.0 https://doi.org/10.1126/science.abh1282 10.1126/science.abh1282 33931567 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr , S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp , S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows some resistence across all antibodies tested. Liu 2021.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02. Motozono 2021.0 https://doi.org/10.1016/j.chom.2021.06.006 10.1016/j.chom.2021.06.006 34171266 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" Wibmer 2021.0 https://doi.org/10.1101/2021.01.18.427166 10.1101/2021.01.18.427166 33501446 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" Wibmer 2021.0 https://doi.org/10.1101/2021.01.18.427166 10.1101/2021.01.18.427166 33501446 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects B.1.1.248 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07. B.1.1.248 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2676. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990,23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604 Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects B.1.1.7 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2489. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S antibody epitope effects B.1.1.351 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. B.1.1.351 variant constellation ablates Class 3 N-terminal domain targeting antibodies COV2-2489 and COV2-2676 (the only two tested). Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S antibody epitope effects 5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs) Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S antibody epitope effects 5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs) Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn ,,,, S S surface glycoprotein S antibody epitope effects Pseudotyped virus model ablates binding by RBD-directed mAbs CB6 and 910-30 (targeting the inner side of the RBD). Pseudotyped virus model impairs binding by RBD-directed mAbs 4-20 and REGN10933. Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val S S surface glycoprotein S T cell evasion This mutation causes a greater than 100x fold change in IC50 of Ensovibep. Rothenberger 2021.0 https://doi.org/10.1101/2021.02.03.429164v4 10.1101/2021.02.03.429164v4 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2:g.1456T>C YP_009724390.1:p.Phe486Leu S S surface glycoprotein S T cell evasion This mutation causes a greater than 100x fold change in IC50 of Ensovibep. Rothenberger 2021.0 https://doi.org/10.1101/2021.02.03.429164v4 10.1101/2021.02.03.429164v4 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus) Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus) Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 E156_R158delinsG,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.467_472del,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,, S S surface glycoprotein S syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2.5x. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S antibody epitope effects Massive reduction in binding efficiency vs wild type for mAb LY-CoV555. Rappazzo 2021.0 https://doi.org/10.1126/science.abf4830 10.1126/science.abf4830 33495307 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C, YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser ,, S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 5 antibodies. Liu 2020.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser ,,,,, S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-32. Liu 2020.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01. Liu 2020.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro S S surface glycoprotein S antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01. Liu 2020.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala S S surface glycoprotein S T cell evasion One individual of 30 in the study, with HLA supertype HLA*A24:02, had a linear epitope that overlaps this variant of concern. Redd 2021.0 https://doi.org/10.1101/2021.02.11.21251585 10.1101/2021.02.11.21251585 33594378 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro S S surface glycoprotein S antibody epitope effects Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555. Rappazzo 2021.0 https://doi.org/10.1126/science.abf4830 10.1126/science.abf4830 33495307 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23103 S477N,S514F NC_045512.2:g.1430G>A,NC_045512.2:g.1541C>T YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Ser514Phe , S S surface glycoprotein S antibody epitope effects While S477N itself is highly resistent to a broad range of monoclonal antibodies, combined with S514F high neutralization is restricted to only three antibodies in a broad screen. Liu 2020.0 https://doi.org/10.1101/2020.11.06.372037 10.1101/2020.11.06.372037 33442690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S T cell evasion Encouragingly, we find that the majority of T cell responses in recipients of two doses of the BNT162b2 vaccine are generated by epitopes that are invariant between the [wildtype] and two of the current variants of concern (B.1.1.7 and B.1.351). In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals and recipients of a only a single dose of mRNA vaccine – heterotypic neutralization dropped to negligible levels, particularly against B.1.351. Skelly 2021.0 https://doi.org/10.21203/rs.3.rs-226857/v1 10.21203/rs.3.rs-226857/v1 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S antibody epitope effects Resistent to some neutralizing antibodies: mAbs X593 and P2B-2F6 Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu S S surface glycoprotein S antibody epitope effects Resistent to some neutralizing antibodies: mAbs X593, 261-262, H4, and P2B-2F6 Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val S S surface glycoprotein S antibody epitope effects Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1 Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val S S surface glycoprotein S antibody epitope effects Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1 Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val S S surface glycoprotein S antibody epitope effects Resistent to some class 1 (Spike 'up' conformation) antibodies tested. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe S S surface glycoprotein S T cell evasion The induction level of IFN-gamma expression by the Y453F derivative in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456) was significantly lower. Motozono 2021.0 https://doi.org/10.1101/2021.04.02.438288 10.1101/2021.04.02.438288 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S T cell evasion L452R derivative virus did not induce IFN-gamma expression even at the highest concentration tested (10 nM) in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456). Motozono 2021.0 https://doi.org/10.1101/2021.04.02.438288 10.1101/2021.04.02.438288 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S antibody epitope effects Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding). Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S antibody epitope effects Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding). Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S antibody epitope effects Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1. Rappazzo 2021.0 https://doi.org/10.1126/science.abf4830 10.1126/science.abf4830 33495307 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S antibody epitope effects Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding). Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S antibody epitope effects Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1. Rappazzo 2021.0 https://doi.org/10.1126/science.abf4830 10.1126/science.abf4830 33495307 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G, YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys ,,,,, S S surface glycoprotein S antibody epitope effects N501Y substitution decreased the neutralizing and binding activities of CB6 and increased that of BD-23 Cheng 2021.0 https://doi.org/10.1186/s12985-021-01554-8 10.1186/s12985-021-01554-8 33910569 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn S S surface glycoprotein S antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His S S surface glycoprotein S T cell evasion Mutation is predicted to lose the T cell epitope for people carrying DRB1*0301 and DRB1*0401, but not for example in those who are DRB1*0701 or DRB1*1501 who would be predicted to show an enhanced response. This is also observed in a study of 26 each post-infection and post first dose HCWs. Reynolds 2021.0 https://doi.org/10.1126/science.abh1282 10.1126/science.abh1282 33931567 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val S S surface glycoprotein S antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S antibody epitope effects Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021.0 https://doi.org/10.1101/2020.11.03.367391 10.1101/2020.11.03.367391 33173867 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S antibody epitope effects Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg ,, S S surface glycoprotein S antibody epitope effects Massive reduction in binding efficiency vs wild type for mAbs CB6/LY-CoV16 and LY-CoV555. Rappazzo 2021.0 https://doi.org/10.1126/science.abf4830 10.1126/science.abf4830 33495307 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2:g.2492C>T YP_009724390.1:p.Ala831Val S S surface glycoprotein S antibody epitope effects Resistent to neutralizing mAb B38 Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S T cell evasion Analyzing responses to the E484K mutation seen in B.1.351 and P.1 variants, we noted that it did not fall in a region predicted to bind the HLAII alleles tested (table S4). The mutation appeared to have no substantial or differential impact on T cell responses. Reynolds 2021.0 https://doi.org/10.1126/science.abh1282 10.1126/science.abh1282 33931567 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22976 I472V NC_045512.2:g.1414A>G YP_009724390.1:p.Ile472Val S S surface glycoprotein S antibody epitope effects Resistent to neutralizing mAb X593 (on D614G background) Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22865 A435S NC_045512.2:g.1303G>T YP_009724390.1:p.Ala435Ser S S surface glycoprotein S antibody epitope effects Resistent to neutralizing mAb H014 (on D614G background) Li 2020.0 https://doi.org/10.1016/j.cell.2020.07.012 10.1016/j.cell.2020.07.012 32730807 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21597 S12F NC_045512.2:g.35C>T YP_009724390.1:p.Ser12Phe S S surface glycoprotein S antibody epitope effects A variant in low % circulation, predicted to have a similar effect to the experimentally verified S12P, which introduces a new signal peptide, altering cleavage to occur between residues C15 and V16, thereby eliminating the C15-C136 disulfide bond – similarly to escape mutants at positions C15 and C136. This in turn decreases to varying degrees N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8. McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe S S surface glycoprotein S antibody epitope effects "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S T cell evasion Vaccinated, but not post-infection sera, show decreased average T cell response to an N501Y peptide. When we primed transgenic mice expressing human HLA-DRB1*0401 with the Wuhan Hu-1 peptide pool, T cell responses to the B.1.1.7 variant peptide pool were significantly reduced (p = 0.0286). Furthermore, the T cell response to the spike N501Y mutation common to all three of the current VOC was ablated. Reynolds 2021.0 https://doi.org/10.1126/science.abh1282 10.1126/science.abh1282 33931567 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe S S surface glycoprotein S antibody epitope effects "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe S S surface glycoprotein S antibody epitope effects Ablates neutralization by N-terminal-domain-targeting mAbs 4-19. Impairs neutralization by N-terminal-domain-targeting mAbs 4A8 and 2-17. Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21969 C136Y NC_045512.2:g.407G>A YP_009724390.1:p.Cys136Tyr S S surface glycoprotein S antibody epitope effects Massively decreases N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8. McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22002 K147T NC_045512.2:g.440A>C YP_009724390.1:p.Lys147Thr S S surface glycoprotein S antibody epitope effects Massively decreases N terminal domain antigen recognition by supersite i mAbs S2M28, S2X28, S2X333, 4A8 (but not S2L28). McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S T cell evasion PBMCs of 11 mild COVID-19 patients collected 38-80 days after symptom onset were stimulated with the 15-mer peptide pools (w/ 10 residue overlaps) from the wholle viral proteome, showing no significant CD4+ cell count effect for P.1, and a slight increase in CD8+ percentage (p=0.0195) by Activation Induced Marker (AIM) assay (cellular immunity measurement). [in the text, this increase is not noted as signficant, even though p=0.05 is used elsewhere in the text as a signficance threshold] Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21998,21998 H146Y,H146Y ,NC_045512.2:g.436C>T YP_009724390.1:p.His146Tyr,YP_009724390.1:p.His146Tyr , S S surface glycoprotein S antibody epitope effects "Massive reduction in 4A8 monoclonal antibody EC50 (i.e. ablated recognition), but much milder effect on mAbs within antigenic supersite ""i""" McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22227 A222V NC_045512.2:g.665C>T YP_009724390.1:p.Ala222Val S S surface glycoprotein S antibody epitope effects "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317,22319,22320 D253G,D253G,D253G NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly ,, S S surface glycoprotein S antibody epitope effects "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22319 D253Y NC_045512.2:g.757G>T YP_009724390.1:p.Asp253Tyr S S surface glycoprotein S antibody epitope effects "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22323 S254F NC_045512.2:g.761C>T YP_009724390.1:p.Ser254Phe S S surface glycoprotein S antibody epitope effects "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." McCallum 2021.0 https://doi.org/10.1101/2021.01.14.426475 10.1101/2021.01.14.426475 33469588 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021.0 https://doi.org/10.1101/2021.01.06.20248960 10.1101/2021.01.06.20248960 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021.0 https://doi.org/10.1101/2021.01.06.20248960 10.1101/2021.01.06.20248960 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021.0 https://doi.org/10.1101/2021.01.06.20248960 10.1101/2021.01.06.20248960 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021.0 https://doi.org/10.1101/2021.01.06.20248960 10.1101/2021.01.06.20248960 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x) Shen 2021.0 https://doi.org/10.1101/2021.01.27.428516 10.1101/2021.01.27.428516 33532764 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021.0 https://doi.org/10.1101/2021.01.06.20248960 10.1101/2021.01.06.20248960 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22028,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 T95I,E156_R158delinsG,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.467_472del,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,, S S surface glycoprotein S syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this lineage defining mutation combination from B.1.617.3 increased syncytium formation ~2.3x. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala ,,, S S surface glycoprotein S reinfection Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection, evidenced by a reinfection hazard ratio of 2.39 (CI95: 1.88-3.11) relative to primary infection in the initial part of South Africa's 4th covid-19 wave (November 2021). In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. [minimal variant signature for Omicron (B.1.1.529) used based on H69del PCR dropout observed in November 2021 coincident with the rise of Omicron] Pulliam 2021.0 https://doi.org/10.1101/2021.11.11.21266068 10.1101/2021.11.11.21266068 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x) Shen 2021.0 https://doi.org/10.1101/2021.01.27.428516 10.1101/2021.01.27.428516 33532764 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects "Lowered the neutralization potency of mAb COVA1-12 to the limit of the assay. Decrease in potency was observed against the N501Y pseudotype for the cluster IX mAb COVA2-17." Rees-Spear 2021.0 https://doi.org/10.1101/2021.01.15.426849 10.1101/2021.01.15.426849 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp S S surface glycoprotein S antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant raises PIWAS epitope score from 3.6% to 6.2% (improved immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021.0 https://doi.org/10.1101/2021.01.06.20248960 10.1101/2021.01.06.20248960 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021.0 https://doi.org/10.1101/2021.01.06.20248960 10.1101/2021.01.06.20248960 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021.0 https://doi.org/10.1101/2021.01.06.20248960 10.1101/2021.01.06.20248960 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S antibody epitope effects This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic. Johnson 2020.0 https://doi.org/10.1101/2020.08.26.268854 10.1101/2020.08.26.268854 32869021 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021.0 https://doi.org/10.1101/2021.01.06.20248960 10.1101/2021.01.06.20248960 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S antibody epitope effects This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic. Johnson 2020.0 https://doi.org/10.1101/2020.08.26.268854 10.1101/2020.08.26.268854 32869021 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H ,NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His , S S surface glycoprotein S antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile S S surface glycoprotein S antibody epitope effects Not in a major wildtype epitope, mutant increases PIWAS epitope score from 0.69% to 2.3% Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021.0 https://doi.org/10.1101/2021.01.06.20248960 10.1101/2021.01.06.20248960 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S reinfection Three healthcare workers (29-50yo) had confirmed P.1 [Gamma] re-infection in the Amazonas region of Brazil 3-9 months after initial infection from viruses with distinct lineage from P.1, but mild symptoms upon re-infection and evidence for infectiousness during re-infection. Naveca 2021.0 https://doi.org/10.21203/rs.3.rs-318392/v1 10.21203/rs.3.rs-318392/v1 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala S S surface glycoprotein S antibody epitope effects Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021.0 https://doi.org/10.1101/2021.01.06.20248960 10.1101/2021.01.06.20248960 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His S S surface glycoprotein S antibody epitope effects Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021.0 https://doi.org/10.1101/2021.01.06.20248960 10.1101/2021.01.06.20248960 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S antibody epitope effects Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x). PG: these effects are laregly missing in the deletion-alone data Shen 2021.0 https://doi.org/10.1101/2021.01.27.428516 10.1101/2021.01.27.428516 33532764 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23401,23402,23403,23403 S477N,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S reinfection "11 cases of re-infection with the ""Marseille-4"" variant found within 1028 positive tests, where all of the earlier infections were from different strains. This lineage is also characterized by N:p.M234I;A376T" Fournier 2021.0 https://doi.org/10.1016/j.ijid.2021.03.068 10.1016/j.ijid.2021.03.068 33785459 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,23399,23401,23401,23402,23403,23403,23944,23944,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22894,22896,22898,23048,23521,23521,23522,23524,23524,23525,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,24130,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22673,22679,22679,22686,22992,21846,22992,22995,23202,21987,21990,23071,23071,23074,23074,23075,23075 A67V,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G446S,G446S,G446S,G496S,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N856K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,S371L,S373P,S373P,S375F,S477N,T95I,T478K,T478K,T547K,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H NC_045512.2:g.200C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2568C>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1640C>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy paired testing of vaccine sera against ancestral virus compared to Omicron BA.1 shows that 3-dose vaccine regimen provides over 50x fold increase in protection against Omicron(B.1.1.529 [BA.1]) compared to a 2-dose regimen. Hao 2022.0 https://doi.org/10.1101/2022.08.12.22278720 10.1101/2022.08.12.22278720 36032965 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg ,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Plasma neutralizing activity was also assessed against SARS-CoV-2 Delta, Omicron BA.1, BA.2 and BA.4/5 variants using viruses pseudotyped with appropriate variant spikeproteins. Delta breakthrough infection resulted in 15-fold increased neutralizing titers. Wang 2022.0 https://doi.org/10.1101/2022.08.11.503601 10.1101/2022.08.11.503601 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21987,21990,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23039,23040,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Omicron breakthrough infection after 3-dose vaccination resulted in a further 3.5-fold and 2.9-fold increase of Omicron BA.1 and BA.2 neutralizing titers. Omicron BA.4/5 showed the highest neutralization resistance of all variants tested, resulting in low geometric mean neutralizing titers in plasma samples obtained after the second vaccine dose (NT50=72). Wang 2022.0 https://doi.org/10.1101/2022.08.11.503601 10.1101/2022.08.11.503601 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg ,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Plasma neutralizing activity in 49 participants was measured using HIV-1 pseudotyped with the 100 WT SARS-CoV-2 spike protein. Delta breakthrough infection resulted in 11-fold increased geometric mean half-maximal neutralizing titer (NT50). Wang 2022.0 https://doi.org/10.1101/2022.08.11.503601 10.1101/2022.08.11.503601 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Log10ID50 of Beta neutralizing antibodies is 0.803x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022.0 https://doi.org/10.1101/2022.06.24.22276144 10.1101/2022.06.24.22276144 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882,23399,23401,23401,23402,23403,23403 N440K,N440K,N440K,N440K,N440K,N440K,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,, S S surface glycoprotein S reinfection A 47yo Indian male was reinfected with B.1.36 lineage virus in September 2020 after infection with genetically distinct B.1.36 virus in July, with negative PCR tests in between. While the forst episode was asymptomatic, the second included fever, cough, and malaise. The second case additionally contained stopgain ORF3a:E261* Rani 2021.0 https://doi.org/10.1002/jmv.26997 10.1002/jmv.26997 33818797 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg ,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Log10ID50 of Delta neutralizing antibodies is 0.872x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022.0 https://doi.org/10.1101/2022.06.24.22276144 10.1101/2022.06.24.22276144 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Log10ID50 of Omicron neutralizing antibodies is 0.722x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022.0 https://doi.org/10.1101/2022.06.24.22276144 10.1101/2022.06.24.22276144 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Log10ID50 of Beta neutralizing antibodies is 0.899x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022.0 https://doi.org/10.1101/2022.06.24.22276144 10.1101/2022.06.24.22276144 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg ,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Log10ID50 of Delta neutralizing antibodies is 0.952x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022.0 https://doi.org/10.1101/2022.06.24.22276144 10.1101/2022.06.24.22276144 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Log10ID50 of Omicron neutralizing antibodies is 0.686x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022.0 https://doi.org/10.1101/2022.06.24.22276144 10.1101/2022.06.24.22276144 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Values taken 28 days after booster dose was given for BBIBP-CorVvaccine to 390 participants with 130 participants in the 0-14d-10m, 0-21d-10m and 0-28d-10m group. The geometric mean titers (GMT) of neutralizing antibody in 0-28d-10m and 0-21d-10m group were significantly higher than 0-14d-10m group at month 3, month 6 and month 10 after the second dose. A sharply decrease by 4.85-fold (GMT: 94.4-20.3), 4.67-fold (GMT: 134.4-28.8) and 4.49-fold (GMT: 145.5-32.4) was observed from day 28 to month 10 after the second dose in 0-14d-10m, 0-21d-10m and 0-28d-10m group, respectively, and they had similar decline kinetics. Yao T 2022.0 https://doi.org/10.1101/2022.06.22.22276690 10.1101/2022.06.22.22276690 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg ,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Delta Variant B.1.617.2 RBD or w.t. SARS-CoV-2 RBD with nearly equal potency determined using Surrogate Viral Neutralization Tests. Uhal B 2022.0 https://doi.org/10.1101/2022.06.23.497326 10.1101/2022.06.23.497326 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Beta Variant B.1.351 RBD significantly better than w.t. SARS-CoV-2 RBD. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022.0 https://doi.org/10.1101/2022.06.23.497326 10.1101/2022.06.23.497326 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Alpha Variant B.1.1.7 RBD significantly better than GenScript IgG FL18-740 w.t. ACE-2 mAB. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022.0 https://doi.org/10.1101/2022.06.23.497326 10.1101/2022.06.23.497326 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Paradigms’ ACE-2 variant LVE/STR chimera binds to SARS-2 Omicron variant B.1.1.529 spike protein trimer with high affinity. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022.0 https://doi.org/10.1101/2022.06.23.497326 10.1101/2022.06.23.497326 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22188,23399,23401,23401,23402,23403,23403 I210del,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.629_631del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S reinfection A 42yo Iranian male was reinfected with B.1.36 lineage virus 128 days after infection with genetically distinct B.1.36 virus, with negative PCR tests in between. In the first instance patient presented with cough, headache, severe diarrhea. In the second instance symptoms were more severe: body pain, shortness of breath, headache and anosmia. Anti-SARS-CoV-2 IgG and IgM tests were negative after both episodes. [Non-seroconversion may be associated with elevated risk of re-infection] [I210del is a homoplasy that has appeared in several disparate parts of the global phylogenetic tree, including A and B lineages, primarily in LMICs] Salehi-Vaziri 2021.0 https://doi.org/10.1016/j.virusres.2021.198421 10.1016/j.virusres.2021.198421 33836204 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,23399,23401,23401,23402,23403,23403,23944,23944,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22894,22896,22898,23048,23521,23521,23522,23524,23524,23525,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,24130,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22673,22679,22679,22686,22992,21846,22992,22995,23202,21987,21990,23071,23071,23074,23074,23075,23075 A67V,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G446S,G446S,G446S,G496S,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N856K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,S371L,S373P,S373P,S375F,S477N,T95I,T478K,T478K,T547K,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H NC_045512.2:g.200C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2568C>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1640C>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 3.4-fold lower (95% CI: 3.2x-3.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022.0 https://doi.org/10.1101/2022.06.05.494889 10.1101/2022.06.05.494889 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21641,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22784,22785,22786,22786,22671,22672,22672,22673,22674,22679,22679,22686,22992,21594,21603,21603,21614,21617,21617,21618,21618,22992,22995,22194,22197,22198,22198,22199,22200,23071,23071,23074,23074,23075,23075 A27S,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,R408S,R408S,R408S,R408S,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T478K,T478K,V213G,V213G,V213G,V213G,V213G,V213G,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H NC_045512.2:g.79G>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 4.5-fold lower (95% CI: 4.3x-4.7x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022.0 https://doi.org/10.1101/2022.06.05.494889 10.1101/2022.06.05.494889 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21641,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,22811,22812,22813,22813,22813,22917,22879,22879,22881,22882,22882,22882,23060,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22784,22785,22786,22786,22671,22672,22672,22673,22674,22679,22679,22686,22992,23673,21594,21603,21603,21614,21617,21617,21618,21618,22992,22995,22194,22197,22198,22198,22199,22200,23071,23071,23074,23074,23075,23075 A27S,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,R408S,R408S,R408S,R408S,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,S704L,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T478K,T478K,V213G,V213G,V213G,V213G,V213G,V213G,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H NC_045512.2:g.79G>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.2111C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Ser704Leu,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 4.2-fold lower (95% CI: 5.8x-6.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022.0 https://doi.org/10.1101/2022.06.05.494889 10.1101/2022.06.05.494889 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22894,22896,22898,23521,23521,23522,23524,23524,23525,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22671,22672,22672,22673,22674,22679,22679,22686,22992,21846,22992,22995,21987,21990,23071,23071,23074,23074,23075,23075 A67V,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G446S,G446S,G446S,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,T95I,T478K,T478K,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H NC_045512.2:g.200C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 6.2-fold lower (95% CI: 11.8x-14.3x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022.0 https://doi.org/10.1101/2022.06.05.494889 10.1101/2022.06.05.494889 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22679,22679,24465,24466,24466,24468,24469,23521,23521,23522,23524,23524,23525,22194,22197,22198,22198,22199,22200,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21641,24421,24421,24422,24423,24424,24424,24424,23060,23062,23062,23063,23063,21594,21603,21603,21614,21617,21617,21618,21618,22879,22879,22881,22882,22882,22882,23595,23596,23596,23598,23599,23853,23854,23071,23071,23074,23074,23075,23075,23944,23944,23947,23948,23948,22992,22995,22671,22672,22672,22673,22674,22811,22812,22813,22813,22813,23018,22576,22577,22578,22784,22785,22786,22786,23604,23604,22686,22771,22775,22775,23053,23053,23054,23054,23055,23055,22992,23009,23010,23012,23013,23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 S373P,S373P,N969K,N969K,N969K,N969K,N969K,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,V213G,V213G,V213G,V213G,V213G,V213G,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A27S,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N501Y,N501Y,N501Y,N501Y,N501Y,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,N440K,N440K,N440K,N440K,N440K,N440K,N679K,N679K,N679K,N679K,N679K,N764K,N764K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D796Y,D796Y,D796Y,D796Y,D796Y,T478K,T478K,S371F,S371F,S371F,S371F,S371F,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,P681H,P681H,S375F,D405N,D405N,D405N,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.1117T>C,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.79G>T,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 13.0-fold lower (95% CI: 4.2x-4.6x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022.0 https://doi.org/10.1101/2022.06.05.494889 10.1101/2022.06.05.494889 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22679,22679,23039,23039,23040,24465,24466,24466,24468,24469,23521,23521,23522,23524,23524,23525,24130,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21641,24421,24421,24422,24423,24424,24424,24424,23060,23062,23062,23063,23063,22879,22879,22881,22882,22882,22882,23595,23596,23596,23598,23599,23853,23854,23071,23071,23074,23074,23075,23075,23202,23944,23944,23947,23948,23948,22992,22995,23048,22811,22812,22813,22813,22813,22673,22576,22577,22578,23604,23604,22686,23053,23053,23054,23054,23055,23055,22894,22896,22898,22992,23009,23010,23012,23013,24503,23399,23401,23401,23402,23403,23403 T95I,S373P,S373P,Q493R,Q493R,Q493R,N969K,N969K,N969K,N969K,N969K,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A27S,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N501Y,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,N440K,N440K,N679K,N679K,N679K,N679K,N679K,N764K,N764K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D796Y,D796Y,D796Y,D796Y,D796Y,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,S371L,G339D,G339D,G339D,P681H,P681H,S375F,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,G446S,G446S,G446S,S477N,E484A,E484A,E484A,E484A,L981F,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1478A>G,,NC_045512.2:g.1478A>G,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.79G>T,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.2941C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Leu981Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 4.4-fold lower (95% CI: 4.3x-4.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022.0 https://doi.org/10.1101/2022.06.05.494889 10.1101/2022.06.05.494889 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1336G>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1640C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2568C>A,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,NC_045512.2:g.2941C>T YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Omicron B.1.1.529 (BA.1) neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022.0 https://doi.org/10.1101/2022.06.01.494385 10.1101/2022.06.01.494385 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22784,22785,22786,22786,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.56C>T,NC_045512.2:g.56C>T,,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,NC_045512.2:g.71_79del,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,,NC_045512.2:g.638T>G,NC_045512.2:g.638T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Omicron BA.2 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022.0 https://doi.org/10.1101/2022.06.01.494385 10.1101/2022.06.01.494385 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23944,23944,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 A67V,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K NC_045512.2:g.200C>T,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.1112C>T,,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1112C>T,NC_045512.2:g.1117T>C,,NC_045512.2:g.1124C>T,NC_045512.2:g.1213G>A,,NC_045512.2:g.1213G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,,,NC_045512.2:g.1493A>G,,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2037T>G,,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,NC_045512.2:g.2037T>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2292C>A,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2862A>T,,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>T,NC_045512.2:g.2862A>C,,NC_045512.2:g.2862A>T,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A,,NC_045512.2:g.2907T>A,NC_045512.2:g.2907T>A YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Omicron BA.3 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022.0 https://doi.org/10.1101/2022.06.01.494385 10.1101/2022.06.01.494385 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Omicron BA.4 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022.0 https://doi.org/10.1101/2022.06.01.494385 10.1101/2022.06.01.494385 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S reinfection 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020. Possible reinfections were identified in 249 (0.7% [95% CI 0.6-0.8]) of 36509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Graham 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Omicron BA.5 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022.0 https://doi.org/10.1101/2022.06.01.494385 10.1101/2022.06.01.494385 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this RBD mutation conferred a 2.36x drop in neutralization (NT50). Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,23399,23401,23401,23402,23403,23403 E156_R158delinsG,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.467_472del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD mutation conferred a 4.85x drop in neutralization (NT50). Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 E156_R158delinsG,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.467_472del,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 7.42x drop in neutralization (NT50) [mostly from 3 of the sera]. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,23012,23399,23401,23401,23402,23403,23403 E156_R158delinsG,E484Q,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.467_472del,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 1.34x drop in neutralization (NT50) [mostly from a single serum]. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 E156_R158delinsG,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.467_472del,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x drop in neutralization (NT50) [working with the delins, less than just L452R but more than just E484Q]. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22028,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 T95I,E156_R158delinsG,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.467_472del,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this lineage defining mutation combination from B.1.617.3 conferred a ~11.8x drop in neutralization (NT50) [suggesting role for T19R and T95I in half the sera]. Mishra 2021.0 https://doi.org/10.1101/2021.10.04.463028 10.1101/2021.10.04.463028 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24410 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D950N NC_045512.2:g.284C>T,,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy "Using live B.1.621 virus and a cytopathic effect-based assay, sera from 37 Pfizer/BioNTech BNT162b2 vaccinees collected 10-20 days post-booster showed significantly lower (95) but still ""robust"" neutralization than against ancestral B.1 virus (107)." Messali 2021.0 https://doi.org/10.1002/jmv.27247 10.1002/jmv.27247 34329486 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H NC_045512.2:g.284C>T,,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Sera from vaccinees [ChAdOx1 and BNT162b2 primarily used in UK] shows decreased ability to neutralize B.1.621 compared to first wave virus and Alpha, with a magnitude of change similar to Beta. 2021.0 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24410 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D950N NC_045512.2:g.284C>T,,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Mean 7.6x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. [This is a greater reduction than Beta @ 6.3x] Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22227,23399,23401,23401,23402,23403,23403 A222V,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S reinfection 27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3). Both cases were mild. Second case also includes N:p.A220V Brehm 2021.0 https://doi.org/10.3390/v13040661 10.3390/v13040661 33921216 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21786,21786,21789,22298,22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403,24138 G75V,T76I,T76I,R246_D253delinsN,L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G,T859N NC_045512.2:g.224G>T,NC_045512.2:g.227C>T,NC_045512.2:g.227C>T,NC_045512.2:g.737_757del,NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2576C>A YP_009724390.1:p.Gly75Val,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Arg246_Asp253delinsAsn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr859Asn ,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Mean 1.7x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Mean 2.3x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Mean 2.6x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Mean 3.0x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Mean 6.3x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Mean 1.7x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021.0 https://doi.org/10.1101/2021.09.06.459005 10.1101/2021.09.06.459005 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In an Ontario long term care facility, cumulatively, weaker BNT162b2 vaccine stimulation, age/comorbidities, produced a ∼130-fold reduction in apparent neutralization titers in mean 88yo LTCH residents against Beta (B.1.351), relative to staff vaccinees against D614G wild type. 37.9% of 116 two-dose-mRNA-vaccinated residents had undetectable neutralizing antibodies to B.1.351. mRNA-1273 vaccinee sera displayed ~2 better neutralization than BNT162b2. [common defining B.1.351 mutations noted, as the manuscript does not provide details] Abe 2021.0 https://doi.org/10.1101/2021.08.06.21261721 10.1101/2021.08.06.21261721 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Relative to B.1, Kappa (B.1.617.1) shows mean 1.97x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021.0 https://doi.org/10.1101/2021.08.09.21261704 10.1101/2021.08.09.21261704 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22227,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Relative to B.1, Delta (B.1.617.2) shows mean 2.1x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021.0 https://doi.org/10.1101/2021.08.09.21261704 10.1101/2021.08.09.21261704 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021.0 https://doi.org/10.1101/2021.08.09.21261704 10.1101/2021.08.09.21261704 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S reinfection After a 128 day interval, a patient in Sao Paulo State, Brazil reinfected with P.1 (first episode likely predates P.1 emergence). Both cases were fairly mild (difficulty breathing, tiredness, dizziness and fatigue). Malta Romano 2021.0 https://doi.org/10.1590/S1678-9946202163036 10.1590/S1678-9946202163036 33909850 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800,22188,22206,22302,22335,22597,22597,22599,23011,23012,23521,23521,23522,23524,23524,23525,23604,23604 D80Y,I210del,D215G,Y248del,W258L,R346K,R346K,R346K,E484K,E484K,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H NC_045512.2:g.238G>T,NC_045512.2:g.629_631del,NC_045512.2:g.644A>G,NC_045512.2:g.743_745del,NC_045512.2:g.773G>T,,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,,NC_045512.2:g.1450G>A,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp80Tyr,YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Tyr248del,YP_009724390.1:p.Trp258Leu,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against A.VOI.V2 (first identified in Angola) reduced 8.0x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. Tada 2021.0 https://doi.org/10.1101/2021.05.14.444076 10.1101/2021.05.14.444076 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. Tada 2021.0 https://doi.org/10.1101/2021.05.14.444076 10.1101/2021.05.14.444076 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.4x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775 T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775,24863 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H,H1101D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.3301C>G YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.His1101Asp ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript] Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. [Mutation list in publication appears to contain a typo with R158del instead of R158G]" Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23664,23060,23062,23062,23063,23063,23011,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys ,,,,,,,,,,,,,, S S surface glycoprotein S reinfection Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission. Yinda 2021.0 https://doi.org/10.1101/2021.05.05.442780 10.1101/2021.05.05.442780 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22031,22033,23604 F157L,F157L,P681R NC_045512.2:g.469T>C,NC_045512.2:g.471C>A,NC_045512.2:g.2042C>G YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Pro681Arg ,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against A.23.1-v1 reduced 1.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22031,22033,23011,23012,23604 F157L,F157L,E484K,E484K,P681R NC_045512.2:g.469T>C,NC_045512.2:g.471C>A,,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg ,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against A.23.1-v2 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21717,21762,23011,23012,23399,23401,23401,23402,23403,23403,23593,23593,24224 Q52R,A67V,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,F888L NC_045512.2:g.155A>G,NC_045512.2:g.200C>T,,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T,NC_045512.2:g.2662T>C YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.525 reduced 4.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23399,23401,23401,23402,23403,23403 E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped viruses for B.1.618 was 2.7-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 3-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. Tada 2021.0 https://doi.org/10.1101/2021.05.14.444076 10.1101/2021.05.14.444076 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint] Tada 2021.0 https://doi.org/10.1101/2021.05.14.444076 10.1101/2021.05.14.444076 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint] Tada 2021.0 https://doi.org/10.1101/2021.05.14.444076 10.1101/2021.05.14.444076 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Detectable antibodies against B.1.351 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 71%, Day 209 54%. Detectable antibodies against B.1.351 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 79%, Day 209 58%. Detectable antibodies against B.1.351 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 63%, Day 43 100%, Day 119 71%, Day 209 79%. Decreased neutralization on some assays was seen especially in those vaccinees tested that were 71+. Pegu 2021.0 https://doi.org/10.1101/2021.05.13.444010 10.1101/2021.05.13.444010 34031659 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~3-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~10 fold with L242del] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were signficiant, but >100x weaker than in previously infected patients after first dose. Stamatatos 2021.0 https://doi.org/10.1126/science.abg9175 10.1126/science.abg9175 33766944 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~10-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~3 fold without the deletion] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were significant, but ~500x weaker than in previously infected patients after first dose. Stamatatos 2021.0 https://doi.org/10.1126/science.abg9175 10.1126/science.abg9175 33766944 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23664,23060,23062,23062,23063,23063,23011,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys ,,,,,,,,,,,,,, S S surface glycoprotein S reinfection Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission. Yinda 2021.0 https://doi.org/10.1101/2021.05.05.442780 10.1101/2021.05.05.442780 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021.0 https://doi.org/10.1101/2021.04.05.21254952 10.1101/2021.04.05.21254952 33851181 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021.0 https://doi.org/10.1101/2021.04.05.21254952 10.1101/2021.04.05.21254952 33851181 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021.0 https://doi.org/10.1101/2021.02.01.429069 10.1101/2021.02.01.429069 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021.0 https://doi.org/10.1101/2021.04.05.21254952 10.1101/2021.04.05.21254952 33851181 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021.0 https://doi.org/10.1101/2021.02.01.429069 10.1101/2021.02.01.429069 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021.0 https://doi.org/10.1101/2021.04.05.21254952 10.1101/2021.04.05.21254952 33851181 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021.0 https://doi.org/10.1101/2021.02.01.429069 10.1101/2021.02.01.429069 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23664,23060,23062,23062,23063,23063,23011,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys ,,,,,,,,,,,,,, S S surface glycoprotein S reinfection 4 health care workers in the 20's and 30's with no underlying conditions and seropositivity or confirmed 2020 SARS-CoV-2 infections were confirmed to have B.1.351 infection during a Februrary 2021 hospital outbreak in Luxembourg. Symptoms were mostly mild on first infection, and milder on second infection. Staub 2021.0 https://doi.org/10.2807/1560-7917.ES.2021.26.18.2100423 10.2807/1560-7917.ES.2021.26.18.2100423 33960291 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021.0 https://doi.org/10.1101/2021.04.05.21254952 10.1101/2021.04.05.21254952 33851181 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021.0 https://doi.org/10.1101/2021.02.01.429069 10.1101/2021.02.01.429069 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351. 2021.0 https://www.fda.gov/media/146217/download grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021.0 https://doi.org/10.1101/2021.04.05.21254952 10.1101/2021.04.05.21254952 33851181 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021.0 https://doi.org/10.1101/2021.02.01.429069 10.1101/2021.02.01.429069 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351. 2021.0 https://www.fda.gov/media/146217/download grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S reinfection Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion). Marquez 2021.0 https://doi.org/10.1017/ice.2021.195 10.1017/ice.2021.195 33934744 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer Solfrosi 2021.0 https://doi.org/10.1084/jem.20202756 10.1084/jem.20202756 33909009 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021.0 https://doi.org/10.1101/2021.04.05.21254952 10.1101/2021.04.05.21254952 33851181 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021.0 https://doi.org/10.1101/2021.02.01.429069 10.1101/2021.02.01.429069 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351. 2021.0 https://www.fda.gov/media/146217/download grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer Solfrosi 2021.0 https://doi.org/10.1084/jem.20202756 10.1084/jem.20202756 33909009 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy During an outbreak of SARS-CoV-2 501Y.V2 in a nursing home, all non-vaccinated residents (5/5) versus half of those fully vaccinated 2-5 weeks prior with BNT162b2 (13/26) were infected. Two of 13 vaccinated versus 4 of 5 non-vaccinated residents presented severe disease. BNT162b2 did not prevent the outbreak, but reduced transmission and disease severity. Among the 13 fully vaccinated residents who were infected, 2 (15.4%) presented with an asymptomatic disease, 9 (69.2%) developed mild to moderate symptoms, and 2 (15.4%) progressed to severe disease with fatal evolution secondary to acute respiratory distress syndrome (ARDS). There was no relationship between anti-S antibody levels at diagnosis and disease severity. Overall, the proportion of residents with severe disease in the non-vaccinated group (4/5) was higher than that in the vaccinated group (2/13). Only 1 vaccinated staff, but 10 unvaccinated were infected in the outbreak (no severe disease). Bailly 2021.0 https://doi.org/10.1093/cid/ciab446 10.1093/cid/ciab446 33993228 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S vaccine neutralization efficacy Neutralizing antibody titers of non-human primate sera after one or two doses of Ad26.COV2.S (Jannsen vaccine) against the variants containing the E484K substitution in the RBD were present but reduced (fold reduction between 3.35–7.78, 95% confidence interval all above twofold difference, one-sample t test). Solfrosi 2021.0 https://doi.org/10.1084/jem.20202756 10.1084/jem.20202756 33909009 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,23011,23012,23271,23399,23401,23401,23402,23403,23403,23604,23604,23948 T95I,E484K,E484K,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D796H NC_045512.2:g.284C>T,,NC_045512.2:g.1450G>A,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2386G>C YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp796His ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 51yo female with no severe COVID-19 risk factors tested positive 19 days after second dose of mRNA-1273 (Moderna) vaccine. Presented with sore throat, congestion, and headache developed; the next day she lost her sense of smell. Symptoms resolved over a one week period. Serum obtained 4 days after symptom onset was tested for neutralization against wild-type virus, the E484K mutant, and the B.1.526 variant. It was equally effective against each. These data suggest that the antibody response recognized these variants but was nonetheless insufficient to prevent a breakthrough infection. The virus detected matched neither B.1.1.7 nor B.1.526 VOC strains in wide circulation in New York at the time of infection, though shared some mutations. Hacisuleyman 2021.0 https://doi.org/10.1056/NEJMoa2105000 10.1056/NEJMoa2105000 33882219 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S reinfection Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion). Marquez 2021.0 https://doi.org/10.1017/ice.2021.195 10.1017/ice.2021.195 33934744 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22131,22220,22272,22299 T95I,R190T,F220I,R237K,R246T NC_045512.2:g.284C>T,NC_045512.2:g.569G>C,NC_045512.2:g.658T>A,NC_045512.2:g.710G>A,NC_045512.2:g.737G>C YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg190Thr,YP_009724390.1:p.Phe220Ile,YP_009724390.1:p.Arg237Lys,YP_009724390.1:p.Arg246Thr ,,,, S S surface glycoprotein S vaccine neutralization efficacy 65yo female with no severe Covid-19 risk factors tested positive 36 days after second dose of BNT162b2 (Pfizer) vaccine. Presented with fatigue, sinus congestion, and a headache developed; her symptoms plateaued and began to resolve six days later. [Mising genome coverage in regions of Spike covering clinically relevant mutations K417T, L452R, E484K, A701V, D796H, N501Y] Hacisuleyman 2021.0 https://doi.org/10.1056/NEJMoa2105000 10.1056/NEJMoa2105000 33882219 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22016,22017,23011,23012,23399,23401,23401,23402,23403,23403,23868 W152L,W152L,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,G769V ,NC_045512.2:g.455G>T,,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2306G>T YP_009724390.1:p.Trp152Leu,YP_009724390.1:p.Trp152Leu,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gly769Val ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The estimated vaccine effectiveness against R.1 strain SARS-CoV-2 infection among residents in a Kentucky skilled nursing facility was 66.2% (95% CI = 40.5%–80.8%) and among health care workers was 75.9% (95% CI = 32.5%–91.4%) in the cohort of only those 14d+ post-vaccination Pfizer booster dose. VE against symptomatic COVID-19 was 86.5% (95% CI = 65.6%–94.7%) among residents and 87.1% (95% CI = 46.4%–96.9%) among HCP. VE against hospitalization was 94.4% (95% CI = 73.9%–98.8%) among residents; no HCP were hospitalized. Three residents died, two of whom were unvaccinated (VE = 94.4%; 95% CI = 44.6%–99.4%). Cavanaugh 2021.0 https://doi.org/10.15585/mmwr.mm7017e2 10.15585/mmwr.mm7017e2 33914720 grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775,24863 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H,H1101D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.3301C>G YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.His1101Asp ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In a cluster of B.1.617[.1] infections related to travel from India to USA, one patient with mild symptoms had received their second dose of Pfizer vaccine more than two weeks before the infection [i.e. vaccine breakthrough]. Verghese 2021.0 https://doi.org/10.1128/JCM.00741-21 10.1128/JCM.00741-21 33952596 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Case 62541 cluster in Singapore included a fully vaccinated nurse 2 months post-vaccine [likely Pfizer based on dates and supply], and a doctor of unknown vaccine status. This cluster was caused by a B.1.617.2 virus [via crossreference to Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript] Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021.0 https://doi.org/10.1056/NEJMoa2103055 10.1056/NEJMoa2103055 33951374 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021.0 https://doi.org/10.1056/NEJMoa2103055 10.1056/NEJMoa2103055 33951374 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type). Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S reinfection Second infection in December 2020 with B.1.1.7 after April 2020 initial infection with B.2 in a 78-year-old man with a history of Type 2 diabetes mellitus, diabetic nephropathy on hemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnea, ischemic heart disease, with no history of immunosuppression. Harrington 2021.0 https://doi.org/10.1093/cid/ciab014 10.1093/cid/ciab014 33421056 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021.0 https://doi.org/10.1056/NEJMoa2103055 10.1056/NEJMoa2103055 33951374 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type). Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. Woldemeskel 2021.0 https://doi.org/10.1172/JCI149335 10.1172/JCI149335 33822770 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021.0 https://doi.org/10.1056/NEJMoa2103055 10.1056/NEJMoa2103055 33951374 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type). Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. Woldemeskel 2021.0 https://doi.org/10.1172/JCI149335 10.1172/JCI149335 33822770 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v2 reduced 7.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S vaccine neutralization efficacy E484K pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed a mean 2.8x decrease in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271 N501Y,N501Y,N501Y,N501Y,N501Y,A570D NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp ,,,,, S S surface glycoprotein S reinfection Partial sequencing of S gene reveals two cases of probable early 2021 B.1.1.7 lineage reinfection from non-B.1.1.7 original cases in Lombardy, with 45 to 90 days between infections (less than the typical 90 day guideline for this call). Patients were 56 and 58yo, immunocompenent, with one a former smoker with obesity and dyslipidemia. One case required intubation during first infection, but presented with mild symptoms upon reinfection. The other case convalesced at home during the first episode, but required CPAP support in the subacute clinical unit upon reinfection. Novazzi 2021.0 https://doi.org/10.1002/jmv.27066 10.1002/jmv.27066 33969504 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26767 I82T NC_045512.2:g.245T>C YP_009724393.1:p.Ile82Thr M M membrane glycoprotein M homoplasy This mutation presents mainly within the B.1 (44.0%) and B.1.525 (38.1%) lineages. Currently, 99.7% of the B.1.525 lineage isolates carry the M:I82T mutation. While this mutation is scattered across multiple phylogenetic clades, most cases cluster in two recent clades, suggesting a likely selective advantage in certain haplotype backgrounds. Shen 2021.0 https://doi.org/10.1080/22221751.2021.1922097 10.1080/22221751.2021.1922097 33896413 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26895 H125Y NC_045512.2:g.373C>T YP_009724393.1:p.His125Tyr M M membrane glycoprotein M homoplasy In experimental models of SARA_CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021.0 https://doi.org/10.1101/2021.05.19.444774 10.1101/2021.05.19.444774 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021.0 https://doi.org/10.1172/JCI149335 10.1172/JCI149335 33822770 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021.0 https://doi.org/10.1172/JCI149335 10.1172/JCI149335 33822770 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021.0 https://doi.org/10.1093/jtm/taab051 10.1093/jtm/taab051 33772577 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021.0 https://doi.org/10.1172/JCI149335 10.1172/JCI149335 33822770 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021.0 https://doi.org/10.1093/jtm/taab051 10.1093/jtm/taab051 33772577 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021.0 https://doi.org/10.1172/JCI149335 10.1172/JCI149335 33822770 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021.0 https://doi.org/10.1093/jtm/taab051 10.1093/jtm/taab051 33772577 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021.0 https://doi.org/10.1172/JCI149335 10.1172/JCI149335 33822770 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021.0 https://doi.org/10.1093/jtm/taab051 10.1093/jtm/taab051 33772577 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021.0 https://doi.org/10.1172/JCI149335 10.1172/JCI149335 33822770 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021.0 https://doi.org/10.1093/jtm/taab051 10.1093/jtm/taab051 33772577 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021.0 https://doi.org/10.1136/bmj.n1088 10.1136/bmj.n1088 33985964 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021.0 https://doi.org/10.1172/JCI149335 10.1172/JCI149335 33822770 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021.0 https://doi.org/10.1093/jtm/taab051 10.1093/jtm/taab051 33772577 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021.0 https://doi.org/10.1136/bmj.n1088 10.1136/bmj.n1088 33985964 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021.0 https://doi.org/10.1016/j.cmi.2021.05.007 10.1016/j.cmi.2021.05.007 33984489 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021.0 https://doi.org/10.1172/JCI149335 10.1172/JCI149335 33822770 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021.0 https://doi.org/10.1093/jtm/taab051 10.1093/jtm/taab051 33772577 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021.0 https://doi.org/10.1136/bmj.n1088 10.1136/bmj.n1088 33985964 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021.0 https://doi.org/10.1016/j.cmi.2021.05.007 10.1016/j.cmi.2021.05.007 33984489 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%. Pegu 2021.0 https://doi.org/10.1101/2021.05.13.444010 10.1101/2021.05.13.444010 34031659 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021.0 https://doi.org/10.1172/JCI149335 10.1172/JCI149335 33822770 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021.0 https://doi.org/10.1093/jtm/taab051 10.1093/jtm/taab051 33772577 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021.0 https://doi.org/10.1136/bmj.n1088 10.1136/bmj.n1088 33985964 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021.0 https://doi.org/10.1016/j.cmi.2021.05.007 10.1016/j.cmi.2021.05.007 33984489 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%. Pegu 2021.0 https://doi.org/10.1101/2021.05.13.444010 10.1101/2021.05.13.444010 34031659 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021.0 https://doi.org/10.2139/ssrn.3779160 10.2139/ssrn.3779160 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021.0 https://doi.org/10.21203/rs.3.rs-400230/v1 10.21203/rs.3.rs-400230/v1 33851150 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021.0 https://doi.org/10.1056/NEJMc2103022 10.1056/NEJMc2103022 33822491 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021.0 https://doi.org/10.1172/JCI149335 10.1172/JCI149335 33822770 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021.0 https://doi.org/10.1093/jtm/taab051 10.1093/jtm/taab051 33772577 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021.0 https://doi.org/10.1136/bmj.n1088 10.1136/bmj.n1088 33985964 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021.0 https://doi.org/10.1016/j.cmi.2021.05.007 10.1016/j.cmi.2021.05.007 33984489 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%. Pegu 2021.0 https://doi.org/10.1101/2021.05.13.444010 10.1101/2021.05.13.444010 34031659 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.2x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 and day 14 post-2nd dose) against a recombinant single variant virus (modified replicating WA-1 cDNA clone) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021.0 https://doi.org/10.1101/2021.02.02.21250799 10.1101/2021.02.02.21250799 33564782 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively. Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively. Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively. Dejnirattisai 2021.0 https://doi.org/10.1016/j.cell.2021.03.055 10.1016/j.cell.2021.03.055 33852911 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021.0 https://doi.org/10.1056/NEJMc2104036 10.1056/NEJMc2104036 33826815 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Detectable antibodies against P.1 at various time points using pseudovirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 85%. Pegu 2021.0 https://doi.org/10.1101/2021.05.13.444010 10.1101/2021.05.13.444010 34031659 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) with enrollment June 24 and November 9, 2020 from ~2000 HIV-negative 18-64 year olds (1:1 placebo to treatment), incidence of serious adverse events 14 or more days post- 2nd dose was balanced between the vaccine and placebo groups. A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed 3.5x reduction in neutralization (ID50) for B.1.351 RBD pseudotype HIB-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a similar 3.2x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera). Madhi 2021.0 https://doi.org/10.1056/NEJMoa2102214 10.1056/NEJMoa2102214 33725432 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera). Madhi 2021.0 https://doi.org/10.1056/NEJMoa2102214 10.1056/NEJMoa2102214 33725432 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23401,23402,23403,23403 P384L,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera). Madhi 2021.0 https://doi.org/10.1056/NEJMoa2102214 10.1056/NEJMoa2102214 33725432 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed for B.1.351 a CD4+ cell count decrease (29%, p=0.00063) as well as CD8+ (33%, p=0.0016) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S vaccine neutralization efficacy Human sera from 5 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) neutralized this variant 3.4x less relative to reference USA-WA1/2020 strain. 8 convalescent plasma with weak IgG ELISA titre neutralized this variant 2.4x less relative to reference USA-WA1/2020 strain. One plasma failed to neutralize at all. 11 convalescent plasma with moderate IgG ELISA titre neutralized this variant 4.2x less relative to reference USA-WA1/2020 strain. 11 convalescent plasma with high IgG ELISA titre neutralized this variant 2.6x less relative to reference USA-WA1/2020 strain. Jangra 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,22811,22812,22813,22813,22813,23011,23012 N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K,E484K NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys ,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In post-vaccination sera from individuals who received one (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) of the BNT162b2 Pfizer vaccine, an average 6.8x reduction in neutralization efficacy of this B.1.351 key variants pseudotype lentivirus vs D614G was observed. Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy This variant showed no change in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23399,23401,23401,23402,23403,23403 E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy This variant showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy This variant of key B.1.351 lineage mutations showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using a lentivirus virus pseudotyped with D614G Spike, sera from vaccinated individuals who received the second dose (9–11 days post-second dose of Pfizer) exhibited a robust neutralizing potential, with a mean NT50 value of 99,000. This was an average of a 2-fold increase, relative to sera drawn from the individuals who received one dose of vaccination—mean NT50 dilution of 51,300. Importantly, a 6-fold increase in mean NT50 dilution was obtained when sera from the first vaccination dose was compared to convalescent sera from cohort with severe disease (NT50 51,000 vs 8,700) 21 to 63 days post-onset. Kuzmina 2021.0 https://doi.org/10.1016/j.chom.2021.03.008 10.1016/j.chom.2021.03.008 33789085 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,24410 R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.472A>G,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Vaccination of health care workers in Delhi was started in early 2021, with the ChdOx-1 (Astra Zeneca) vaccine. Surveillance has suggested B.1.1.7 dominance in the Delhi area during early 2021, with growth of B.1.617 since March 2021. During the wave of infections during March and April an outbreak of SARS-CoV-2 was confirmed in 33 vaccinated staff members at a single tertiary centre (age 27-77 years). Sequencing revealed that 16/33 were B.1.617.2, with a range of other B lineage viruses including B.1.1.7 for the rest except one A lineage case. Importantly no severe cases were documented in this event. Ferreira 2021.0 https://doi.org/10.1101/2021.05.08.443253 10.1101/2021.05.08.443253 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012 L452R,L452R,L452R,L452R,L452R,L452R,E484Q ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln ,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484Q had a ~5x drop in neutralization (vs ~10x for E484K). When E484Q and L452R were combined, the fold change was significant, but similar to that of L452R alone (~2x), suggesting no evidence for an additive effect [perhaps even E484Q effect dilution]. Ferreira 2021.0 https://doi.org/10.1101/2021.05.08.443253 10.1101/2021.05.08.443253 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484K conferred a ten-fold reduction in neutralisation by vaccine sera. Ferreira 2021.0 https://doi.org/10.1101/2021.05.08.443253 10.1101/2021.05.08.443253 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. L452R conferred about a two-fold reduction in neutralisation by vaccine sera, but was not statistically significant with this sample size. Ferreira 2021.0 https://doi.org/10.1101/2021.05.08.443253 10.1101/2021.05.08.443253 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The sera of 16 individuals with time course collection was evaulated against VSV pseudotypes: neutralized D614G at week 2, whereas B.1.1.7 started to be neutralized at week 3, although less efficiently than D614G. B.1.1.7 and D614G strains were similarly neutralized at week 4 (1 week after booster dose). Planas 2021.0 https://doi.org/10.1038/s41591-021-01318-5 10.1038/s41591-021-01318-5 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose. Planas 2021.0 https://doi.org/10.1038/s41591-021-01318-5 10.1038/s41591-021-01318-5 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose. Planas 2021.0 https://doi.org/10.1038/s41591-021-01318-5 10.1038/s41591-021-01318-5 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy [Contrary to how this paper has been cited, Voysey et al. do NOT show evidence of decreased effectiveness of ChAdOx1 (AstraZeneca) against the South African B.1.351 lineage. Insufficient numbers reaching the primary study endpoint were available in that arm of the vaccine study to report any statistics from the South African participants. Additionally, the study period of the paper ended in November 2020, while the earliest reported case of this lineage is October (covariants.org), only becoming dominant by mid-November.] Voysey 2021.0 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21624,22022,22216,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24863 R21T,E154K,Q218H,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,H1101D NC_045512.2:g.62G>C,NC_045512.2:g.460G>A,NC_045512.2:g.654G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3301C>G YP_009724390.1:p.Arg21Thr,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Gln218His,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.His1101Asp ,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In 15 Pfizer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~3x (compared to ~11x for B.1.351). [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021.0 https://doi.org/10.1101/2021.05.04.442663 10.1101/2021.05.04.442663 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.1.7 lineage effectiveness was observed as 29.5% (95% CI [22.9,35.5]) against infection, and 54.1% against severe/critical/fatal disease (95% CI [26.1-71.9]). Two weeks or more after 2nd dose, effectiveness climbed to 89.5% [85.9,92.3] against infection, and 100% against severe/critical/fatal disease (95% CI [81.7,100]). Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.351 lineage effectiveness was observed as 16.9% (95% CI [10.4,23.0]) against infection, and 0% against severe/critical/fatal disease (95% CI [0-19.0]). Two weeks or more after 2nd dose, effectiveness climbed to 75.0% [70.5,78.9] against infection, and 100% against severe/critical/fatal disease (95% CI [73.7,100]). Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22915,22915,22916,22916,22917,22917,23060,23062,23062,23063,23063,23520,23521,23521,23522,23524,23524,23525,23944,23944,23947,23948,23948,25218 L18F,L452R,L452R,L452R,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,N501Y,A653V,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,D796Y,D796Y,D796Y,D796Y,D796Y,G1219V NC_045512.2:g.52C>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1958C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.2386G>T,NC_045512.2:g.2386G>T,,NC_045512.2:g.3656G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala653Val,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gly1219Val ,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 (Pfizer) vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains. Mallm 2021.0 https://doi.org/10.1101/2021.04.27.21254849 10.1101/2021.04.27.21254849 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23255,23257,23399,23401,23401,23402,23403,23403,25088 E484K,E484K,F565L,F565L,D614G,D614G,D614G,D614G,D614G,D614G,V1176F ,NC_045512.2:g.1450G>A,NC_045512.2:g.1693T>C,NC_045512.2:g.1695T>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Phe565Leu,YP_009724390.1:p.Phe565Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs] Sapkal 2021.0 https://doi.org/10.1101/2021.04.30.441559 10.1101/2021.04.30.441559 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23255,23257,23399,23401,23401,23402,23403,23403,25088 E484K,E484K,F565L,F565L,D614G,D614G,D614G,D614G,D614G,D614G,V1176F ,NC_045512.2:g.1450G>A,NC_045512.2:g.1693T>C,NC_045512.2:g.1695T>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Phe565Leu,YP_009724390.1:p.Phe565Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs] Sapkal 2021.0 https://doi.org/10.1101/2021.04.30.441559 10.1101/2021.04.30.441559 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23255,23257,23399,23401,23401,23402,23403,23403,25088 E484K,E484K,F565L,F565L,D614G,D614G,D614G,D614G,D614G,D614G,V1176F ,NC_045512.2:g.1450G>A,NC_045512.2:g.1693T>C,NC_045512.2:g.1695T>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Phe565Leu,YP_009724390.1:p.Phe565Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the P.1 & P.2 lineages of SARS-CoV-2 in Brazil. The Brazilian arm of the Phase 3 double blind study showed severe/critical disease VE of 81.9% (95% CI: 17.0-98.1), and moderate to severe/critical disease VE of 66.2% (95% CI: 51.0-77.1). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 69.3% of mostly severe infections sequenced as of this report, 69.4% were of P.2 lineage [defining lineage SNPs reported here]. 2021.0 https://www.fda.gov/media/146217/download grey literature Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021.0 https://doi.org/10.1101/2021.04.25.21256049 10.1101/2021.04.25.21256049 33948601 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021.0 https://doi.org/10.1101/2021.04.25.21256049 10.1101/2021.04.25.21256049 33948601 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.351 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021.0 https://doi.org/10.1126/science.abh1282 10.1126/science.abh1282 33931567 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021.0 https://doi.org/10.1101/2021.05.03.442455 10.1101/2021.05.03.442455 33972942 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021.0 https://doi.org/10.1101/2021.05.03.442455 10.1101/2021.05.03.442455 33972942 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v3 reduced 8.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 16.6% in this B.1.1.248 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021.0 https://doi.org/10.1101/2021.05.03.442455 10.1101/2021.05.03.442455 33972942 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021.0 https://doi.org/10.1126/science.abh1282 10.1126/science.abh1282 33931567 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021.0 https://doi.org/10.1126/science.abh1282 10.1126/science.abh1282 33931567 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021.0 https://doi.org/10.1101/2021.05.03.442455 10.1101/2021.05.03.442455 33972942 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021.0 https://doi.org/10.1126/science.abh1282 10.1126/science.abh1282 33931567 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021.0 https://doi.org/10.1101/2021.05.03.442455 10.1101/2021.05.03.442455 33972942 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy We observed a sharp decline in cases when ∼50% of the elderly population was 2 weeks beyond their first vaccination dose and at a time point during which the B.1.1.7 variant gained transmission dominance. In support of this finding, it was suggested that, after the first vaccination dose, more than 70% of patients develop neutralization antibodies,15 and the vaccine efficiency can reach 85%. Munitz 2021.0 https://doi.org/10.1016/j.xcrm.2021.100264 10.1016/j.xcrm.2021.100264 33899031 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021.0 https://doi.org/10.1101/2021.03.24.436620 10.1101/2021.03.24.436620 33791698 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021.0 https://doi.org/10.1101/2021.03.24.436620 10.1101/2021.03.24.436620 33791698 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.526 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021.0 https://doi.org/10.1101/2021.03.24.436620 10.1101/2021.03.24.436620 33791698 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021.0 https://doi.org/10.1101/2021.03.24.436620 10.1101/2021.03.24.436620 33791698 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%. Pegu 2021.0 https://doi.org/10.1101/2021.05.13.444010 10.1101/2021.05.13.444010 34031659 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021.0 https://doi.org/10.1101/2021.03.24.436620 10.1101/2021.03.24.436620 33791698 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%. Pegu 2021.0 https://doi.org/10.1101/2021.05.13.444010 10.1101/2021.05.13.444010 34031659 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23604,23604 D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy No significant change in virus neutralzation by 18 Pfizer two dose vaccinee sera compared to B.1.1.7. [results without including the used mutation A27S likely generalizable, as this is not a lineage defining mutation] Zuckerman 2021.0 https://doi.org/10.1101/2021.03.25.21253908 10.1101/2021.03.25.21253908 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using HIV pseudotype: Neutralization potency of 11 Moderna mRNA1273-elicited plasma (7-27 days post-2nd dose) was reduced ~2.8-fold compared to wildtype (D614G) S. It was reduced ~4-fold in 14 Pfizer/BioNtech BNT162b2-elicited plasma (7-27 days post-2nd dose). Using VSV pseudotype: we observed a 3-fold average reduction of Pfizer/BioNtech BNT162b2-elicited plasma neutralizing activity. McCallum 2021.0 https://doi.org/10.1101/2021.03.31.437925 10.1101/2021.03.31.437925 33821281 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021.0 https://doi.org/10.1101/2021.04.25.21256049 10.1101/2021.04.25.21256049 33948601 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021.0 https://doi.org/10.1101/2021.04.25.21256049 10.1101/2021.04.25.21256049 33948601 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021.0 https://doi.org/10.1101/2021.04.25.21256049 10.1101/2021.04.25.21256049 33948601 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies. Muik 2021.0 https://doi.org/10.1126/science.abg6105 10.1126/science.abg6105 33514629 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021.0 https://doi.org/10.1101/2021.04.25.21256049 10.1101/2021.04.25.21256049 33948601 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies. Muik 2021.0 https://doi.org/10.1126/science.abg6105 10.1126/science.abg6105 33514629 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x. Hoffman 2021.0 https://doi.org/10.1101/2021.05.04.442663 10.1101/2021.05.04.442663 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x. Hoffman 2021.0 https://doi.org/10.1101/2021.05.04.442663 10.1101/2021.05.04.442663 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose. Zhou 2021.0 https://doi.org/10.1101/2021.03.24.436620 10.1101/2021.03.24.436620 33791698 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x. Hoffman 2021.0 https://doi.org/10.1101/2021.05.04.442663 10.1101/2021.05.04.442663 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose. Zhou 2021.0 https://doi.org/10.1101/2021.03.24.436620 10.1101/2021.03.24.436620 33791698 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Vaccine elicited antibodies neutralized virus with the B.1.351 spike protein had an average 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Tada 2021.0 https://doi.org/10.1101/2021.02.05.430003 10.1101/2021.02.05.430003 33564768 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021.0 https://doi.org/10.1016/j.cell.2021.03.036 10.1016/j.cell.2021.03.036 33794143 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 1.15x *increase* in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization assays of B.1.1.7 virus showed a reduction of 2.5-fold (14 days post 2nd dose AstraZeneca, n=15), 2.1-fold (28 days post 2nd dose AstraZeneca, n=10), and 3.3-fold (7-17 days post 2nd dose Pfizer-BioNTech, n=25). [D1119H was included in the original paper, assumed typographical error and changed to D1118H] Supasa 2021.0 https://doi.org/10.1016/j.cell.2021.02.033 10.1016/j.cell.2021.02.033 33743891 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped D614G virus has reduced neutralization activity vs wild type: 1.2x (37 sera Pfizer median 9 days post 2nd dose, 37 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021.0 https://doi.org/10.1016/j.cell.2021.03.013 10.1016/j.cell.2021.03.013 33743213 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped B.1.1.7 virus has reduced neutralization activity vs wild type: 2.1x (30 sera Pfizer median 9 days post 2nd dose) and 2.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Note that Y145del was actually noted in the paper as the effect of their DNA construct, but this is equivalent at the protein level to the more commonly annotated Y144del. Garcia-Beltran 2021.0 https://doi.org/10.1016/j.cell.2021.03.013 10.1016/j.cell.2021.03.013 33743213 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920,23399,23401,23401,23402,23403,23403,25249,25249,25249 Y453F,D614G,D614G,D614G,D614G,D614G,D614G,M1229I,M1229I,M1229I NC_045512.2:g.1358A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.3687G>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile ,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped B.1.1.298 virus has reduced neutralization activity vs wild type: 1.4x (30 sera Pfizer median 9 days post 2nd dose) and 1.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021.0 https://doi.org/10.1016/j.cell.2021.03.013 10.1016/j.cell.2021.03.013 33743213 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021.0 https://doi.org/10.1016/j.cell.2021.03.013 10.1016/j.cell.2021.03.013 33743213 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021.0 https://doi.org/10.1016/j.cell.2021.03.013 10.1016/j.cell.2021.03.013 33743213 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort. Pegu 2021.0 https://doi.org/10.1101/2021.05.13.444010 10.1101/2021.05.13.444010 34031659 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021.0 https://doi.org/10.1016/j.cell.2021.03.013 10.1016/j.cell.2021.03.013 33743213 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort. Pegu 2021.0 https://doi.org/10.1101/2021.05.13.444010 10.1101/2021.05.13.444010 34031659 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.427/429 reduced 2.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23399,23401,23401,23402,23403,23403,25088 E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,V1176F ,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe ,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped P.2 virus has reduced neutralization activity vs wild type: 5.8x (30 sera Pfizer median 9 days post 2nd dose) and 2.9x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Garcia-Beltran 2021.0 https://doi.org/10.1016/j.cell.2021.03.013 10.1016/j.cell.2021.03.013 33743213 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021.0 https://doi.org/10.1101/2021.04.25.21256049 10.1101/2021.04.25.21256049 33948601 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021.0 https://doi.org/10.1101/2021.04.25.21256049 10.1101/2021.04.25.21256049 33948601 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped P.1 virus has reduced neutralization activity vs wild type: 6.7x (30 sera Pfizer median 9 days post 2nd dose) and 4.5x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Garcia-Beltran 2021.0 https://doi.org/10.1016/j.cell.2021.03.013 10.1016/j.cell.2021.03.013 33743213 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped B.1.351 v1 virus has reduced neutralization activity vs wild type: 34.5x (30 sera Pfizer median 9 days post 2nd dose) and 27.7x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021.0 https://doi.org/10.1016/j.cell.2021.03.013 10.1016/j.cell.2021.03.013 33743213 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped B.1.351 v2 virus has reduced neutralization activity vs wild type: 41.2x (30 sera Pfizer median 9 days post 2nd dose) and 20.8x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021.0 https://doi.org/10.1016/j.cell.2021.03.013 10.1016/j.cell.2021.03.013 33743213 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped B.1.351 v3 virus has reduced neutralization activity vs wild type: 42.4x (30 sera Pfizer median 9 days post 2nd dose) and 19.2x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021.0 https://doi.org/10.1016/j.cell.2021.03.013 10.1016/j.cell.2021.03.013 33743213 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021.0 https://doi.org/10.3390/v13040633 10.3390/v13040633 33917138 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001). Zhou 2021.0 http://doi.org/10.1016/j.cell.2021.02.037 10.1016/j.cell.2021.02.037 33730597 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001). Zhou 2021.0 http://doi.org/10.1016/j.cell.2021.02.037 10.1016/j.cell.2021.02.037 33730597 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination. Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001). Zhou 2021.0 http://doi.org/10.1016/j.cell.2021.02.037 10.1016/j.cell.2021.02.037 33730597 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination. Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy A two-dose regimen of (AstraZeneca) ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, vaccine efficacy against severe Covid-19 is undetermined. Madhi 2021.0 https://doi.org/10.1101/2021.02.10.21251247 10.1101/2021.02.10.21251247 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.351 sample. Contrast this with 1.4-fold reduction for just the pseudovirus combination of ""key"" B.1.351 mutations K417N+E484K+N501Y. WA1 and B.1.351 FRNT50 titers correlated weakly at the individual level, with some individual’s serum potently neutralizing WA1 while having FRNT50 for B.1.351 below the assay limit of detection (1:20)." Bates 2021.0 https://doi.org/10.1101/2021.04.04.21254881 10.1101/2021.04.04.21254881 33851185 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Observed 1.4-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.351 key variants lentivirus. Compare to 8.8-fold reduction against cultured B.1.351 virus. Bates 2021.0 https://doi.org/10.1101/2021.04.04.21254881 10.1101/2021.04.04.21254881 33851185 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S vaccine neutralization efficacy Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus. Bates 2021.0 https://doi.org/10.1101/2021.04.04.21254881 10.1101/2021.04.04.21254881 33851185 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S vaccine neutralization efficacy Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus. Bates 2021.0 https://doi.org/10.1101/2021.04.04.21254881 10.1101/2021.04.04.21254881 33851185 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S vaccine neutralization efficacy Human sera from 6 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) can neutralize both the reference USA-WA1/2020 strain and the mouse adapted SARS-CoV-2 strain that contains the N501Y spike mutation with similar efficiency. Rathnasinghe 2021.0 https://doi.org/10.1101/2021.01.19.21249592 10.1101/2021.01.19.21249592 33501468 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990,23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.1.7 sample. Contrast this with 1.3-fold reduction for just the pseudovirus combination of ""key"" B.1.1.7 mutation N501Y." Bates 2021.0 https://doi.org/10.1101/2021.04.04.21254881 10.1101/2021.04.04.21254881 33851185 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed. Collier 2021.0 https://doi.org/10.1038/s41586-021-03412-7 10.1038/s41586-021-03412-7 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed. Collier 2021.0 https://doi.org/10.1038/s41586-021-03412-7 10.1038/s41586-021-03412-7 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.7+E484K reduced 2.8x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Compare with 1.2x reduction for B.1.1.7 without E484K. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 20/29 sera after the first dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 variant of 3.2 ± 5.7. After the second dose, the GMT was markedly increased compared with the first-dose titres, with a fold change of 1.9 ± 0.9 (mean ± s.d.). Neutralization GMT of 27 subjects post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed. Collier 2021.0 https://doi.org/10.1038/s41586-021-03412-7 10.1038/s41586-021-03412-7 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pzifer vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1), but were all infected before 14 days post second vaccination. Kustin 2021.0 https://doi.org/10.1101/2021.04.06.21254882 10.1101/2021.04.06.21254882 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr ,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In 12 Moderna vaccinee sera 15 days post second dose (43 days since first vaccination), an average 2.8x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 4.8x decrease against the full P.1 type vs WA-1 was observed, though overall with a higher ID50 reciprocal value. In 10 Pfizer vaccinee sera 7 days or more post second dose (28 days or more since first vaccination), an average 2.2x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.8x decrease against the full P.1 type vs WA-1 was observed, with similar variant ID50 reciprocal value. Wang 2021.0 https://doi.org/10.1101/2021.03.01.433466 10.1101/2021.03.01.433466 33688656 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Wu 2021.0 https://doi.org/10.1101/2021.04.13.439482 10.1101/2021.04.13.439482 33880468 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Wu 2021.0 https://doi.org/10.1101/2021.04.13.439482 10.1101/2021.04.13.439482 33880468 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike). Riddell 2021.0 https://doi.org/10.1101/2021.04.17.440246 10.1101/2021.04.17.440246 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Wu 2021.0 https://doi.org/10.1101/2021.04.13.439482 10.1101/2021.04.13.439482 33880468 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike). Riddell 2021.0 https://doi.org/10.1101/2021.04.17.440246 10.1101/2021.04.17.440246 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>C,NC_045512.2:g.2031G>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In human sera 8 weeks post-vaccination with INO-4800, a ~7-fold reduction in B.1.351 neutralization was observed. Andrade 2021.0 https://doi.org/10.1101/2021.04.14.439719 10.1101/2021.04.14.439719 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23060,23062,23062,23063,23063 L452R,L452R,L452R,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The presence of these B.1.417/B.1.429 defining variants in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021.0 https://doi.org/10.1101/2021.04.14.21255431 10.1101/2021.04.14.21255431 33907767 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg ,,,,, S S surface glycoprotein S vaccine neutralization efficacy The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021.0 https://doi.org/10.1101/2021.04.14.21255431 10.1101/2021.04.14.21255431 33907767 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S vaccine neutralization efficacy The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021.0 https://doi.org/10.1101/2021.04.14.21255431 10.1101/2021.04.14.21255431 33907767 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using B.1.351 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021.0 https://doi.org/10.1101/2021.04.22.441007 10.1101/2021.04.22.441007 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021.0 https://doi.org/10.1101/2021.04.22.441007 10.1101/2021.04.22.441007 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021.0 https://doi.org/10.1101/2021.04.22.441007 10.1101/2021.04.22.441007 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed. Andrade 2021.0 https://doi.org/10.1101/2021.04.14.439719 10.1101/2021.04.14.439719 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021.0 https://doi.org/10.1101/2021.04.22.441007 10.1101/2021.04.22.441007 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed. Andrade 2021.0 https://doi.org/10.1101/2021.04.14.439719 10.1101/2021.04.14.439719 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Among 46,884 HCWs in Manaus, Brazil vaccinated with at least one dose of CoronaVac, a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%; 95% CI, 11.3 - 71.4) in the odds of symptomatic SARS-CoV-2 infection was observed during the period 14 days or more after receiving the first dose. Estimated vaccine effectiveness of at least one dose against any SARS-CoV-2 infection was 35.1% (95% CI, −6.6 - 60.5) in the same time period. Hitchlings 2021.0 https://doi.org/10.1101/2021.04.07.21255081 10.1101/2021.04.07.21255081 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Average 2x neutralization efficiency decrease against sera from 26 Phase II trial Covaxin (BBV152) vaccine recipents. Very similar to B.1.1.7 (~2x) in the same study, and the neutralization from 17 sera of natural infections across B1 lineages. Yadav 2021.0 https://doi.org/10.1101/2021.04.23.441101 10.1101/2021.04.23.441101 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 6 of 11 (55%) vaccine recipients (Moderna or Pfizer), showed 2x reduction in neutralization to a B.1.429 lineage virus. Deng 2021.0 https://doi.org/10.1101/2021.03.07.21252647 10.1101/2021.03.07.21252647 33758899 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403,24374,25135 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G,L938F,K1191N NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2812C>T,NC_045512.2:g.3573G>T YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu938Phe,YP_009724390.1:p.Lys1191Asn ,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for CAL.20C (B.1.429), and a slight decrease in CD8+ percentage (p=0.0201) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021.0 https://doi.org/10.1101/2021.02.27.433180 10.1101/2021.02.27.433180 33688655 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys , S S surface glycoprotein S vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, ELISA tests show 10x reduced efficacy of a majority of isolated antibodies, but only a modest decrease for vaccine plasma overall. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a modest decrease in neutralization by vaccine plasma was observed. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed. Wang 2021.0 https://doi.org/10.1101/2021.01.15.426911 10.1101/2021.01.15.426911 33501451 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In Moderna vaccinee sera, 2.7x reduction in neutralization, and 6.4 for the full B.1.351 Spike mutation complement, but despite the observed decreases, titers in human vaccinee sera against the B.1.351 variant remained at clinically significant level of ~1/300. Wu 2021.0 https://doi.org/10.1101/2021.01.25.427948 10.1101/2021.01.25.427948 33501442 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Vaccine plasma neutralization of B.1.351-spike virus was nominally robust but lower (~3x) than other variants of concern. Liu 2021.0 https://doi.org/10.1056/NEJMc2102017 10.1056/NEJMc2102017 33684280 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing] Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing] Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing] Wang 2021.0 https://doi.org/10.1038/s41586-021-03398-2 10.1038/s41586-021-03398-2 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021.0 https://doi.org/10.1101/2021.06.28.449914 10.1101/2021.06.28.449914 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy 3.2x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021.0 https://doi.org/10.1101/2021.08.04.455140 10.1101/2021.08.04.455140 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,,NC_045512.2:g.1250A>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe ,,,,,,,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralizing activity of vaccine was slightly lower against B.1.1.248 variant constellation in sera tested from most of the 15 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)] Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)] Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y ,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,,,, S S surface glycoprotein S vaccine neutralization efficacy In 20 sera from BNT162b2 mRNA vaccine inoculated participants, 6 displayed mild (2x) reductions in neutralization. This variant combination showed the highest reduction, but the magnitude of the differences was small compared to the >4x differences in HA-inhibition titers that have been used to signal potential need for a strain change in influenza vaccines. Xie 2021.0 https://doi.org/10.1038/s41591-021-01270-4 10.1038/s41591-021-01270-4 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990,23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604 Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His ,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy The neutralizing activity of vaccine was somewhat lower against B.1.1.7 in sera tested from most of the 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021.0 https://doi.org/10.1038/s41591-021-01294-w 10.1038/s41591-021-01294-w 33664494 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera. Shen 2021.0 https://doi.org/10.1101/2021.01.27.428516 10.1101/2021.01.27.428516 33532764 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera. Shen 2021.0 https://doi.org/10.1101/2021.01.27.428516 10.1101/2021.01.27.428516 33532764 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S vaccine neutralization efficacy NVX-CoV2373 [Novavax] vaccine in phase 3 trial was 89.7% (95% CI, 80.2-94.6) effective in preventing COVID-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8-99.5) and 86.3% (71.3-93.5) against the prototype strain and B.1.1.7 variant, respectively. Heath 2021.0 https://doi.org/10.1101/2021.05.13.21256639 10.1101/2021.05.13.21256639 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract. Planas 2021.0 https://doi.org/10.1038/s41591-021-01318-5 10.1038/s41591-021-01318-5 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,, S S surface glycoprotein S tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract. Planas 2021.0 https://doi.org/10.1038/s41591-021-01318-5 10.1038/s41591-021-01318-5 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22811,22812,22813,22813,22813,23011,23012,23060,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val ,,,,,,,,,,,,,,,,,,,,, S S surface glycoprotein S tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: while B.1.1.7 and D614G showed neutralization by nasal swab from only one different previously infected vacinee neutralizing at weeks 3 and 6, B.1.351 showed zero neutralization at either time point in any sample (and relatively impaired serum neutralization). Planas 2021.0 https://doi.org/10.1038/s41591-021-01318-5 10.1038/s41591-021-01318-5 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23401,23402,23403,23403 S477N,D614G,D614G,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly ,,,,,, S S surface glycoprotein S symptom prevalence Compared to the clade 20A strains that predominated during phase 1 between March and May 2020, the Marseille-4 variant (characterized by this mutation plus N:p.M234I;A376T) was associated with a lower frequency of cough, rhinitis, and olfactory and gustatory disorders. By contrast, hypoxemia was more frequent in patients infected with the Marseille-4 variant. Fournier 2021.0 https://doi.org/10.1016/j.ijid.2021.03.068 10.1016/j.ijid.2021.03.068 33785459 peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S symptom prevalence "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." van Loon 2021.0 https://doi.org/10.1101/2021.04.15.21255389 10.1101/2021.04.15.21255389 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S symptom prevalence "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." van Loon 2021.0 https://doi.org/10.1101/2021.04.15.21255389 10.1101/2021.04.15.21255389 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr ,,,, S S surface glycoprotein S symptom prevalence A higher proportion of cases infected with the B.1.1.7 variant were hypoxic on admission compared to other variants (70.0% vs 62.5%, p=0.029), in London between March 13th 2020 and February 17th 2021 (400 B.1.1.7 cases out of 1470 total sequenced). Snell 2021.0 https://doi.org/10.1101/2021.03.16.21253377 10.1101/2021.03.16.21253377 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23604 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,P681R ,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,,,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg ,,,,,,, S S surface glycoprotein S symptom prevalence Gross examination of 3+3 hamster lung specimens showed pronounced congestion and hemorrhages on days 5 and 7 post-infection in the case of the B.1.617.1 as compared with the B.1. The lung lesions with the B.1 variant were minimal to mild whereas with B.1.617.1 they were moderate. For B.1 pneumonic changes were minimal to mild (inflammatory cell infiltration, focal consolidation and mild congestion). The pronounced changes (moderate to severe) with mononuclear infiltration in the alveolar interstitial space, interstitial septal thickening, consolidation and pneumocyte hyperplasia were observed with B.1.617.1 variant consistently. Yadav 2021.0 https://doi.org/10.1101/2021.05.05.442760 10.1101/2021.05.05.442760 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22811,22812,22813,22813,22813,23664,23060,23062,23062,23063,23063,23011,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys ,,,,,,,,,,,,,, S S surface glycoprotein S symptom prevalence Inoculation with the B.1.351 isolate resulted in lower clinical scores in 6 rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. Our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity. Munster 2021.0 https://doi.org/10.1101/2021.05.07.443115 10.1101/2021.05.07.443115 34382034 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23709,23604,23604,24506,24914 N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,T716I,P681H,P681H,S982A,D1118H NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T,,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His ,,,,,,,,,,,,,,,, S S surface glycoprotein S tissue specific replication effects In this report, by using a lower infectious dose, we demonstrate that B.1.1.7 (cultured sample Hong Kong/HKPU-00015/2021) exhibits higher infectivity and/or replication efficiency in the nasal epithelium. (Hamster model of infection) Mok 2021.0 https://doi.org/10.1101/2021.04.19.440414 10.1101/2021.04.19.440414 not peer reviewed Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28854 S194L NC_045512.2:g.581C>T YP_009724397.2:p.Ser194Leu N N nucleocapsid phosphoprotein N homoplasy Mutation with a population frequency of 30% in a Mexican dataset, primarily of lineage 20B, but also present in a substantial number of 20A lineage sequences, suggesting convergent evolution. Barona-Gomez 2021.0 https://doi.org/10.1101/2021.05.18.21256128 10.1101/2021.05.18.21256128 not peer reviewed Paul Gordon Pokay From 41f8cc5066f8d743dcda3c10f045f49fdd14f2a8 Mon Sep 17 00:00:00 2001 From: Madeline Iseminger <32916719+miseminger@users.noreply.github.com> Date: Thu, 24 Oct 2024 17:12:15 -0700 Subject: [PATCH 072/161] Delete assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v2.0.tsv --- ...kay_functionalAnnotation_SARSCoV2_v2.0.tsv | 1944 ----------------- 1 file changed, 1944 deletions(-) delete mode 100644 assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v2.0.tsv diff --git a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v2.0.tsv b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v2.0.tsv deleted file mode 100644 index 249c92c4..00000000 --- a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v2.0.tsv +++ /dev/null @@ -1,1944 +0,0 @@ -"organism" "reference accession" "reference database name" "nucleotide position" "original mutation description" "nucleotide mutation" "amino acid mutation" "amino acid mutation alias" "gene name" "gene symbol" "protein name" "protein symbol" "measured variant functional effect" "inferred variant functional effect" "viral life cycle functional effect" "measured variant functional effect description" "CVX code" "DrugBank Accession Number" "Antibody Registry ID" "author" "publication year" "URL" "DOI" "PMID" "peer review status" "curator" "mutation functional annotation resource" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has an inhibition rate of virus production by Remdesivir of 0.80." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has a 0.27x fold change in EC50 value with Remdesivir." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "viral load" "" "" "This mutant causes a 0.48x fold change in the infectious virus production rate." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "viral load" "" "" "This mutant causes a 0.41x fold change in the infectious virus production rate." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has an inhibition rate of virus production by Remdesivir of 0.78." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has a 0.66x fold change in EC50 value with Remdesivir." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.526 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.8x reduction in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,22992,23011,23012,23664" "L5F,S477N,E484K,E484K,A701V" "" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 114 test-positive were Iota. Two dose vaccine efficacy against Iota was 95.7 (81.7-99.0%), one dose VE was 88.8 (0.7-98.7)%." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,25186" "L5F,Q1208H" "NC_045512.2:g.13C>T,NC_045512.2:g.3624G>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Gln1208His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Four of the convalescent sera tested showed 4-fold or greater improvement in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21587" "P9S" "NC_045512.2:g.25C>T" "YP_009724390.1:p.Pro9Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2M28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21597" "S12F" "NC_045512.2:g.35C>T" "YP_009724390.1:p.Ser12Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "A variant in low % circulation, predicted to have a similar effect to the experimentally verified S12P, which introduces a new signal peptide, altering cleavage to occur between residues C15 and V16, thereby eliminating the C15-C136 disulfide bond – similarly to escape mutants at positions C15 and C136. This in turn decreases to varying degrees N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600" "S13I" "NC_045512.2:g.38G>T" "YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The S13I mutation dampened binding of 5 mAbs and abrogated binding of 5 additional mAbs out of 11 neutralizing mAbs evaluated. Predicted to shift the signal peptide cleavage site from S13-Q14 to C15-V16, which can affect NTD conformation. PG: in saying S12F does not shift the signal peptide nor affect mAb binding, this manuscript appears to contradict the text of McCallum et al.'s earlier 2021 manuscript stating that S12F *does* affected some mAb binding via putative signal peptide shift." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018" "S13I,W152C" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The B.1.427/B.1.429 S13I/W152C NTD did not bind to any NTD-directed neutralizing mAbs, which are known to target a single antigenic site (antigenic site i), whereas binding of the non-neutralizing S2L20 mAb to the NTD antigenic site iv was not affected by any mutants, confirming proper retention of folding." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.249 (1.7-fold). Neutralization against 10 convalescent plasma was somewhat poorer (3.1-fold)." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 9 plasma collected 15 to 28 days after early 2020 infections, neutralization reduced 4.9-fold for B.1.427/B.1.429 compared to wildtype (D614G). In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.427/B.1.429 pseudotyped virus, as well as WT and other VOCs." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Swab samples N/NP viral RNA is approximately 2-fold higher in B.1.427/B.1.429 than in non-variant viruses." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using HIV pseudotype: Neutralization potency of 11 Moderna mRNA1273-elicited plasma (7-27 days post-2nd dose) was reduced ~2.8-fold compared to wildtype (D614G) S. It was reduced ~4-fold in 14 Pfizer/BioNtech BNT162b2-elicited plasma (7-27 days post-2nd dose). Using VSV pseudotype: we observed a 3-fold average reduction of Pfizer/BioNtech BNT162b2-elicited plasma neutralizing activity." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Antibody neutralization assays showed 6.7-fold resistance against 7/8 convalescent plasma." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Lineages bearing these spike mutations comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the ""California"" or ""West Coast"" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI:1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020." "" "" "" "Peng" "2021" "https://doi.org/10.1093/cid/ciab283" "doi:10.1093/cid/ciab283" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "14 of 34 RBD-specific mAbs showed reduced neutralization to the B.1.427/B.1.429 variant pseudotype." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.427/429 reduced 2.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 2.3x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "6 of 11 (55%) vaccine recipients (Moderna or Pfizer), showed 2x reduction in neutralization to a B.1.429 lineage virus." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 2.7x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403,25135" "S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G,K1191N" "" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys1191Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for CAL.20C (B.1.429), and a slight decrease in CD8+ percentage (p=0.0201) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21604,21604" "Q14H,Q14H" "NC_045512.2:g.42G>C,NC_045512.2:g.42G>T" "YP_009724390.1:p.Gln14His,YP_009724390.1:p.Gln14His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21605" "C15R" "NC_045512.2:g.43T>C" "YP_009724390.1:p.Cys15Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21606" "C15F" "NC_045512.2:g.44G>T" "YP_009724390.1:p.Cys15Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates neutralization by N-terminal-domain-targeting mAbs 4-19. Impairs neutralization by N-terminal-domain-targeting mAbs 4A8 and 2-17." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggetsing that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132" "L18F,T20N,P26S,D138Y,R190S" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The neutralization titer of NTD-binding mAb159 was 133-fold reduced on P.1 compared to Victoria (~wild type), with only 64% neutralization at 10 μg/mL. Residues 20, 18, and 138 form a cluster underlying the 245–259 loop, which inserts into a groove between the light and heavy chains of Fab 159. In addition, the N-terminal residues preceding residue 18 interact with the antibody and may be perturbed. Given that there is likely a single supersite (""i"") for potent NTD-binding antibodies, the binding of many of these are likely affected. Using 20 potent (primaruly anti-RBD) antibodies, neutralization was measured by a focus reduction neutralization test (FRNT) and compared with neutralization of Victoria (~wild type) and variants B.1.1.7 and B.1.351. Compared to Victoria neutralization by the mAbs was significantly impacted by P.1, with 12/20 showing > 10-fold reduction in FRNT50 titer and a number showing complete knockout of activity. The results with P.1 showed a greater impact compared to B.1.1.7 but were, as expected, similar to those with B.1.351." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In convalescent sera one month or more post-infection in Spring 2020, an average 6.5x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.4x decrease against the full P.1 type vs WA-1 was observed, with better full P.1 ID50 reciprocal value compared to the 10-mutation model." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Amongst RBD-targeting Emergency Use Authorized monoclonal antibody treatments CB6, LY-CoV555 and REGN10933 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1, but REGN10987 activity remains strong. RBD-targeting monoclonal antibodies 2-15 and C121 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. N terminal domain targeting monoclonal antibodies 5-7, 4-8, 4-18 and 2-17 have abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the “up” position." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 12 Moderna vaccinee sera 15 days post second dose (43 days since first vaccination), an average 2.8x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 4.8x decrease against the full P.1 type vs WA-1 was observed, though overall with a higher ID50 reciprocal value. In 10 Pfizer vaccinee sera 7 days or more post second dose (28 days or more since first vaccination), an average 2.2x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.8x decrease against the full P.1 type vs WA-1 was observed, with similar variant ID50 reciprocal value." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Gamma (P.1) variant is 0.6x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Three healthcare workers (29-50yo) had confirmed P.1 [Gamma] re-infection in the Amazonas region of Brazil 3-9 months after initial infection from viruses with distinct lineage from P.1, but mild symptoms upon re-infection and evidence for infectiousness during re-infection." "" "" "" "Naveca" "2021" "https://doi.org/10.21203/rs.3.rs-318392/v1" "doi:10.21203/rs.3.rs-318392/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "After a 128 day interval, a patient in Sao Paulo State, Brazil reinfected with P.1 (first episode likely predates P.1 emergence). Both cases were fairly mild (difficulty breathing, tiredness, dizziness and fatigue)." "" "" "" "Malta Romano" "2021" "https://doi.org/10.1590/S1678-9946202163036" "doi:10.1590/S1678-9946202163036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 4.1x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 349 test-positive were Gamma. Two dose vaccine efficacy against Gamma was 95.5 (90.9-97.8%), one dose VE was 74.2 (43.8-88.1%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x cleavage of S2 relative to WA1 (D614G) wildtype by Gamma variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but H655Y is upstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 3.0x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped P.1 virus has reduced neutralization activity vs wild type: 6.7x (30 sera Pfizer median 9 days post 2nd dose) and 4.5x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Unlike wild type or B.1.1.7, P.1 lineage virus was able to infect and replicate in common lab mouse strains, with high titer." "" "" "" "Montagutelli" "2021" "https://doi.org/10.1101/2021.03.18.436013" "doi:10.1101/2021.03.18.436013" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.248 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07. B.1.1.248 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.248 variant constellation in 10 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples, P=0.0020." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 16.6% in this B.1.1.248 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly lower against B.1.1.248 variant constellation in sera tested from most of the 15 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.7 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0039 for mild resistance." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Among 46,884 HCWs in Manaus, Brazil vaccinated with at least one dose of CoronaVac, a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%; 95% CI, 11.3 - 71.4) in the odds of symptomatic SARS-CoV-2 infection was observed during the period 14 days or more after receiving the first dose. Estimated vaccine effectiveness of at least one dose against any SARS-CoV-2 infection was 35.1% (95% CI, −6.6 - 60.5) in the same time period." "" "" "" "Hitchlings" "2021" "https://doi.org/10.1101/2021.04.07.21255081" "doi:10.1101/2021.04.07.21255081" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "VSV pseudotype P.1 entry mediated by the S proteins of the P.1 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Cell fusion proficiency was slight impaired. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.15x *increase* in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "VSV pseudotype P.1 showed 4.8-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections)." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Neutralizing antibodies that were generated following a mild infection with SARS-CoV-2 B.1.128 were effective in vitro, and likely protective, against the SARS-CoV-2 P.1. variant in the majority of individuals based on 60 convalescent sera tested." "" "" "" "Mendes-Correa" "2021" "https://doi.org/10.1101/2021.05.11.21256908" "doi:10.1101/2021.05.11.21256908" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype P.1 showed slight decrease in cell entry relative to wild type in 262T and 263T-ACE2 (kidney) cell lines. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for P.1 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the P.1 variants used, using the most popular as a stand in]" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "P.1 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with Lilly mAb combination LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of P.1. There was also escape from neutralization of P.1 by REGN10933 (one of 2 in Regeneron's mAb cocktail) and a modest reduction in neutralization of P.1 by AstraZeneca's AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized P.1 with all reaching a plateau at 100% neutralization; interestingly, ADG30 showed a slight increase of neutralization of P.1. S309 Vir was largely unaffected, although for several viruses, including P.1, the antibody failed to completely neutralize, conceivably reflecting incomplete glycosylation at N343, since the sugar interaction is key to binding of this antibody." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against P.1 at various time points using pseudovirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 85%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "PBMCs of 11 mild COVID-19 patients collected 38-80 days after symptom onset were stimulated with the 15-mer peptide pools (w/ 10 residue overlaps) from the wholle viral proteome, showing no significant CD4+ cell count effect for P.1, and a slight increase in CD8+ percentage (p=0.0195) by Activation Induced Marker (AIM) assay (cellular immunity measurement). [in the text, this increase is not noted as signficant, even though p=0.05 is used elsewhere in the text as a signficance threshold]" "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 256 for B.1.1.7 virus. Compare to somewhat stronger neutralization titer for wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "L18F,T20N,P26S,D138Y,R190S,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The relative transmissibility of P.1 estimated at the national level (Italy) varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. PG: variant list has been abbreviated due to mixed K417 bases in this lineage, potential miscalls of deletions" "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21801,22206,22334,22600,22600,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22986,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D80A,D215G,W258R,R346S,R346S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,A475V,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ala475Val,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments and mutations from variants of concern completely ablates neutralization in 19 of 21 convalescents plasma collected mean 1.3 months post infection. [actual Y145del from manuscript substituted with more common Y144del description]" "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801" "L18F,D80A" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The L18F and D80A of the B.1.351 lineage lead to reconfiguration of the N-terminal segment despite the disulfide between Cys16 and Cys136 that partly anchors the N-terminal peptide. The most consequential changes are probably from the triple residue deletion... which causes a shift of the nearby loop 144-155 and must also reconfigure the adjacent disorder loop (residues 246-260), both of which form part of the neutralizing epitopes...bringing large changes in the antigenic surface in this region." "" "" "" "Cai" "2021" "https://doi.org/10.1101/2021.04.13.439709" "doi:10.1101/2021.04.13.439709" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The 501Y.V2 to first wave IC50 ratio ranged from 6 to 200-fold. Averaging across all 7 participant convalescent sera highlighted the dramatic decrease in sensitivity to neutralization of authentic 501Y.V2 variants. PG: I'm purposefully ignoring D614G and A701V as contributors" "" "" "" "Cele" "2021" "https://doi.org/10.1038/s41586-021-03471-w" "doi:10.1038/s41586-021-03471-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike)." "" "" "" "Riddell" "2021" "https://doi.org/10.1101/2021.04.17.440246" "doi:10.1101/2021.04.17.440246" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike)." "" "" "" "Riddell" "2021" "https://doi.org/10.1101/2021.04.17.440246" "doi:10.1101/2021.04.17.440246" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~7-fold reduction in B.1.351 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pzifer vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1), but were all infected before 14 days post second vaccination." "" "" "" "Kustin" "2021" "https://doi.org/10.1101/2021.04.06.21254882" "doi:10.1101/2021.04.06.21254882" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 8 for B.1.351 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "A 1.8-fold drop in FRNT50 for B.1.351 was observed in 44 sera collected between 1 and 301 post-infection." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals (5/9) and recipients of a only a single dose of mRNA vaccine (10/11) – heterotypic neutralization dropped to negligible levels, particularly against B.1.351." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "B.1.351 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of B.1.351. There was also escape from neutralization of B.1.351 by REGN10933 and a modest reduction in neutralization of B.1.351 by AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized B.1.351." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed for B.1.351 a CD4+ cell count decrease (29%, p=0.00063) as well as CD8+ (33%, p=0.0016) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms had mean ~6x reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.054x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR22 molecule had a 1.57x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 0.036x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.351. We observed an increase (relative to D614G) in binding of soluble ACE2 to B.1.351, and to a much gearter extent to B.1.1.7, which both carry the N501Y mutation (see Fig 3)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: while B.1.1.7 and D614G showed neutralization by nasal swab from only one different previously infected vacinee neutralizing at weeks 3 and 6, B.1.351 showed zero neutralization at either time point in any sample (and relatively impaired serum neutralization)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "[Contrary to how this paper has been cited, Voysey et al. do NOT show evidence of decreased effectiveness of ChAdOx1 (AstraZeneca) against the South African B.1.351 lineage. Insufficient numbers reaching the primary study endpoint were available in that arm of the vaccine study to report any statistics from the South African participants. Additionally, the study period of the paper ended in November 2020, while the earliest reported case of this lineage is October (covariants.org), only becoming dominant by mid-November.]" "" "" "" "Voysey" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.07x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 8.2x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Sera from individuals who have been infected with Delta does not have strong neutralising activity against Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v2 reduced 7.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 6.3x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Pseudotype lentivirus for the full B.1.351 Spike variant list shows increase affinity for ACE2 as measured by IC50. This is in contrast to B.1.1.7 which showed no major change, indicating that the shared N501Y mutation is the driver of affinity change, attentuated in the B.1.1.7 mutatioon set, but maintained in the B.1.351 lineage." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v2 virus has reduced neutralization activity vs wild type: 41.2x (30 sera Pfizer median 9 days post 2nd dose) and 20.8x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Beta Variant B.1.351 RBD significantly better than w.t. SARS-CoV-2 RBD. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Encouragingly, we find that the majority of T cell responses in recipients of two doses of the BNT162b2 vaccine are generated by epitopes that are invariant between the [wildtype] and two of the current variants of concern (B.1.1.7 and B.1.351). In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals and recipients of a only a single dose of mRNA vaccine – heterotypic neutralization dropped to negligible levels, particularly against B.1.351." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.351 pseudotyped virus model ablates neutralization by RBD-directed mAbs CB6, 4-20, 2-4, 2-43, 910-30, 2-302-15, LY-Cov555, C121. B.1.351 pseudotyped virus model severely impairs neutralization by RBD-directed mAb 1-20. B.1.351 pseudotyped virus model impairs neutralization by RBD-directed mAb REGN10933. B.1.351 pseudotyped virus model ablates neutralization by N-terminal-domain-directed mAbs 5-24, 4-8, 4A8, 4-19. B.1.351 pseudotyped virus model severely impairs neutralization by N-terminal-domain-directed mAb 2-17. B.1.351 pseudotyped virus model impairs neutralization by N-terminal-domain-directed mAb 5-7. PG: Live virus data for the same mAbs is similar, but 1-20 becomes severally impaired, REGN10933 activity is ablated, and Brii-196 becomes impaired." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 16/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.351, with similar results for the live virus." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Beta neutralizing antibodies is 0.899x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "3.2x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Beta neutralizing antibodies is 0.803x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.351 sample. Contrast this with 1.4-fold reduction for just the pseudovirus combination of ""key"" B.1.351 mutations K417N+E484K+N501Y. WA1 and B.1.351 FRNT50 titers correlated weakly at the individual level, with some individual’s serum potently neutralizing WA1 while having FRNT50 for B.1.351 below the assay limit of detection (1:20)." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664,21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 6.7x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664,21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 99.7x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with all key mutations from B.1.351 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting some synergy between the mutations to decrease cell entry fitness (i.e. cell entry is liklely not the driver of this lineage's dominance)." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,23060,23061,23062,23062,23063,23063,22810,22810,22811,22812,22813,22813,22813,23011,23012,23399,23401,23401,23402,23403,23403" "L18F,D80A,D215G,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The most significant loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against authentic B.1.351 lineage virus (9.2-fold). Neutralization against 10 convalescent plasma was poorer (18.7x)." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks." "" "" "" "Meister" "2021" "https://doi.org/10.1093/infdis/jiab260" "doi:10.1093/infdis/jiab260" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Parana state of Brazil, patients aged 20-29 years experienced a tripling of their case fatality rate (CFR), from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling comparing February to January in 2021. Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil. [this is somewhat indirect evidence that assume greatly increasing proportion of P.1 cases in March (70%) compared to February, but the first official ID of P.1 in Parana state (Feb 16th) may be due to testing procedures rather than actual prevalence]" "" "" "" "Santos de Oliviera" "2021" "https://doi.org/10.1101/2021.03.24.21254046" "doi:10.1101/2021.03.24.21254046" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22915,22915,22916,22916,22917,22917,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "L18F,L452R,L452R,L452R,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 (Pfizer) vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains." "" "" "" "Mallm" "2021" "https://doi.org/10.1101/2021.04.27.21254849" "doi:10.1101/2021.04.27.21254849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22224,22227,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Delta (B.1.617.2) shows mean 2.1x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22224,22227,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Delta (B.1.617.2) shows 3.64x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "T19R,T95I,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this lineage defining mutation combination from B.1.617.3 conferred a ~4.5x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "T19R,T95I,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this lineage defining mutation combination from B.1.617.3 increased syncytium formation ~2.3x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "T19R,T95I,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this lineage defining mutation combination from B.1.617.3 conferred a ~11.8x drop in neutralization (NT50) [suggesting role for T19R and T95I in half the sera]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,23399,23401,23401,23402,23403,23403" "T19R,T95I,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22028,22915,22915,22916,22916,22917,22917,23604,23604,23399,23401,23401,23402,23403,23403,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,E156del,L452R,L452R,L452R,L452R,L452R,L452R,P681R,P681R,D614G,D614G,D614G,D614G,D614G,D614G,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4.5x cleavage of S2 relative to WA1 (D614G) wildtype by Delta (B.1.617.2) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~3.5x for closely related Kappa B.1.617.1 also with P681R at the cleavage site)." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. [Mutation list in publication appears to contain a typo with R158del instead of R158G]" "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Modelling the Delta variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increased 11x relative to wild type (15.3 vs 1.4). [del ~157 truncated due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a coinfection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 4.0x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.020x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.10x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 2.6x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In primary human airway epithelial cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 1.9x relative to wild type (2.7 vs 1.4). This is the Delta variant with the P681R furin cleavage site mutation absent. [del ~157 truncated due to ambiguity]" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Delta Variant B.1.617.2 RBD or w.t. SARS-CoV-2 RBD with nearly equal potency determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Delta neutralizing antibodies is 0.952x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Delta neutralizing antibodies is 0.872x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Plasma neutralizing activity was also assessed against SARS-CoV-2 Delta, Omicron BA.1, BA.2 and BA.4/5 variants using viruses pseudotyped with appropriate variant spikeproteins. Delta breakthrough infection resulted in 15-fold increased neutralizing titers." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Plasma neutralizing activity in 49 participants was measured using HIV-1 pseudotyped with the 100 WT SARS-CoV-2 spike protein. Delta breakthrough infection resulted in 11-fold increased geometric mean half-maximal neutralizing titer (NT50)." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 507 pM for binding to the Delta B.1.617.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001)." "" "" "" "Chia" "2021" "https://doi.org/10.1101/2021.07.28.21261295" "doi:10.1101/2021.07.28.21261295" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.92x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001)." "" "" "" "Chia" "2021" "https://doi.org/10.1101/2021.07.28.21261295" "doi:10.1101/2021.07.28.21261295" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccination of health care workers in Delhi was started in early 2021, with the ChdOx-1 (Astra Zeneca) vaccine. Surveillance has suggested B.1.1.7 dominance in the Delhi area during early 2021, with growth of B.1.617 since March 2021. During the wave of infections during March and April an outbreak of SARS-CoV-2 was confirmed in 33 vaccinated staff members at a single tertiary centre (age 27-77 years). Sequencing revealed that 16/33 were B.1.617.2, with a range of other B lineage viruses including B.1.1.7 for the rest except one A lineage case. Importantly no severe cases were documented in this event." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "The incidence rate of Covid-19 during the Delta-dominant period (Jul-Aug 2021) was lower for late vaccinated (49.0/1000 person-years) [formerly placebo] versus early vaccinated (77.1/1000 person-years) participants in the Moderna mRNA-1273 Phase 3 trials, representing a 36.4% VE reduction (95% CI 17.1%-51.5%). There were fewer severe Covid-19 cases in the late group (6; 6.2/1000 person-years) than early (13; 3.3/1000 person-years), representing a 46.0% reduction (95% CI −52.4%-83.2%). Three Covid-19 related hospitalizations occurred with two resulting deaths in the early group." "" "" "" "Baden" "2021" "https://doi.org/10.1101/2021.09.17.21263624" "doi:10.1101/2021.09.17.21263624" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance." "" "" "" "Twohig" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.89x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance." "" "" "" "Twohig" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Case 62541 cluster in Singapore included a fully vaccinated nurse 2 months post-vaccine [likely Pfizer based on dates and supply], and a doctor of unknown vaccine status. This cluster was caused by a B.1.617.2 virus [via crossreference to" "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Delta Molnupiravir (MK-4482) had ~4x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Denmark, for the period Jan 1 to Jun 27, 2021, Delta variant was associated with increased an risk ratio of 2.83 [95% CI 2.02–3.98] for hospitalization." "" "" "" "Bager" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.2 aka Delta) showed a 2.34x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Delta (B.1.617.2) has an IC50 fold change of 0.87x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Delta (B.1.617.2) has an IC50 fold change of 0.15x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Delta (B.1.617.2) has an IC50 fold change of 46.5x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Delta (B.1.617.2) has an IC50 fold change of 0.57x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Delta (B.1.617.2) variant is 0.6x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,23399,23401,23401,23402,23403,23403" "T19R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21627" "T22I" "NC_045512.2:g.65C>T" "YP_009724390.1:p.Thr22Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain, frequently observed in various human infection lineages, reduces the tropism of SARS-CoV-2 in F81 (cat kidney, Felis catus) and BHK-21 (golden hamster kidney, Mesocricetus auratus) cell line cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21648" "T29I" "NC_045512.2:g.86C>T" "YP_009724390.1:p.Thr29Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21717,21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23011,23012,23399,23401,23401,23402,23403,23403,23593,23593,24224" "Q52R,A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,F888L" "" "YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.525 reduced 4.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21717,23011,23012,23593,23593,24224" "Q52R,E484K,E484K,Q677H,Q677H,F888L" "" "YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The B.1.525 appears to have poor transmissibility when in competition with B.1.1.7 and other circulating strains in Denmark (early 2021)." "" "" "" "Albertsen" "2021" "https://www.covid19genomics.dk/2021-05-08_data-overview.html#b1525" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21752,21752" "W64R,W64R" "NC_045512.2:g.190T>A,NC_045512.2:g.190T>C" "YP_009724390.1:p.Trp64Arg,YP_009724390.1:p.Trp64Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21759" "H66R" "NC_045512.2:g.197A>G" "YP_009724390.1:p.His66Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent, especially on a D614 wildtype background." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Neutralization activity of almost all Moderna Phase 1 sera tested actually *increased*." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This deletion outside the receptor binding domain in pseudotyped VSV promoted the capacity of pseudotyped VSV to transduce black flying fox (Pteropus alecto) kidney PabKi.1 cells (17.8%) to a level twice that of human epithelial-like Huh-7 cells (9.8%)" "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No notable change in neutralization efficiency, despite N439K by itself showing a ~2x decrease on average in 16 health workers' convalescent sera." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduces neutralization by structurally unmapped mAb COVA1-21 (cluster XI)." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization activity of convalescent sera tested decreased ~2x with this B.1.1.7 pseudotyped virus." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization activity of almost all convalescent sera tested decreased ~2x." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "The delH69/V70 enhances viral infectivity, indicating its effect on virus fitness is independent to the N501Y RBM change [with which it is found in lineage B.1.1.7] Possibly arisen as a result of the virus evolving from immune selection pressure in infected individuals and possibly only one chronic infection in the case of lineage B.1.1.7." "" "" "" "Kemp" "2020" "https://doi.org/10.1101/2020.12.14.422555" "doi:10.1101/2020.12.14.422555" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was somewhat lower against B.1.1.7 in sera tested from most of the 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.7 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2489." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.1.7 sample. Contrast this with 1.3-fold reduction for just the pseudovirus combination of ""key"" B.1.1.7 mutation N501Y." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, much closer to D614G activity level than Y453F alone, suggesting compensatory effects between the deletion and the mutation in human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild to modest decrease in infection rate amongst the cells, suggesting a net mild negative effect on human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing moderate decrease in infection rate amongst the cells, significantly lower than the deletion or Y453F alone, or their combination, suggesting a synergistic effect on poorer human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920,23399,23401,23401,23402,23403,23403,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,D614G,D614G,D614G,D614G,D614G,D614G,M1229I,M1229I,M1229I" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.298 virus has reduced neutralization activity vs wild type: 1.4x (30 sera Pfizer median 9 days post 2nd dose) and 1.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from Mink Cluster 5 was neutralized more easily than D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with all key mutations from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (~50%) decrease in infection rate amongst the cells, suggesting that this anthropozoonotic event is driven by other factors at the expense of human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells, markedly higher infectivity than either mutation alone, suggesting a synergistic net neutral effect on human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23011,23012,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7+E484K reduced 2.8x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Compare with 1.2x reduction for B.1.1.7 without E484K." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23011,23012,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23011,23012,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization capacity GMT of 27 subjects' sera post-infection was markedly worse against B.1.1.7 + E484K than the lineage alone, with a 11.4x drop." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23011,23012,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." "" "" "" "van Loon" "2021" "https://doi.org/10.1101/2021.04.15.21255389" "doi:10.1101/2021.04.15.21255389" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, moreso than this combination with the addition of P681H." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "A higher proportion of cases infected with the B.1.1.7 variant were hypoxic on admission compared to other variants (70.0% vs 62.5%, p=0.029), in London between March 13th 2020 and February 17th 2021 (400 B.1.1.7 cases out of 1470 total sequenced)." "" "" "" "Snell" "2021" "https://doi.org/10.1101/2021.03.16.21253377" "doi:10.1101/2021.03.16.21253377" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation combination causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." "" "" "" "van Loon" "2021" "https://doi.org/10.1101/2021.04.15.21255389" "doi:10.1101/2021.04.15.21255389" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x). PG: these effects are laregly missing in the deletion-alone data" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively." "" "" "" "Schuit" "2021" "https://doi.org/10.1093/infdis/jiab171" "doi:10.1093/infdis/jiab171" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks." "" "" "" "Meister" "2021" "https://doi.org/10.1093/infdis/jiab260" "doi:10.1093/infdis/jiab260" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%)." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion)." "" "" "" "Marquez" "2021" "https://doi.org/10.1017/ice.2021.195" "doi:10.1017/ice.2021.195" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion)." "" "" "" "Marquez" "2021" "https://doi.org/10.1017/ice.2021.195" "doi:10.1017/ice.2021.195" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 2.6x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 1 (B.1.1.7) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Live virus was tested ex vivo in reconstituted brochial epithelium, and out competed wild type." "" "" "" "Touret" "2021" "https://doi.org/10.1101/2021.03.22.436427" "doi:10.1101/2021.03.22.436427" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "NTD-specific nAbs showed a substantial (3-450x) decrease in neutralization potency against the recently reported highly transmissible B.1.1.7 variant of concern, whereas RBD-specific nAbs were either unaffected or showed lower decreases in potency." "" "" "" "Graham" "2021" "https://doi.org/10.1016/j.immuni.2021.03.023" "doi:10.1016/j.immuni.2021.03.023" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2.5x cleavage of S2 relative to WA1 (D614G) wildtype by Alpha variant variant as measured by mass spectrometry of Vero-TMPRSS culture." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Modelling the Alpha variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 3.9x relative to wild type (5.4 vs 1.4). This is less efficient than Delta (11x vs wildtype using a P681R mutation instead). [del ~144 changed due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a co-infection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "clinical indicators" "" "" "After adjusting for the age factor, in a prospective Chinese cohort study B.1.1.7 variant infection (compared to B.1.140) was the risk factor for C-reactive protein (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), Serum amyloid A (0.011, 5.031, [1.459, 17.354]), Creatine Kinase (0.034, 4.34, [0.05, 0.91]), CD4+ T lymphocyte (0.029, 3.31, [1.13, 9.71]), and Ground Glass Opacity (0.005, 5.418, [1.656, 17.729])" "" "" "" "Song" "2021" "https://doi.org/10.1101/2021.05.04.21256655" "doi:10.1101/2021.05.04.21256655" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 2/20 (10%) samples showed >10x reduction (sera collected ~1mo post Jan 2020 first wave in China). Neutralizing antibody titers of 8/20 samples (40%) decreased below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.7 pseudotyped virus model impairs binding by RBD-directed mAb 910-30. B.1.1.7 pseudotyped virus model abolishes N-terminal-domain-directed mAbs 5-24, 4-8, and 4A8. B.1.1.7 pseudotyped virus model impairs binding by N-terminal-domain-directed mAbs 2-17, 4-19, 5-7." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Lessens the potency of mAbs COVA2-17 (~5x, similar to N501Y alone), COVA1-12 (~11x) and COVA1-21 (>100x), which do not compete allosterically." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Alpha Variant B.1.1.7 RBD significantly better than GenScript IgG FL18-740 w.t. ACE-2 mAB. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20x resistence to mAb CQ038 by B.1.1.7 pseudotyped virus" "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 1.7x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.1.7. We observed a dramatic increase (relative to D614G) in binding of soluble ACE2 to B.1.1.7, and to a lesser extent to B.1.351, which both carry the N501Y mutation (see Fig 3)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020. Possible reinfections were identified in 249 (0.7% [95% CI 0.6-0.8]) of 36509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants." "" "" "" "Graham" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM for binding to the Alpha B1.1.7. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively." "" "" "" "Schuit" "2021" "https://doi.org/10.1093/infdis/jiab171" "doi:10.1093/infdis/jiab171" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Second infection in December 2020 with B.1.1.7 after April 2020 initial infection with B.2 in a 78-year-old man with a history of Type 2 diabetes mellitus, diabetic nephropathy on hemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnea, ischemic heart disease, with no history of immunosuppression." "" "" "" "Harrington" "2021" "https://doi.org/10.1093/cid/ciab014" "doi:10.1093/cid/ciab014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "aerosolization" "" "" "Alpha variant cases in a large campus study showed fine-aerosol shedding amongst unmasked participants remained significantly greater for alpha variant infections (18-fold, 95% CI, 3.4 to 92-fold) after adjusting for the increased viral RNA in MTS and saliva, the number of coughs during sampling sessions, and symptom. After controlling for the effect of masks and numbers of coughs during sampling, alpha variant infection was associated with a 100-fold (95% CI, 16 to 650-fold) increase in coarse- and a 73-fold (95% CI, 15 to 350-fold) increase in fine-aerosol RNA shedding." "" "" "" "Adenaiye" "2021" "https://doi.org/10.1093/cid/ciab797" "doi:10.1093/cid/ciab797" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "First documented cases of domestic cat and dog infections with the B.1.1.7 strain." "" "" "" "Hamer" "2021" "https://doi.org/10.1111/tbed.14122" "doi:10.1111/tbed.14122" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaulated against VSV pseudotypes: neutralized D614G at week 2, whereas B.1.1.7 started to be neutralized at week 3, although less efficiently than D614G. B.1.1.7 and D614G strains were similarly neutralized at week 4 (1 week after booster dose)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Alpha Molnupiravir (MK-4482) had ~2.75x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM analysis of B.1.1.7 demonstrates an increased propensity for 'up', receptor accessible conformation of the Spike protein trimer." "" "" "" "Cai" "2021" "https://doi.org/10.1101/2021.04.13.439709" "doi:10.1101/2021.04.13.439709" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "NVX-CoV2373 [Novavax] vaccine in phase 3 trial was 89.7% (95% CI, 80.2-94.6) effective in preventing COVID-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8-99.5) and 86.3% (71.3-93.5) against the prototype strain and B.1.1.7 variant, respectively." "" "" "" "Heath" "2021" "https://doi.org/10.1101/2021.05.13.21256639" "doi:10.1101/2021.05.13.21256639" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the 47D10. Alpha (B.1.1.7) has an IC50 fold change of 0.40x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.44x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Alpha (B.1.1.7) has an IC50 fold change of 1.19x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.39x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 virus has reduced neutralization activity vs wild type: 2.1x (30 sera Pfizer median 9 days post 2nd dose) and 2.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Note that Y145del was actually noted in the paper as the effect of their DNA construct, but this is equivalent at the protein level to the more commonly annotated Y144del." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization assays of B.1.1.7 virus showed a reduction of 2.5-fold (14 days post 2nd dose AstraZeneca, n=15), 2.1-fold (28 days post 2nd dose AstraZeneca, n=10), and 3.3-fold (7-17 days post 2nd dose Pfizer-BioNTech, n=25). [D1119H was included in the original paper, assumed typographical error and changed to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We observed a sharp decline in cases when ∼50% of the elderly population was 2 weeks beyond their first vaccination dose and at a time point during which the B.1.1.7 variant gained transmission dominance. In support of this finding, it was suggested that, after the first vaccination dose, more than 70% of patients develop neutralization antibodies,15 and the vaccine efficiency can reach 85%." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Alpha (B.1.1.7) variant is 1.0x fold the wildtype in 42 COVI." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.1.7 lineage effectiveness was observed as 29.5% (95% CI [22.9,35.5]) against infection, and 54.1% against severe/critical/fatal disease (95% CI [26.1-71.9]). Two weeks or more after 2nd dose, effectiveness climbed to 89.5% [85.9,92.3] against infection, and 100% against severe/critical/fatal disease (95% CI [81.7,100])." "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,24506" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,S982A" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Lilly's LY-CoV16 showed marked reduction in neutralization of B.1.1.7." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Sera neutralized the B1.1.7 isolate with a lower potency (2-fold; 95% CL: 1.5 – 3-fold), and those with the lowest homotypic neutralizing potency had undetectable heterotypic potency (2/25)." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23709,23604,23604,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,T716I,P681H,P681H,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific replication effects" "" "" "In this report, by using a lower infectious dose, we demonstrate that B.1.1.7 (cultured sample Hong Kong/HKPU-00015/2021) exhibits higher infectivity and/or replication efficiency in the nasal epithelium. (Hamster model of infection)" "" "" "" "Mok" "2021" "https://doi.org/10.1101/2021.04.19.440414" "doi:10.1101/2021.04.19.440414" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7." "" "" "" "Graham" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization capacity GMT of 27 subjects' sera post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The mortality hazard ratio associated with infection with [B.1.1.7] compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community (54906 matched pairs of participants who tested positive for SARS-CoV-2 in pillar 2 between 1 October 2020 and 29 January 2021). In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases." "" "" "" "Challen" "2021" "https://doi.org/10.1136/bmj.n579" "doi:10.1136/bmj.n579" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7." "" "" "" "Graham" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036)." "" "" "" "Song" "2021" "https://doi.org/10.1101/2021.05.04.21256655" "doi:10.1101/2021.05.04.21256655" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies." "" "" "" "Muik" "2021" "https://doi.org/10.1126/science.abg6105" "doi:10.1126/science.abg6105" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies." "" "" "" "Muik" "2021" "https://doi.org/10.1126/science.abg6105" "doi:10.1126/science.abg6105" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "20/29 sera after the first dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 variant of 3.2 ± 5.7. After the second dose, the GMT was markedly increased compared with the first-dose titres, with a fold change of 1.9 ± 0.9 (mean ± s.d.). Neutralization GMT of 27 subjects post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype B.1.1.7 showed no significant difference in cell entry relative to wild type in 6 cell lines. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020, Rt of B.1.1.7 was 1.35x (95% CI 1.02-1.69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant." "" "" "" "Graham" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Slight neutralization improvement on average in 16 health workers' convalescent sera." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, but to a smaller extent than N501Y and the deletion alone." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "These key B.1.1.7 mutations as a combination neutralized slightly less well than D614G and this was noticeable in the lack of sera with high neutralizing titer for the viruses across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22679,22679,23521,23521,23522,23524,23524,23525,23525,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,23060,23061,23062,23062,23063,23063,22879,22879,22881,22882,22882,22882,23071,23071,23074,23074,23075,23075,22992,22995,22810,22810,22811,22812,22813,22813,22813,23018,22576,22577,22578,22783,22783,22784,22785,22786,22786,23604,23604,22686,23053,23053,23054,23054,23055,23055,22992,23009,23010,23012,23013,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,S373P,S373P,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,R408S,P681H,P681H,S375F,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 13.0-fold lower (95% CI: 4.2x-4.6x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22679,22679,23521,23521,23522,23524,23524,23525,23525,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,23060,23061,23062,23062,23063,23063,22879,22879,22881,22882,22882,22882,23071,23071,23074,23074,23075,23075,22992,22995,22810,22810,22811,22812,22813,22813,22813,23018,22576,22577,22578,22783,22783,22784,22785,22786,22786,23604,23604,22686,23053,23053,23054,23054,23055,23055,22992,23009,23010,23012,23013,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,S373P,S373P,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,R408S,P681H,P681H,S375F,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 17.2x-fold lower (95% CI: 0.6x-0.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,22810,22810,22811,22812,22813,22813,22813,23009,23010,23012,23013" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484A,E484A,E484A,E484A" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario, using a retrospective matched case (age, gender and onset date) study of 6,312 Omicron cases vs 8,875 Delta, the adjusted risk of hospitalization or death was 54% lower (HR=0.46, 95%CI: 0.27, 0.77) among Omicron cases, after adjusting for vaccination statis and time since 2nd shot. The ratio for >60yo was 0.55 (95%CI: 0.28-1.06), and <60yo was 0.30 (95%CI: 0.16-0.57)." "" "" "" "Ulloa" "2021" "https://doi.org/10.1101/2021.12.24.21268382" "doi:10.1101/2021.12.24.21268382" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23009,23010,23012,23013" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,E484A,E484A,E484A,E484A" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection, evidenced by a reinfection hazard ratio of 2.39 (CI95: 1.88-3.11) relative to primary infection in the initial part of South Africa's 4th covid-19 wave (November 2021). In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. [minimal variant signature for Omicron (B.1.1.529) used based on H69del PCR dropout observed in November 2021 coincident with the rise of Omicron]" "" "" "" "Pulliam" "2021" "https://doi.org/10.1101/2021.11.11.21266068" "doi:10.1101/2021.11.11.21266068" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21987,21990,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23039,23040,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron (a.k.a. B.1.1.529) Spike pseudotyped VSV and Vero E6 cells has somewhat reduced neutralization (2.7x) vs wild type with monoclonal antibody Sotrovimab (a.k.a. VIR-7831). [delins at 214 omitted for syntax compatibility]" "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21987,21990,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23039,23040,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron breakthrough infection after 3-dose vaccination resulted in a further 3.5-fold and 2.9-fold increase of Omicron BA.1 and BA.2 neutralizing titers. Omicron BA.4/5 showed the highest neutralization resistance of all variants tested, resulting in low geometric mean neutralizing titers in plasma samples obtained after the second vaccine dose (NT50=72)." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron (B.1.1.529 [BA.1]) have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "All 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 729 NT50." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "All 10 individuals with 3 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 3319 NT50." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Omicron BA.1 variant is 1.0x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Omicron BA.1 has an IC50 fold change of 1.26x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Delta variant and was used to determine neutralizing antibodytitres. There was a 24.63x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 4.21x fold increase in antibody response pre-reinfection. There was a 39.27x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.1 has an IC50 fold change of 0.08x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Omicron variant and was used to determine neutralizing antibodytitres. There was a 114.84x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 6.61x fold increase in antibody response pre-reinfection. There was a 1194.9x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against B.1 variant and was used to determine neutralizing antibodytitres. There was a 6.76x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 2.06x fold increase in antibody response pre-reinfection. There was a 8.18x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Omicron BA.1 has an IC50 fold change of 0.38x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron B.1.1.529 (BA.1) neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 73 pM for binding to the Omicron B.1.1.529. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.1 has an IC50 fold change of 0.30x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604,24130" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H,N856K" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigms’ ACE-2 variant LVE/STR chimera binds to SARS-2 Omicron variant B.1.1.529 spike protein trimer with high affinity. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.3 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "A67V,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.3 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22679,22679,22686,22992,21846,22992,22995,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075" "A67V,D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 4.2x-fold lower (95% CI: 0.15x-0.20x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22679,22679,22686,22992,21846,22992,22995,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075" "A67V,D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 6.2-fold lower (95% CI: 11.8x-14.3x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23048,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,24130,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22679,22679,22686,22992,21846,22992,22995,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075" "A67V,D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N856K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 28.7x-fold lower (95% CI: 0.03x-0.05) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23048,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,24130,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22679,22679,22686,22992,21846,22992,22995,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075" "A67V,D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N856K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 3.4-fold lower (95% CI: 3.2x-3.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23048,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,24130,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22679,22679,22686,22992,21846,22992,22995,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075" "A67V,D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N856K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "paired testing of vaccine sera against ancestral virus compared to Omicron BA.1 shows that 3-dose vaccine regimen provides over 50x fold increase in protection against Omicron(B.1.1.529 [BA.1]) compared to a 2-dose regimen." "" "" "" "Hao" "2022" "https://doi.org/10.1101/2022.08.12.22278720" "doi:10.1101/2022.08.12.22278720" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23048,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,24130,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22679,22679,22686,22992,21846,22992,22995,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075" "A67V,D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N856K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "4th antigenic exposure with Omicron (B.1.1.529 [BA.1])(n=29) infection increased variant specific plasma antibody and memory B cell responses as well as overall increased strain specific memory in individuals aged 22 –79 years, median age=33.5 years. Data collected 2.4 months after 3rd vaccination." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800" "D80N" "NC_045512.2:g.238G>A" "YP_009724390.1:p.Asp80Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800" "D80Y" "NC_045512.2:g.238G>T" "YP_009724390.1:p.Asp80Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This AA substitution outside the receptor binding domain in pseudotyped VSV promoted a 7.2% transduction rate in golden hamster cells, which was higher than that of human epithelial-like Huh-7 cells (6.6%)." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800,22188,22206,22597,22597,22599,23011,23012,23521,23521,23522,23524,23524,23525,23525,23604,23604" "D80Y,I210del,D215G,R346K,R346K,R346K,E484K,E484K,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Asp80Tyr,YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.VOI.V2 (first identified in Angola) reduced 8.0x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "One individual of 30 in the study, with HLA supertype HLA*A24:02, had a linear epitope that overlaps this variant of concern." "" "" "" "Redd" "2021" "https://doi.org/10.1101/2021.02.11.21251585" "doi:10.1101/2021.02.11.21251585" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolishes neutralizing activity of N-terminal-domain-directed mAb 4-19." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated that there is no free energy change (ddG) for this variant (i.e. same stability as wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In an Ontario long term care facility, cumulatively, weaker BNT162b2 vaccine stimulation, age/comorbidities, produced a ∼130-fold reduction in apparent neutralization titers in mean 88yo LTCH residents against Beta (B.1.351), relative to staff vaccinees against D614G wild type. 37.9% of 116 two-dose-mRNA-vaccinated residents had undetectable neutralizing antibodies to B.1.351. mRNA-1273 vaccinee sera displayed ~2 better neutralization than BNT162b2. [common defining B.1.351 mutations noted, as the manuscript does not provide details]" "" "" "" "Abe" "2021" "https://doi.org/10.1101/2021.08.06.21261721" "doi:10.1101/2021.08.06.21261721" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~10-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~3 fold without the deletion] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were significant, but ~500x weaker than in previously infected patients after first dose." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, 7 of 15 neutralized this B.1.351 pseudotype that includes the L242del, and only one had titers above 100. Only one of the 15 sera achieved 80% neutralization. [compare to 5 and 1 for pseudotype without the deletion]" "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.351 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 71%, Day 209 54%. Detectable antibodies against B.1.351 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 79%, Day 209 58%. Detectable antibodies against B.1.351 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 63%, Day 43 100%, Day 119 71%, Day 209 79%. Decreased neutralization on some assays was seen especially in those vaccinees tested that were 71+." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The B.1.351 variant constellation causes an ∼20-fold increase in affinity for ACE2 compared with Wuhan RBD, which may influence transmissibility." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Beta (B.1.351) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "humoral response durability" "" "" "In a prospective study of 107 hospitalized patients, decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7 and P.1 variants for at least 6 months (last of two samples taken) in patients previously hospitalized for COVID-19. A weaker protection was however observed for the B.1.351 variant." "" "" "" "Betton" "2020" "https://doi.org/10.1093/cid/ciab308" "doi:10.1093/cid/ciab308" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Beta (B.1.351) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Beta Molnupiravir (MK-4482) had ~1.75x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.351 defining mutations: Significant shift to infection in those without pre-existing conditions (79.6% vs 89% for non-VOC cases). Significant increase in hospitalization rate (19.3% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.3% vs 0.6% for non-VOC cases). PG: seems to be different notations around the LAL deletion, using the minimal shared definition to catch as many as possible." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Testing against B.1.351 the 20 most effective mAbs (19 anti-RBD, 1 anti-NTD) from a screen of 377 against wild type, 4 of 20 antibodies had >10-fold fall in neutralization titers, with most of these showing a complete knockout of activity. This is in line with the key roles of K417, E484, and N501, in particular E484, in antibody recognition of the ACE2 interaction surface of the RBD. Regeneron mAb cocktail: The neutralization of REGN10987 was unaffected by B.1.351, while REGN10933 was severely impaired (773-fold). AstraZeneca mAb cocktail: Neutralization by the AZ pair of antibodies was little affected on B.1.351 compared with Victoria." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v1 virus has reduced neutralization activity vs wild type: 34.5x (30 sera Pfizer median 9 days post 2nd dose) and 27.7x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination." "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination." "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Unlike wild type or B.1.1.7, B.1.351 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. PG: The virus used in these expriments has a non-typical deletion+sub in the 242 region." "" "" "" "Montagutelli" "2021" "https://doi.org/10.1101/2021.03.18.436013" "doi:10.1101/2021.03.18.436013" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Compared to Alpha (B.1.1.7) variant, odds of progressing to severe disease were 1.24-fold (95% CI: 1.11-1.39) higher for Beta. Odds of progressing to critical disease were 1.49-fold (95% CI: 1.13-1.97) higher. Odds of COVID-19 death were 1.57-fold (95% CI: 1.03-2.43) higher." "" "" "" "Abu-Raddad" "2021" "https://doi.org/10.1101/2021.08.02.21261465" "doi:10.1101/2021.08.02.21261465" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A two-dose regimen of (AstraZeneca) ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, vaccine efficacy against severe Covid-19 is undetermined." "" "" "" "Madhi" "2021" "https://doi.org/10.1101/2021.02.10.21251247" "doi:10.1101/2021.02.10.21251247" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine plasma neutralization of B.1.351-spike virus was nominally robust but lower (~3x) than other variants of concern." "" "" "" "Liu" "2021" "https://doi.org/10.1056/NEJMc2102017" "doi:10.1056/NEJMc2102017" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Beta (B.1.351) variant is 0.4x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Beta (B.1.351) has an IC50 fold change of 0.88x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Beta (B.1.351) has an IC50 fold change of 0.15x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v3 reduced 8.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x cleavage of S2 relative to WA1 (D614G) wildtype by Beta variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but A701V is downstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 34 convalescent cases 4–9 weeks following infection in June 2020, before the emergence of B.1.1.7, neutralization titers against B.1.351 were, on average, 13.3-fold reduced compared with an early Victoria sample (p < 0.0001). Significantly, 18 of 34 samples failed to reach 50% neutralization at a plasma dilution of 1:20, with a number showing a near total reduction of neutralization activity. In 13 convalescent cases 4–9 weeks following infection with B.1.1.7, neutralization titers against B.1.351 were, on average, 3.1-fold reduced compared with an early Victoria sample (p < 0.0001)." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using B.1.351 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~3-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~10 fold with L242del] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were signficiant, but >100x weaker than in previously infected patients after first dose." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, one third (5/15) of sera neutralized this B.1.351 pseudotype and only three had ID50 titers above 100. Only two of the 15 sera achieved 80% neutralization." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664,23399,23401,23401,23402,23403,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23664,23060,23061,23062,23062,23063,23063,23011,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Inoculation with the B.1.351 isolate resulted in lower clinical scores in 6 rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. Our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity." "" "" "" "Munster" "2021" "https://doi.org/10.1101/2021.05.07.443115" "doi:10.1101/2021.05.07.443115" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23664,23060,23061,23062,23062,23063,23063,23011,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission." "" "" "" "Yinda" "2021" "https://doi.org/10.1101/2021.05.05.442780" "doi:10.1101/2021.05.05.442780" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23664,23060,23061,23062,23062,23063,23063,23011,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission." "" "" "" "Yinda" "2021" "https://doi.org/10.1101/2021.05.05.442780" "doi:10.1101/2021.05.05.442780" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22810,22811,22812,22813,22813,22813,23664,23060,23061,23062,23062,23063,23063,23011,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "4 health care workers in the 20's and 30's with no underlying conditions and seropositivity or confirmed 2020 SARS-CoV-2 infections were confirmed to have B.1.351 infection during a Februrary 2021 hospital outbreak in Luxembourg. Symptoms were mostly mild on first infection, and milder on second infection." "" "" "" "Staub" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.18.2100423" "doi:10.2807/1560-7917.ES.2021.26.18.2100423" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.351 in 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "During an outbreak of SARS-CoV-2 501Y.V2 in a nursing home, all non-vaccinated residents (5/5) versus half of those fully vaccinated 2-5 weeks prior with BNT162b2 (13/26) were infected. Two of 13 vaccinated versus 4 of 5 non-vaccinated residents presented severe disease. BNT162b2 did not prevent the outbreak, but reduced transmission and disease severity. Among the 13 fully vaccinated residents who were infected, 2 (15.4%) presented with an asymptomatic disease, 9 (69.2%) developed mild to moderate symptoms, and 2 (15.4%) progressed to severe disease with fatal evolution secondary to acute respiratory distress syndrome (ARDS). There was no relationship between anti-S antibody levels at diagnosis and disease severity. Overall, the proportion of residents with severe disease in the non-vaccinated group (4/5) was higher than that in the vaccinated group (2/13). Only 1 vaccinated staff, but 10 unvaccinated were infected in the outbreak (no severe disease)." "" "" "" "Bailly" "2021" "https://doi.org/10.1093/cid/ciab446" "doi:10.1093/cid/ciab446" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.351 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0020 for moderate resistance." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer" "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer" "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.351 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. B.1.1.351 variant constellation ablates Class 3 N-terminal domain targeting antibodies COV2-2489 and COV2-2676 (the only two tested)." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In a Syrian hamster model, B.1.351 variant virus had >4x reduction in YRNT90 (measure of neutralization) using wild type convalescent sera. PG: Note that exact sequence for B.1.351 used was not disclosed." "" "" "" "Cochin" "2021" "https://doi.org/10.1101/2021.04.19.440435" "doi:10.1101/2021.04.19.440435" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.351 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the B.1.351 variants used, using the most popular as a stad in]" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v3 virus has reduced neutralization activity vs wild type: 42.4x (30 sera Pfizer median 9 days post 2nd dose) and 19.2x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype B.1.351 showed slight decrease in cell entry relative to wild type in 263T-ACE2 (kidney) cell line, and slight increase in Calu-3 (lung). Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.351 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "VSV pseudotype B.1.351 entry mediated by the S proteins of the B.1.351 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In one of eight cell lines tested (293T lung cells), a modest increase in cell entry was observed." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.351 lineage effectiveness was observed as 16.9% (95% CI [10.4,23.0]) against infection, and 0% against severe/critical/fatal disease (95% CI [0-19.0]). Two weeks or more after 2nd dose, effectiveness climbed to 75.0% [70.5,78.9] against infection, and 100% against severe/critical/fatal disease (95% CI [73.7,100])." "" "" "" "" "" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Approximately 6-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "VSV pseudotype B.1.351 showed 7.86-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections)." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abrogates Bamlanivimab, Etesevimab, or their combined use neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V" "" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine elicited antibodies neutralized virus with the B.1.351 spike protein had an average 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846" "T95I" "NC_045512.2:g.284C>T" "YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "65yo female with no severe Covid-19 risk factors tested positive 36 days after second dose of BNT162b2 (Pfizer) vaccine. Presented with fatigue, sinus congestion, and a headache developed; her symptoms plateaued and began to resolve six days later. [Mising genome coverage in regions of Spike covering clinically relevant mutations K417T, L452R, E484K, A701V, D796H, N501Y]" "" "" "" "Hacisuleyman" "2021" "https://doi.org/10.1056/NEJMoa2105000" "doi:10.1056/NEJMoa2105000" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22317,22319,22320,23399,23401,23401,23402,23403,23403" "T95I,D253G,D253G,D253G,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "B.1.526 (Iota) substantially increased IFR in older adults: by 46% (95% CI: 7.4 – 84%) among 45-64 year-olds, 82% (95% CI: 20 – 140%) among 65-74 year-olds, and 62% (95% CI: 45 – 80%) among 75+ during Nov 2020 – Apr 2021, compared to baseline IFR estimated for preexisting variants. [minimum clade defining mutations listed]" "" "" "" "Yang" "2021" "https://doi.org/10.1101/2021.08.04.21261596" "doi:10.1101/2021.08.04.21261596" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Sera from individuals who have been infected with Delta does not have strong neutralising activity against B.1.621" "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 69 test-positive were Mu. Two dose vaccine efficacy against Mu was 90.4% (73.9-96.5%), one dose VE was 45.8% (0.0-88.9%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from vaccinees [ChAdOx1 and BNT162b2 primarily used in UK] shows decreased ability to neutralize B.1.621 compared to first wave virus and Alpha, with a magnitude of change similar to Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against B.1.621." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D950N" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 12.4x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. [This is a greater reduction than Beta @ 8.2x]" "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D950N" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using live B.1.621 virus and a cytopathic effect-based assay, sera from 37 Pfizer/BioNTech BNT162b2 vaccinees collected 10-20 days post-booster showed significantly lower (95) but still ""robust"" neutralization than against ancestral B.1 virus (107)." "" "" "" "Messali" "2021" "https://doi.org/10.1002/jmv.27247" "doi:10.1002/jmv.27247" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24410" "T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D950N" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 7.6x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. [This is a greater reduction than Beta @ 6.3x]" "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22679,22679,23039,23039,23040,23521,23521,23522,23524,23524,23525,23525,24130,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,23060,23061,23062,23062,23063,23063,22879,22879,22881,22882,22882,22882,21618,23071,23071,23074,23074,23075,23075,22992,22995,23048,22810,22810,22811,22812,22813,22813,22813,22576,22577,22578,23604,23604,22686,23053,23053,23054,23054,23055,23055,22992,23009,23010,23012,23013,23399,23401,23401,23402,23403,23403" "T95I,S373P,S373P,Q493R,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,P681H,S375F,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 1.5x-fold lower (95% CI: 0.05x-0.07x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22679,22679,23039,23039,23040,23521,23521,23522,23524,23524,23525,23525,24130,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,23060,23061,23062,23062,23063,23063,22879,22879,22881,22882,22882,22882,21618,23071,23071,23074,23074,23075,23075,22992,22995,23048,22810,22810,22811,22812,22813,22813,22813,22576,22577,22578,23604,23604,22686,23053,23053,23054,23054,23055,23055,22992,23009,23010,23012,23013,23399,23401,23401,23402,23403,23403" "T95I,S373P,S373P,Q493R,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,P681H,S375F,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 4.4-fold lower (95% CI: 4.3x-4.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,23011,23012,23271,23399,23401,23401,23402,23403,23403,23604,23604,23948" "T95I,E484K,E484K,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D796H" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp796His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "51yo female with no severe COVID-19 risk factors tested positive 19 days after second dose of mRNA-1273 (Moderna) vaccine. Presented with sore throat, congestion, and headache developed; the next day she lost her sense of smell. Symptoms resolved over a one week period. Serum obtained 4 days after symptom onset was tested for neutralization against wild-type virus, the E484K mutant, and the B.1.526 variant. It was equally effective against each. These data suggest that the antibody response recognized these variants but was nonetheless insufficient to prevent a breakthrough infection. The virus detected matched neither B.1.1.7 nor B.1.526 VOC strains in wide circulation in New York at the time of infection, though shared some mutations." "" "" "" "Hacisuleyman" "2021" "https://doi.org/10.1056/NEJMoa2105000" "doi:10.1056/NEJMoa2105000" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,23399,23401,23401,23402,23403,23403" "T95I,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21855" "S98F" "NC_045512.2:g.293C>T" "YP_009724390.1:p.Ser98Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly enhanced the transduction rate in raccoon dog (Nyctereutes procyonoides) kidney (62.4%) and Rickett’s big-footed bat (Myotis pilosus) kidney (45.0%) cell cultures compared to epithelial-like human Huh-7 cells (38.9%)." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21929" "A123S" "NC_045512.2:g.367G>T" "YP_009724390.1:p.Ala123Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected in passage with mAb COV2-2489 during alanine mutagenesis antibody mapping experiment." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21969" "C136Y" "NC_045512.2:g.407G>A" "YP_009724390.1:p.Cys136Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massively decreases N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21969" "C136Y" "NC_045512.2:g.407G>A" "YP_009724390.1:p.Cys136Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected twice in passage with mAb COV2-2489." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. [PG: This mutation is adjacent to a well known deletion, which may confound the significance of this variant]" "" "" "" "Lucaci" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "These variants dominate in mink infections in North America, sometime supplemented with F486L. The Y453F variant found in other jurisdictions in mink infections is notably absent in North America." "" "" "" "" "2021" "https://doi.org/10.1101/2021.03.18.21253734v3" "doi:10.1101/2021.03.18.21253734v3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~3.5x cleavage of S2 relative to WA1 (D614G) wildtype by Kappa (B.1.617.1) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~4.5x for closely related Delta B.1.617.2 also with P681R at the cleavage site)." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Kappa (B.1.617.1) shows mean 1.97x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617.1) showed a 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.1) showed a 1.12x increase in binding (KD) relative to D614G, but described as ""not significant"". [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617.1) showed a 1.79x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Average 2x neutralization efficiency decrease against sera from 26 Phase II trial Covaxin (BBV152) vaccine recipents. Very similar to B.1.1.7 (~2x) in the same study, and the neutralization from 17 sera of natural infections across B1 lineages." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.04.23.441101" "doi:10.1101/2021.04.23.441101" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cluster of B.1.617[.1] infections related to travel from India to USA, one patient with mild symptoms had received their second dose of Pfizer vaccine more than two weeks before the infection [i.e. vaccine breakthrough]." "" "" "" "Verghese" "2021" "https://doi.org/10.1128/JCM.00741-21" "doi:10.1128/JCM.00741-21" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Kappa (B.1.617.1) shows 5.71x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H,T95I" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Kappa (B.1.617.1) has an IC50 fold change of 0.68x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H,T95I" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Kappa (B.1.617.1) has an IC50 fold change of 2.3x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H,T95I" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Kappa (B.1.617.1) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,Q1071H,T95I" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Kappa (B.1.617.1) has an IC50 fold change of 80.2x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Omicron BA.2 variant is 0.8x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Omicron BA.2 has an IC50 fold change of 0.08x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.2 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Omicron BA.2 has an IC50 fold change of 0.09x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.2 has an IC50 fold change of 0.04x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.2 has an IC50 fold change of 0.07x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23604,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H" "" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.2 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21974" "D138Y" "NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.43 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21977" "P139S" "NC_045512.2:g.415C>T" "YP_009724390.1:p.Pro139Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected once in passage with mAb COV2-2676." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990" "Y145del,Y145del" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient." "" "" "" "McCarthy" "2021" "https://doi.org/10.1126/science.abf6950" "doi:10.1126/science.abf6950" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990" "Y145del,Y145del" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990,21993,21995,23011,23012,23399,23401,23401,23402,23403,23403" "Y145del,Y145del,H146del,H146del,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.His146del,YP_009724390.1:p.His146del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Normalized for particle number, on ACE2.293T cells showed that the B.1.618 spike protein was about as infective as D614G wild type." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21993,21995" "H146del,H146del" "NC_045512.2:g.436_438del,NC_045512.2:g.436_438del" "YP_009724390.1:p.His146del,YP_009724390.1:p.His146del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient." "" "" "" "McCarthy" "2021" "https://doi.org/10.1126/science.abf6950" "doi:10.1126/science.abf6950" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21997,21997,21998,21999,22000,22000,22001" "K147E,K147E,K147E,K147E,K147E,K147E,K147E" "" "YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21997,21997,21998,21999,22000,22000,22001" "K147E,K147E,K147E,K147E,K147E,K147E,K147E" "" "YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21998,21998" "H146Y,H146Y" "NC_045512.2:g.436C>T," "YP_009724390.1:p.His146Tyr,YP_009724390.1:p.His146Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in 4A8 monoclonal antibody EC50 (i.e. ablated recognition), but much milder effect on mAbs within antigenic supersite ""i""" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22001" "K147Q" "NC_045512.2:g.439A>C" "YP_009724390.1:p.Lys147Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22002" "K147T" "NC_045512.2:g.440A>C" "YP_009724390.1:p.Lys147Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22002" "K147T" "NC_045512.2:g.440A>C" "YP_009724390.1:p.Lys147Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massively decreases N terminal domain antigen recognition by supersite i mAbs S2M28, S2X28, S2X333, 4A8 (but not S2L28)." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22003" "K147N" "NC_045512.2:g.441A>T" "YP_009724390.1:p.Lys147Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22005" "N148S" "NC_045512.2:g.443A>G" "YP_009724390.1:p.Asn148Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong positive selection (up to 72% of supernatant sequences) under six rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22010" "K150E" "NC_045512.2:g.448A>G" "YP_009724390.1:p.Lys150Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong positive selection (up to 40% of supernatant sequences) under three rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22010" "K150E" "NC_045512.2:g.448A>G" "YP_009724390.1:p.Lys150Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22011" "K150R" "NC_045512.2:g.449A>G" "YP_009724390.1:p.Lys150Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 18% of supernatant sequences) under two rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22011" "K150T" "NC_045512.2:g.449A>C" "YP_009724390.1:p.Lys150Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 22% of supernatant sequences) after COV47 convalescent plasma assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22016,22016,22016" "W152R,W152R,W152R" ",NC_045512.2:g.454T>A,NC_045512.2:g.454T>C" "YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For NTD-binding neutralizing antibody ADI-56479 this mutation causes a 1000x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22016,22016,22016" "W152R,W152R,W152R" ",NC_045512.2:g.454T>A,NC_045512.2:g.454T>C" "YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22018" "W152C" "NC_045512.2:g.456G>T" "YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Pseudoviruses carrying the W152C mutation demonstrated small increases in cell entry compared to D614G alone in 293T cells and human airway organoids." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22018" "W152C" "NC_045512.2:g.456G>T" "YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The W152C mutation reduced recognition of six NTD neutralizing mAbs, including a complete loss of binding for two of them, with a complementary pattern to that observed for S13I (also found in lineage B.1.427/B.1.429) out of 11 neutralizing mAbs evaluated." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022" "E154K" "NC_045512.2:g.460G>A" "YP_009724390.1:p.Glu154Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604" "E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abrogates Bamlanivimab neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Significant decrease in combined Etesevimab+Bamlanivimab neutralization except at the highest concentration measured. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604" "E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pfizer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~3x (compared to ~11x for B.1.351). [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604" "E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Approximately 2-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23604,23604" "E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R" "" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In two of eight cell lines tested (Caco-2 intenstinal and Calu-3 lung), a modest increase in cell entry was observed. This increase was not observed in a Calu-3 cell line with overexpressed ACE2. [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22028,22034" "R158G,R158G" "NC_045512.2:g.467_472del,NC_045512.2:g.472A>G" "YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22033,23011,23012,23604,23604" "F157L,E484K,E484K,P681R,P681R" "" "YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.23.1-v2 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22033,23604,23604" "F157L,P681R,P681R" "NC_045512.2:g.471C>A,NC_045512.2:g.2042C>G," "YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.23.1-v1 reduced 1.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22036" "R158S" "NC_045512.2:g.474A>T" "YP_009724390.1:p.Arg158Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected three times in passage with mAb COV2-2489." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:03." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DPB1*04:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*07:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type C*07:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*16:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22107,22111" "Q183H,Q183H" "NC_045512.2:g.549G>T,NC_045512.2:g.549G>T" "YP_009724390.1:p.Gln183His,YP_009724390.1:p.Gln183His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome" "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132" "R190S" "NC_045512.2:g.570G>T" "YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.69 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132,22600,22600,22907,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in B.1.640.2 variant was ~1000x folds more significant in 8 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132,22600,22600,22907,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604" "R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1.640.2 variant was ~5.6x folds more significant in 9 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22188,23399,23401,23401,23402,23403,23403" "I210del,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "A 42yo Iranian male was reinfected with B.1.36 lineage virus 128 days after infection with genetically distinct B.1.36 virus, with negative PCR tests in between. In the first instance patient presented with cough, headache, severe diarrhea. In the second instance symptoms were more severe: body pain, shortness of breath, headache and anosmia. Anti-SARS-CoV-2 IgG and IgM tests were negative after both episodes. [Non-seroconversion may be associated with elevated risk of re-infection] [I210del is a homoplasy that has appeared in several disparate parts of the global phylogenetic tree, including A and B lineages, primarily in LMICs]" "" "" "" "Salehi-Vaziri" "2021" "https://doi.org/10.1016/j.virusres.2021.198421" "doi:10.1016/j.virusres.2021.198421" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:02." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.98 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:01." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*13:02." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227" "A222V,A222V" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227,23399,23401,23401,23402,23403,23403" "A222V,A222V,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3). Both cases were mild. Second case also includes N:p.A220V" "" "" "" "Brehm" "2021" "https://doi.org/10.3390/v13040661" "doi:10.3390/v13040661" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227,23399,23401,23401,23402,23403,23403" "A222V,A222V,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "humoral response durability" "" "" "27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3), i.e. with a 9 month interval. Both cases were mild. No significant differences in the neutralizing capacity of the two lineages were observed in 4 sera taken (1 pre-reinfection, three post-reinfection). Neutralizing antibody titres (IC50) before and immediately after re-infection were <300 against both strains, and jumped >7x upon re-infection. Viral titres were also higher in the second case. Second case also includes N:p.A220V" "" "" "" "Brehm" "2021" "https://doi.org/10.3390/v13040661" "doi:10.3390/v13040661" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22293" "L244S" "NC_045512.2:g.731T>C" "YP_009724390.1:p.Leu244Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22301" "S247R" "NC_045512.2:g.739A>C" "YP_009724390.1:p.Ser247Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22304" "Y248H" "NC_045512.2:g.742T>C" "YP_009724390.1:p.Tyr248His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22314" "P251L" "NC_045512.2:g.752C>T" "YP_009724390.1:p.Pro251Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317" "G252D" "NC_045512.2:g.755G>A" "YP_009724390.1:p.Gly252Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317,22319,22320" "D253G,D253G,D253G" "NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317,22319,22320" "D253G,D253G,D253G" "NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22319" "D253Y" "NC_045512.2:g.757G>T" "YP_009724390.1:p.Asp253Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22323" "S254F" "NC_045512.2:g.761C>T" "YP_009724390.1:p.Ser254Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22323" "S254Y" "NC_045512.2:g.761C>A" "YP_009724390.1:p.Ser254Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22326" "S255F" "NC_045512.2:g.764C>T" "YP_009724390.1:p.Ser255Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22328,22329,22331" "G257S,G257S,G257S" "NC_045512.2:g.769G>A,NC_045512.2:g.769G>A,NC_045512.2:g.769G>A" "YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334" "W258R" "NC_045512.2:g.772T>C" "YP_009724390.1:p.Trp258Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334" "W258R" "NC_045512.2:g.772T>C" "YP_009724390.1:p.Trp258Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334,22879,22879,22881,22882,22882,22882,22904,22910,23011,23012" "W258R,N440K,N440K,N440K,N440K,N440K,N440K,N450D,N450D,E484K,E484K" "" "YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22340" "A260T" "NC_045512.2:g.778G>A" "YP_009724390.1:p.Ala260Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22344" "G261D" "NC_045512.2:g.782G>A" "YP_009724390.1:p.Gly261Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Multiple mink but no humans on one farm in Denmark, potential adaptation." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22377,22377" "P272L,P272L" ",NC_045512.2:g.815C>T" "YP_009724390.1:p.Pro272Leu,YP_009724390.1:p.Pro272Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*08:01." "" "" "" "Dolton" "2021" "https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf" "doi:10.1101/2021.06.21.21259010v2.full.pdf" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22377,22377" "P272L,P272L" ",NC_045512.2:g.815C>T" "YP_009724390.1:p.Pro272Leu,YP_009724390.1:p.Pro272Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*02:01." "" "" "" "Dolton" "2021" "https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf" "doi:10.1101/2021.06.21.21259010v2.full.pdf" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22573,22574,22576,22577" "G339H,G339H,G339H,G339H" "" "YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22573,22574,22576,22577,22595,22596,22597,22597,22599,22599,22679,22679,22686,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22895,22939,22939,22942,22942,22942,22992,23009,23010,23012,23013,23017,23018,23027,23029,23029,23030,23031,23031,23053,23053,23054,23054,23055,23055,22992,22995,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075" "G339H,G339H,G339H,G339H,R346T,R346T,R346T,R346T,R346T,R346T,S373P,S373P,S375F,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,V445P,N460K,N460K,N460K,N460K,N460K,S477N,E484A,E484A,E484A,E484A,F486P,F486P,F490S,F490S,F490S,F490S,F490S,F490S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,T478K,T478K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Val445Pro,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The hACE2-binding affinity of XBB.1.5 RBD has a dissociation constant KD of 3.4 nM, where S486P is the distinguishing Spike mutation vs parent XBB.1 RBD with a much weaker KD (19 nM), as measured by surface plasmon resonance (SPR) assays." "" "" "" "Yue" "2023" "https://doi.org/10.1101/2023.01.03.522427" "doi:10.1101/2023.01.03.522427" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 1.2x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.3 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22577" "G339N" "" "YP_009724390.1:p.Gly339Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.11 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22583" "V341I" "NC_045512.2:g.1021G>A" "YP_009724390.1:p.Val341Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22597,22599,22599" "R346T,R346T,R346T,R346T,R346T,R346T" "" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22597,22599,22599" "R346T,R346T,R346T,R346T,R346T,R346T" "" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22597,22599" "R346K,R346K,R346K" ",NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22597,22599" "R346K,R346K,R346K" ",NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 53% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22597,22599" "R346K,R346K,R346K" ",NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation, which has emerged in some Omicron sequences, has a 0.7x reduction in neutralization activity with Sotrovimab in a VSV model on Vero E6 cells. [Omicron sequences with R346K may very well have a non-additive neutralization rather than 2.7x+0.7x = 3.4x]" "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346I,R346I" "NC_045512.2:g.1037G>T,NC_045512.2:g.1037G>T" "YP_009724390.1:p.Arg346Ile,YP_009724390.1:p.Arg346Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Provides ~80% escape from mAb COV2-2130, even though its appearance in culture is formed without selective mAb pressure." "" "" "" "Dong" "2021" "https://doi.org/10.1101/2021.01.27.428529" "doi:10.1101/2021.01.27.428529" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22598" "R346E" "" "YP_009724390.1:p.Arg346Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.08 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 2/3 antibody C603." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 30% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 2/3 antibody C603." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22622" "N354D" "NC_045512.2:g.1060A>G" "YP_009724390.1:p.Asn354Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.13 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22623" "N354S" "" "YP_009724390.1:p.Asn354Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.17 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22624" "N354K" "NC_045512.2:g.1062C>A" "YP_009724390.1:p.Asn354Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22627,22627,22629" "K356T,K356T,K356T" ",NC_045512.2:g.1067A>C,NC_045512.2:g.1067A>C" "YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.14 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22629" "K356R" "NC_045512.2:g.1067A>G" "YP_009724390.1:p.Lys356Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22632" "R357K" "NC_045512.2:g.1070G>A" "YP_009724390.1:p.Arg357Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.18 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.72 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as ""stabilizing"" since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as ""stabilizing"" since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22661" "V367I" "NC_045512.2:g.1099G>A" "YP_009724390.1:p.Val367Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22679,22679" "S373P,S373P" "NC_045512.2:g.1117T>C," "YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Reduce affinity for mildly cross-reactive CR3022 (2003 pandemic SARS monoclonal antibody cross-reactive to SARS-CoV-2)" "" "" "" "Long" "2020" "https://doi.org/10.1128/mBio.02707-20" "doi:10.1128/mBio.02707-20" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22679,22679,23009,23010,23012,23013" "S373P,S373P,E484A,E484A,E484A,E484A" "" "YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "On December 7, 2021 the estimate of Omicron effective reproduction rate (Rt) is 3.12 [presumably R0 is higher], compared to 1.12 for the dominant Delta VOC at that time. [shorthand of variant list shraed by all contemporary BA lineage used here]" "" "" "" "" "2021" "https://doi.org/10.47326/ocsat.dashboard.2021.1.0" "doi:10.47326/ocsat.dashboard.2021.1.0" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22686" "S375F" "NC_045512.2:g.1124C>T" "YP_009724390.1:p.Ser375Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch." "" "" "" "Lucaci" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22696" "K378N" "NC_045512.2:g.1134G>T" "YP_009724390.1:p.Lys378Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for mildly neutralizing COV2-2677 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23401,23402,23403,23403" "P384L,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23401,23402,23403,23403" "P384L,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23401,23402,23403,23403" "P384L,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22745" "V395I" "NC_045512.2:g.1183G>A" "YP_009724390.1:p.Val395Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22766" "I402V" "NC_045512.2:g.1204A>G" "YP_009724390.1:p.Ile402Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22783,22783,22784,22785,22786,22786" "R408S,R408S,R408S,R408S,R408S,R408S" ",NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C" "YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22783,22783,22784,22785,22786,22786,23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "R408S,R408S,R408S,R408S,R408S,R408S,E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a study of 481 vaccinees going from lowest to highest infection rate, 2 doses of CoronaVac and 1 dose of BNT162b2 had the lowest infection rate at 6.3%, then it was 3 doses of BNT162b2 having a infection rate of 16.6%. 2 and 3 doses of CoronaVac had 48.6% and 20.6% infection rate respectively. 2 doses of BNT162b2 has the highest infection rate at 49.2%." "" "" "" "Zhou" "2022" "https://doi.org/10.1101/2022.05.09.491254" "doi:10.1101/2022.05.09.491254" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22784" "R408G" "" "YP_009724390.1:p.Arg408Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.09 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection, Two-tailed Wilcoxon matched-pairs signed-rank test shows mild resistance P=0.0361." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C682, and to a lesser extent C614 and C660" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs)" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs)" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates binding by RBD-directed mAbs CB6 and 910-30 (targeting the inner side of the RBD). Pseudotyped virus model impairs binding by RBD-directed mAbs 4-20 and REGN10933." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~6x binding against this isolated mutation. Estesevimab lost ~100x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 7.5 fold decrease in KD value for antibody binding of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 36.9 fold decrease in KD value for antibody binding of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "1.1 fold drop in IC50 of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 1.5 fold decrease in KD value of antibody binding of ACE2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The K417N mutation decreased the affinity ~4 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 3-fold decrease in affinity compared to wild-type RBD on the cell surface (Kd = 145.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.86 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813" "K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against IgG1 monoclonal antibody ab1." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Moderna vaccinee sera, 2.7x reduction in neutralization, and 6.4 for the full B.1.351 Spike mutation complement, but despite the observed decreases, titers in human vaccinee sera against the B.1.351 variant remained at clinically significant level of ~1/300." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.01.25.427948" "doi:10.1101/2021.01.25.427948" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.351 and P.1 samples showed average Ct cycle threshold of 22.2 vs 23 for wildtype (i.e. ~60% higher viral load) comparing 3360 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26)." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "27% of 44 early pandemic exposure convalescent plasma/sera lose all activity against a RBD triple mutant pseudovirus (RBD mutatants of the 501Y.V2 ""South African"" lineage), while only 23% retained high titres" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from B.1.351." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26)." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibodies ab8 and IgG1 ab1. Complete loss for the same antibodies was also observed against S1 pseudotyped and full Spike protein trimers with both B.1.351 and P.1 lineage variants, with slight binding signal for P.1 against IgG1 at the highest concentration tested (1uM). Complete loss of neutralization by these two antibodies was also observed." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of the B.1.351 RBD variants for ACE2 increased by 3.7 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.4-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.351 key variants lentivirus. Compare to 8.8-fold reduction against cultured B.1.351 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This combination showed ~3x increase binding to ACE2 vs wild type, about half that of the B.1.1.7 lineage, suggesting that the K417N mutation is slightly detrimental to ACE2 binding, probably as a result of disrupting the salt bridge formed with ACE2 residue D30" "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant of key B.1.351 lineage mutations showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolished neutralization by mAbs CQ026 and CQ038, greatly diminished neutralization by CQ012 and CQ046." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) with enrollment June 24 and November 9, 2020 from ~2000 HIV-negative 18-64 year olds (1:1 placebo to treatment), incidence of serious adverse events 14 or more days post- 2nd dose was balanced between the vaccine and placebo groups. A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed 3.5x reduction in neutralization (ID50) for B.1.351 RBD pseudotype HIB-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a similar 3.2x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "36,590 variant-specific RT-PCR tests were performed on samples collected between April 12 and May 7, 2021 in France to compare variant spread. Compared to January to March 2021, B.1.351 variant had a significant transmission advantage over B.1.1.7 in some regions (15.1 to 16.1% in Île-de-France and 16.1 to 18.8% in Hauts-de-France). This shift in transmission advantage is consistent with the immune evasion abilities of B.1.351 and the high levels of immunization in these regions." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.05.12.21257130" "doi:10.1101/2021.05.12.21257130" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure." "" "" "" "Pearson" "2021" "https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure." "" "" "" "Pearson" "2021" "https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Average ~10-fold reduction in neutralization efficacy in convalescent sera of 16 health workers infected in Spring 2020." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 2 (B.1.351) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23011,23012,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23041,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Lung viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~2266x fold drop in the R3P1-E4 antibody in comparison to the IgG control." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23041,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "100% of the 5 8‑month‑old male R3P1-E4 antibody treated mice suvived 14 days after infection while only 60% the control group mice survived 5 days post infection." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23041,23060,23061,23062,23062,23063,23063" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trachea viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~750x fold drop in the R3P1-E4 antibody in comparison to the IgG control." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (no synergy as level approx. that of N501Y alone)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~5x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied]" "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22810,22811,22812,22813,22813,22813,23399,23401,23401,23402,23403,23403" "K417N,K417N,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22811" "K417H" "" "YP_009724390.1:p.Lys417His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22811" "K417D" "" "YP_009724390.1:p.Lys417Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Most and moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Mildly effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22811" "K417D" "" "YP_009724390.1:p.Lys417Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Most and moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Mildly effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22811" "K417H" "" "YP_009724390.1:p.Lys417His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22811" "K417D" "" "YP_009724390.1:p.Lys417Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, but moderate decrease in ACE2 binding affinity" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417I" "" "YP_009724390.1:p.Lys417Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417I" "" "YP_009724390.1:p.Lys417Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.39 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 antibody C682" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 57.1 fold decrease in KD value for antibody binding of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 1.1 fold decrease in KD value of antibody binding of ACE2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.25 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~16x binding against this isolated mutation. Estesevimab lost ~16x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "2.6 fold increase in IC50 of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 2.9 fold decrease in KD value for antibody binding of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The K417T mutation decreased the affinity ~2 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812" "K417T,K417T" "NC_045512.2:g.1250A>C," "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.64 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812,23011,23012,23060,23061,23062,23062,23063,23063" "K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of the P.1 RBD variants for ACE2 increased by 5.3 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812,23011,23012,23060,23061,23062,23062,23063,23063" "K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from P.1." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The KD for the pseudotyped P.1-ACE2 interaction is 4.8 nM, showing that binding to P.1 is essentially indistinguishable from B.1.351 (4.0 nM), which binds with ~19x greater affinity that wild type." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22851" "T430I" "NC_045512.2:g.1289C>T" "YP_009724390.1:p.Thr430Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22865" "A435S" "NC_045512.2:g.1303G>T" "YP_009724390.1:p.Ala435Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb H014 (on D614G background)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The N440K variant produced ten times higher infectious viral titers than a prevalent A2a strain, and over 1000 folds higher titers than a much less prevalent A3i strain prototype in Caco2 cells. Interestingly, A3i strain showed the highest viral RNA levels, but the lowest infectious titers in the culture supernatants, indicating the absence of correlation between the RNA content and the infectivity of the sample." "" "" "" "Tandel" "2021" "https://doi.org/10.1101/2021.04.30.441434" "doi:10.1101/2021.04.30.441434" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 0.7x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 3 antibody C669 mildly selected for the emergence of the N440K mutation in vitro (in contrast to N440H which caused mild escape in Class 1/2 mAb C653)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "N501Y substitution decreased the neutralizing and binding activities of CB6 and increased that of BD-23" "" "" "" "Cheng" "2021" "https://doi.org/10.1186/s12985-021-01554-8" "doi:10.1186/s12985-021-01554-8" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 45% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, eliminated in subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882" "N440K,N440K,N440K,N440K,N440K,N440K" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22879,22881,22882,22882,22882,23399,23401,23401,23402,23403,23403" "N440K,N440K,N440K,N440K,N440K,N440K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "A 47yo Indian male was reinfected with B.1.36 lineage virus in September 2020 after infection with genetically distinct B.1.36 virus in July, with negative PCR tests in between. While the forst episode was asymptomatic, the second included fever, cough, and malaise. The second case additionally contained stopgain ORF3a:E261*" "" "" "" "Rani" "2021" "https://doi.org/10.1002/jmv.26997" "doi:10.1002/jmv.26997" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444R" "NC_045512.2:g.1331A>G" "YP_009724390.1:p.Lys444Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Identified in 6/20 replicates of recombinant VSV growth in the presence of mAb COV2-2130." "" "" "" "Dong" "2021" "https://doi.org/10.1101/2021.01.27.428529" "doi:10.1101/2021.01.27.428529" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444R" "NC_045512.2:g.1331A>G" "YP_009724390.1:p.Lys444Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 20% of supernatant sequences) under two rounds of COV-NY convalescent plasma passage, eliminated in rounds three and four" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893,22893" "K444T,K444T" ",NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr,YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893,22893" "K444T,K444T" ",NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr,YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Results in 3.7-fold drop in neutralization potency for COVA2-29, which is a cluster I RBD141 specific antibody." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893,22893" "K444T,K444T" ",NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr,YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Improvement in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolishes binding efficiency vs wild type for mAb REGN10933." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-01 and moderately resistant to 2H04 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 14% of supernatant sequences) after COV-NY convalescent plasma assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22895" "V445P" "" "YP_009724390.1:p.Val445Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.05 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22896" "V445A" "NC_045512.2:g.1334T>C" "YP_009724390.1:p.Val445Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 41% appearance in 2 passages against Regeneron monoclonal antibody RGN10987 @ 10ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed a ~4x drop in sensitivity." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 1 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-02, SARS2-32 and SARS2-35 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Decrease in neutralization capability of all 4 convalescent sera tested (1 ablated)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2499 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations), triple replicates. Against a broader panel of 16 convalescent plasma (no replicates), reductions in neutralization are considerably less dramatic in pattern, and sometime neutralization increases." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 4 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 95% appearance in 2 passages against Regeneron monoclonal antibody RGN10934 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-07 nd moderately resistant to SARS2-16 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Most effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910,23011,23012,23039,23039,23040,23373,25045,25046,25046" "N450D,N450D,E484K,E484K,Q493R,Q493R,Q493R,T604I,P1162S,P1162S,P1162S" "" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Thr604Ile,YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22905" "N448S" "NC_045512.2:g.1343A>G" "YP_009724390.1:p.Asn448Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22907" "Y449H" "NC_045512.2:g.1345T>C" "YP_009724390.1:p.Tyr449His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22907" "Y449N" "NC_045512.2:g.1345T>A" "YP_009724390.1:p.Tyr449Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912,22912,22916" "L452M,L452M,L452M" ",NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A" "YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912,22912,22916" "L452M,L452M,L452M" ",NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A" "YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We observed increased entry by pseudoviruses carrying the L452R mutation compared to D614G alone, with a 6.7 to 22.5-fold increase in 293T cells and a 5.8 to 14.7-fold increase in human airway organoids." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 3 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Increased stability of RBD expression in yeast, suggesting increased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-02 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.32 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~5x binding against this isolated mutation. Cligavimab lost ~4x binding against this isolated mutation. Regdanvimab lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs X593 and P2B-2F6" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02." "" "" "" "Motozono" "2021" "https://doi.org/10.1016/j.chom.2021.06.006" "doi:10.1016/j.chom.2021.06.006" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Ablation of neutralization capability of 3 of 4 convalescent sera tested, the other is significantly hindered." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "L452R derivative virus did not induce IFN-gamma expression even at the highest concentration tested (10 nM) in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456)." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~1.7-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2/3 antibody C628 and class 2 antibody C643 selected for the emergence of the L452R mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Observed ~2x decrease on average in neutralization efficacy in convalescent sera of 16 health workers." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.67 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "10 of 14 RBD-specific mAbs that showed at least 10-fold reduced neutralization of B.1.427/B.1.429 variant pseudotype (S13I, W152C, and L452R) were also found to poorly bind to just a L452R RBD mutant, demonstrating a role for this mutation as an escape mechanism for certain RBD-targeting mAbs." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. L452R conferred about a two-fold reduction in neutralisation by vaccine sera, but was not statistically significant with this sample size." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. [listed as L454R in Figure, but L452R in text, also text suggests not statistically significant, but error bars say otherwise in Figure 4]" "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917" "L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23011,23012" "L452R,L452R,L452R,L452R,L452R,L452R,E484K,E484K" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant combination shows a ~4-5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, same as L452R alone." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23011,23012,23604,23604" "L452R,L452R,L452R,L452R,L452R,L452R,E484K,E484K,P681R,P681R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant combination shows a ~3x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, significantly less of a decrease than any B.1.617 lineage variants alone, suggesting a synergistic effect on cell entry while maintaining known immunity esacpe mutants." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484Q had a ~5x drop in neutralization (vs ~10x for E484K). When E484Q and L452R were combined, the fold change was significant, but similar to that of L452R alone (~2x), suggesting no evidence for an additive effect [perhaps even E484Q effect dilution]." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x infectivity advantage to the spike particles [less than L452R or E484Q alone working with the delins]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Pseudotyped viruses for B.1.617 was 2.3-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. [details on the convalescent patient sera collection are not abundantly clear in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2.5x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x drop in neutralization (NT50) [working with the delins, less than just L452R but more than just E484Q]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617) showed a 1.30x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.18x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The combination caused a 3-fold increase in infectivity relative to D614G wild type. [compare to 3.5x for L452R alone]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617) showed a 1.85x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617) showed a 1.22x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23604,23604" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,P681R,P681R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In 9 infected hamsters each for B.1 and B.1.617.1, no significant change in viral load or subgenomic RNA levels were detected." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.05.05.442760" "doi:10.1101/2021.05.05.442760" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23604,23604" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,P681R,P681R" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Gross examination of 3+3 hamster lung specimens showed pronounced congestion and hemorrhages on days 5 and 7 post-infection in the case of the B.1.617.1 as compared with the B.1. The lung lesions with the B.1 variant were minimal to mild whereas with B.1.617.1 they were moderate. For B.1 pneumonic changes were minimal to mild (inflammatory cell infiltration, focal consolidation and mild congestion). The pronounced changes (moderate to severe) with mononuclear infiltration in the alveolar interstitial space, interstitial septal thickening, consolidation and pneumocyte hyperplasia were observed with B.1.617.1 variant consistently." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.05.05.442760" "doi:10.1101/2021.05.05.442760" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23012,23604,23604,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,E484Q,P681R,P681R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Normalized for particle number, on ACE2.293T cells showed that the B.1.617 spike protein was >2-fold increase in infectivity relative to D614G wild type." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23060,23061,23062,23062,23063,23063" "L452R,L452R,L452R,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of these B.1.417/B.1.429 defining variants in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The L452R mutation increased the infectivity more than two-fold in these conditions." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this RBD mutation conferred a 2.36x drop in neutralization (NT50)." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~2x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 583 test-positive were Epsilon. Two dose vaccine efficacy against Epsilon was 97.6 (90.2-99.4%), one dose VE was 76.3 (48.1-89.1%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 7.42x drop in neutralization (NT50) [mostly from 3 of the sera]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403" "L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916" "L452W,L452W" "" "YP_009724390.1:p.Leu452Trp,YP_009724390.1:p.Leu452Trp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917" "L452Q" "NC_045512.2:g.1355T>A" "YP_009724390.1:p.Leu452Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917" "L452Q" "NC_045512.2:g.1355T>A" "YP_009724390.1:p.Leu452Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.27 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403" "L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.048x fold change in IC50 in C.37 Lambda" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403" "L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.038x fold change in IC50 in C.37 Lambda" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403" "L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 3.4x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403" "L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 1.7x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.25 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Casirivimab lost >50x binding against this mutation." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.celrep.2021.109017" "doi:10.1016/j.celrep.2021.109017" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "" "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed in 4 separate mink farms in Denmark, and Y453F is circulating relatively widely in humans." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02." "" "" "" "Motozono" "2021" "https://doi.org/10.1016/j.chom.2021.06.006" "doi:10.1016/j.chom.2021.06.006" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "VSV pseudotyped with Y453F reduced inhibition by most of the 13 potent convalescent serum/plasma samples tested, albeit with variable efficiency (median increase of serum/plasma titer required for 50% neutralization [NT50] = 1.62x, range = 1.02x to 3.43x), indicating that this RBD mutation may compromise SARS-CoV-2 control by preexisting neutralizing antibody responses." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.celrep.2021.109017" "doi:10.1016/j.celrep.2021.109017" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~12x binding against this double mutation. Casirivimab lost ~64x binding against this double mutation. Cligavimab lost ~6x binding against this double mutation. Estesevimab lost ~10x binding against this double mutation. Imdevimab lost ~5x binding against this double mutation. Regdanvimab lost ~8x binding against this double mutation. Sotrovimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "10-fold reduction in binding efficiency vs wild type for MAb REGN10933." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "The induction level of IFN-gamma expression by the Y453F derivative in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456) was significantly lower." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "Y453F,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "The so-called ""delta F"" variant combination previously observed in mink spillover events also emerged in a lymphoma patient (non-Hodgkin diffuse B-cell lymphoma IV stage B) with a long-term COVID-19 infection (4 months) where 18 de novo mutation occureed overall. Patient was taking rituximab, the B-cell-depleting agent, and had no detectable neutralizing antibody response." "" "" "" "Bazykin" "2021" "https://virological.org/t/emergence-of-y453f-and-69-70hv-mutations-in-a-lymphoma-patient-with-long-term-covid-19/580" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22924,22924,22925,22926" "L455S,L455S,L455S,L455S" ",NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C" "YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.45 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22925" "L455A" "" "YP_009724390.1:p.Leu455Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.58 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22926,22927,22927,22928,22930,22930" "F456L,F456L,F456L,F456L,F456L,F456L" "NC_045512.2:g.1366T>C,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>A,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>G,NC_045512.2:g.1368T>A" "YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This double substitution reduces neutralization by RBD-specific mAbs from different clusters, specifically, the cluster I mAb COVA2-29, cluster III mAb COVA2-07 and cluster VI mAb COVA1-12. For COVA1-12 all neutralization activity is abolished, while COVA2-07 activity is just below the level required to calculate an IC50 value." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Moderate in vitro selection against class 1 (Spike 'up' conformation) antibodies C683 and C664. Unclassified antibody C666 selected for the emergence of the F456V mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22936" "K458N" "NC_045512.2:g.1374G>T" "YP_009724390.1:p.Lys458Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.09 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22939,22942,22942,22942" "N460K,N460K,N460K,N460K,N460K" "" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460Y" "NC_045512.2:g.1378A>T" "YP_009724390.1:p.Asn460Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mild escape mutant emergent for class 1 antibody C613 in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22941" "N460I" "NC_045512.2:g.1379A>T" "YP_009724390.1:p.Asn460Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22941" "N460S" "NC_045512.2:g.1379A>G" "YP_009724390.1:p.Asn460Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22964" "I468V" "NC_045512.2:g.1402A>G" "YP_009724390.1:p.Ile468Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22964" "I468V" "NC_045512.2:g.1402A>G" "YP_009724390.1:p.Ile468Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22976" "I472V" "NC_045512.2:g.1414A>G" "YP_009724390.1:p.Ile472Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb X593 (on D614G background)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22976" "I472V" "NC_045512.2:g.1414A>G" "YP_009724390.1:p.Ile472Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~50x binding against this isolated mutation. Estesevimab lost ~8x binding against this isolated mutation. Sotrovimab lost ~30x binding against this isolated mutation. Tixagevimab lost ~15x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some class 1 (Spike 'up' conformation) antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C102, C105 and C144 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding, with increasing proportion in subsequent rounds." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 2.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows some resistence across all antibodies tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "While S477N itself is highly resistent to a broad range of monoclonal antibodies, combined with S514F high neutralization is restricted to only three antibodies in a broad screen." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of mild positive and negative changes in neutralization capability of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), 10 show low neutralization." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.22 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 host variant dependency" "" "" "This mutation's measured interaction affinity with ACE2:p.S19P (0.03% minor allele frequency, found almost exclusively in African/African-Americans in the GnomAD database) was significantly lower than the predicted value, indicating that these mutations were not independent. This is consistent with the fact that the ACE2 residue S19 is adjacent to RBD residue S477 in the contact interface." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility." "" "" "" "Singh" "2021" "https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility." "" "" "" "Singh" "2021" "https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-07, SARS2-16 and SARS2-19 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-07 and SARS2-16 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 11 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,22995,23042" "T478K,T478K,S494P" "NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1480T>C" "YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Combination of RBD mutations appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome complicated by diffuse alveolar hemorrhage, who was receiving anticoagulation therapy, glucocorticoids, cyclophosphamide, and intermittent rituximab and eculizumab." "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23011,23012" "S477N,E484K,E484K" "" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~10x binding against this double mutation. Tixagevimab lost ~16x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23401,23402,23403,23403" "S477N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "11 cases of re-infection with the ""Marseille-4"" variant found within 1028 positive tests, where all of the earlier infections were from different strains. This lineage is also characterized by N:p.M234I;A376T" "" "" "" "Fournier" "2021" "https://doi.org/10.1016/j.ijid.2021.03.068" "doi:10.1016/j.ijid.2021.03.068" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23401,23402,23403,23403" "S477N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was neutralized slightly less than D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23401,23402,23403,23403" "S477N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23401,23402,23403,23403" "S477N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Compared to the clade 20A strains that predominated during phase 1 between March and May 2020, the Marseille-4 variant (characterized by this mutation plus N:p.M234I;A376T) was associated with a lower frequency of cough, rhinitis, and olfactory and gustatory disorders. By contrast, hypoxemia was more frequent in patients infected with the Marseille-4 variant." "" "" "" "Fournier" "2021" "https://doi.org/10.1016/j.ijid.2021.03.068" "doi:10.1016/j.ijid.2021.03.068" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23003" "N481Y" "NC_045512.2:g.1441A>T" "YP_009724390.1:p.Asn481Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Minor variant in initial round of in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009" "V483L" "NC_045512.2:g.1447G>C" "YP_009724390.1:p.Val483Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, 1B07, SARS2-32, SARS2-35 and SARS2-07 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Remarkably, several of the E484 escape mutants were resistant to neutralization at the highest concentration (1:80 initial dilution) of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), all but one show major resistance." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in all 4 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 152 virus from a chronically infected patient: although mAb C1A-B12 had no activity against this pseudotype, all three affinity optimized versions were active; the antibody containing the most mutations, C1A-B12.3, was the most potent (IC50 <0.5 μg/mL)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This Spike pseudotype for Day 152 virus from a chronically infected patient was completely resistent to REGN10933." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 152 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 152 S pseudotype was resistant to neutralization." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "3rd exposure to antigen by Delta (B.1.617.2) (n=24) breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a 3rd mRNA vaccine dose in individuals aged 21 –63 years, median age=30 years. Data collected 5.5 months after 2nd vaccination." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous." "" "" "" "Braeye" "2022" "https://doi.org/10.1101/2022.05.09.22274623" "doi:10.1101/2022.05.09.22274623" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In sera from 17 sero-positive blood donors, and 18 months post-infection (May 2020) sera from 17 health care workers in Sweden, a 40x drop in neutralization by Omicron (B.1.1.529) pseudotyped lentivirus was observed in HEK293T cells using the First WHO International Standard (20/136). Median IC50 reduction was ~6x for the blood donors, and ~4.5x for the health care workers." "" "" "" "Sheward" "2021" "https://drive.google.com/file/d/1CuxmNYj5cpIuxWXhjjVmuDqntxXwlfXQ/view" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous." "" "" "" "Braeye" "2022" "https://doi.org/10.1101/2022.05.09.22274623" "doi:10.1101/2022.05.09.22274623" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23071,23071,23074,23074,23075,23075,22992,23060,23061,23062,23062,23063,23063" "E484A,E484A,E484A,E484A,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,S477N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using molecular dynamics simulation, ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations." "" "" "" "Zhang" "2022" "https://doi.org/10.1101/2022.06.05.493249" "doi:10.1101/2022.06.05.493249" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23012" "E484R,E484R" "" "YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This is a two point mutation change giving this position the highest possible fitness, has higher affinity than circulating E484K variant." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23012" "E484R,E484R" "" "YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23012" "E484R,E484R" "" "YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23012" "E484R,E484R" "" "YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23012" "E484R,E484R" "" "YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This is a two point mutation change giving this position the highest possible fitness, has higher affinity than circulating E484K variant." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23012" "E484R,E484R" "" "YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "As measured by surface plasmon resonance, RBD with the E484K mutation alone showed a mean 19.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Individual variants appearing at <=30% frequency at day 21 in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then appearing all at >95% frequency at day 27." "" "" "" "Chen" "2021" "https://doi.org/10.1101/2021.04.08.21254791" "doi:10.1101/2021.04.08.21254791" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in binding efficiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus)" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "E484K pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed a mean 2.8x decrease in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported moderate increase in affinity compared to wild-type RBD on the cell surface (Kd = 38.5nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Monoclonal antibodies 13G9 and 58G6 maintain fairly high neutralization potency, compared to others interfacing with E484K." "" "" "" "Li" "2021" "https://doi.org/10.1101/2021.04.19.440481" "doi:10.1101/2021.04.19.440481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Of 50 mAbs tested, major loss of neutralization observed for S2N28, S2X615, S2N12, S2X192, S2H7, S2X16, S2X58, S2H70, S2X613, S2D19, S2N22, S2D32, S2H58, S2M11, S2D106, S2X30." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Analyzing responses to the E484K mutation seen in B.1.351 and P.1 variants, we noted that it did not fall in a region predicted to bind the HLAII alleles tested (table S4). The mutation appeared to have no substantial or differential impact on T cell responses." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~16x binding against this isolated mutation. Casirivimab lost ~16x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, ELISA tests show 10x reduced efficacy of a majority of isolated antibodies, but only a modest decrease for vaccine plasma overall." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers of non-human primate sera after one or two doses of Ad26.COV2.S (Jannsen vaccine) against the variants containing the E484K substitution in the RBD were present but reduced (fold reduction between 3.35–7.78, 95% confidence interval all above twofold difference, one-sample t test)." "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Human sera from 5 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) neutralized this variant 3.4x less relative to reference USA-WA1/2020 strain. 8 convalescent plasma with weak IgG ELISA titre neutralized this variant 2.4x less relative to reference USA-WA1/2020 strain. One plasma failed to neutralize at all. 11 convalescent plasma with moderate IgG ELISA titre neutralized this variant 4.2x less relative to reference USA-WA1/2020 strain. 11 convalescent plasma with high IgG ELISA titre neutralized this variant 2.6x less relative to reference USA-WA1/2020 strain." "" "" "" "Jangra" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-02, 1B07, SARS2-16, SARS2-32, SARS2-35 and 2B04 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 15/20 convalescent sera was significantly lower against this pseudotyped virus model" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in all 4 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "This mutation occurred in 100% of sequenced virions after 12 passages and led to a 4-fold decrease in convalescent plasma neutralization activity" "" "" "" "Andreano" "2020" "https://doi.org/10.1101/2020.12.28.424451" "doi:10.1101/2020.12.28.424451" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape due to E484K [given Dec 2020-Apr 2021 time frame of the study, this is assumed to entail both Beta and Gamma lineages]." "" "" "" "Chung" "2021" "https://doi.org/10.1136/bmj.n1943" "doi:10.1136/bmj.n1943" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.3x reduction in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.6 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody VH-Fc ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "The only mutation in the B.1.351 lineage that appears to contribute to neutralization reduction (~1.7x across 10 convalescent sera from April 2020 infectees)" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus)" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2 antibodies C627, C602, C671, C643, and class 2/3 antibody C603 selected for the emergence of the E484K mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Multiple individuals in two related households were infected with a newly acquired E484K mutation within the B.1.311 lineage. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient's quarantine period." "" "" "" "Sabin" "2021" "https://doi.org/10.1101/2021.10.02.21264415" "doi:10.1101/2021.10.02.21264415" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012" "E484K,E484K" ",NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484K conferred a ten-fold reduction in neutralisation by vaccine sera." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,22597,22597,22599" "E484K,E484K,R346K,R346K,R346K" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E484K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,22810,22810,22811,22812,22813,22813,22813" "E484K,E484K,K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~32x binding against this double mutation. COR-101 lost ~160x binding against this double mutation. Casirivimab lost ~16x binding against this double mutation. Estesevimab lost ~32x binding against this double mutation. Regdanvimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,22810,22810,22811,22812,22813,22813,22813,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "E484K,E484K,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~13x more infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,22810,22810,22811,22812,22813,22813,22813,23399,23401,23401,23402,23403,23403" "E484K,E484K,K417N,K417N,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Approximately as infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of the individual variants)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063" "E484K,E484K,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.5 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In the case of VOC B.1.1.7+E484K, the addition of the E484K mutation to N501Y further increased the affinity, to ~15 fold higher than WT RBD (KD ~5 nM), by further increasing the k(on) as measured by surface plasmon resonance. Because the higher k(on) could result in mass transfer limiting binding, we confirmed that the kinetic measurement for this variant was not substantially affected by varying levels of immobilization." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Omicron Molnupiravir (MK-4482) had no statistically significant change." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.025x fold change in IC50 in B.1.1.529 Omicron" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)]" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.0015x fold change in IC50 in B.1.1.529 Omicron" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.5 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.4 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 20 sera from BNT162b2 mRNA vaccine inoculated participants, 6 displayed mild (2x) reductions in neutralization. This variant combination showed the highest reduction, but the magnitude of the differences was small compared to the >4x differences in HA-inhibition titers that have been used to signal potential need for a strain change in influenza vaccines." "" "" "" "Xie" "2021" "https://doi.org/10.1038/s41591-021-01270-4" "doi:10.1038/s41591-021-01270-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)]" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Protection against symptomatic infection caused by Beta/Gamma (assumed by combined presence of N501Y and E484K) was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%)." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Viral load from oral swabs from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Viral load from lung tissue from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Omicron neutralizing antibodies is 0.686x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~100x folds more significant in 3 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Omicron neutralizing antibodies is 0.722x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~17.5x folds more significant in 9 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.4 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Values taken 28 days after booster dose was given for BBIBP-CorVvaccine to 390 participants with 130 participants in the 0-14d-10m, 0-21d-10m and 0-28d-10m group. The geometric mean titers (GMT) of neutralizing antibody in 0-28d-10m and 0-21d-10m group were significantly higher than 0-14d-10m group at month 3, month 6 and month 10 after the second dose. A sharply decrease by 4.85-fold (GMT: 94.4-20.3), 4.67-fold (GMT: 134.4-28.8) and 4.49-fold (GMT: 145.5-32.4) was observed from day 28 to month 10 after the second dose in 0-14d-10m, 0-21d-10m and 0-28d-10m group, respectively, and they had similar decline kinetics." "" "" "" "Yao T" "2022" "https://doi.org/10.1101/2022.06.22.22276690" "doi:10.1101/2022.06.22.22276690" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied]" "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~11x, Vero ~10x, and Calu-3 ~11x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~12x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of 501 and 484)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.618 was 2.7-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 3-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The estimated vaccine effectiveness against R.1 strain SARS-CoV-2 infection among residents in a Kentucky skilled nursing facility was 66.2% (95% CI = 40.5%–80.8%) and among health care workers was 75.9% (95% CI = 32.5%–91.4%) in the cohort of only those 14d+ post-vaccination Pfizer booster dose. VE against symptomatic COVID-19 was 86.5% (95% CI = 65.6%–94.7%) among residents and 87.1% (95% CI = 46.4%–96.9%) among HCP. VE against hospitalization was 94.4% (95% CI = 73.9%–98.8%) among residents; no HCP were hospitalized. Three residents died, two of whom were unvaccinated (VE = 94.4%; 95% CI = 44.6%–99.4%)." "" "" "" "Cavanaugh" "2021" "https://doi.org/10.15585/mmwr.mm7017e2" "doi:10.15585/mmwr.mm7017e2" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Pseudotyped viruses for B.1.618 was 2.5-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. [details on the convalescent patient sera collection are not abundantly clear in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403,25088" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,V1176F" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped P.2 virus has reduced neutralization activity vs wild type: 5.8x (30 sera Pfizer median 9 days post 2nd dose) and 2.9x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403,25088" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,V1176F" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the P.1 & P.2 lineages of SARS-CoV-2 in Brazil. The Brazilian arm of the Phase 3 double blind study showed severe/critical disease VE of 81.9% (95% CI: 17.0-98.1), and moderate to severe/critical disease VE of 66.2% (95% CI: 51.0-77.1). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 69.3% of mostly severe infections sequenced as of this report, 69.4% were of P.2 lineage [defining lineage SNPs reported here]." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403,25088" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,V1176F" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs]" "" "" "" "Sapkal" "2021" "https://doi.org/10.1101/2021.04.30.441559" "doi:10.1101/2021.04.30.441559" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23011,23012,23399,23401,23401,23402,23403,23403,25088" "E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,V1176F" "" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs]" "" "" "" "Sapkal" "2021" "https://doi.org/10.1101/2021.04.30.441559" "doi:10.1101/2021.04.30.441559" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484T" "" "YP_009724390.1:p.Glu484Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 3 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, E484Q shows a notably resistant profile, comparable to or even more resistant than E484K at later time points (i.e. more resistant to immune cell somatic mutation evolution), see Figure 5a,b. Subject C 32 days post-infection showed >>10 fold reduction in neutralization, reducing to ~10-fold by day 104. Subject B 26 days post-infection showed ~10 fold reduction in neutralization, reducing to ~4x at day 113. Notably, Subject B also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 32, and no E484K immune escape at day 104. Subject I 26 days post-infection showed ~10 fold reduction in neutralization, with no reduction in escape at day 102. Notably, Subject I also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 26, and no E484K immune escape at day 102." "" "" "" "Greaney" "2021" "https://doi.org/10.1016/j.chom.2021.02.003" "doi:10.1016/j.chom.2021.02.003" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a 10x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">20% (ELISA significance threshold) drop in antibody binding by this variant against monoclonal antibody VH-Fc ab8." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~20x binding against this isolated mutation. Casirivimab lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484T" "" "YP_009724390.1:p.Glu484Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484T" "" "YP_009724390.1:p.Glu484Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23401,23402,23403,23403" "E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~4x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23401,23402,23403,23403" "E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, RBD-specific mutation E484Q did not significantly confer infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23401,23402,23403,23403" "E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23401,23402,23403,23403" "E484Q,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 1.34x drop in neutralization (NT50) [mostly from a single serum]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23017,23018" "F486P,F486P" "" "YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23017,23018" "F486P,F486P" "" "YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.22 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23017,23018" "F486P,F486P" "" "YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23017,23018" "F486P,F486P" "" "YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutation causes a greater than 100x fold change in IC50 of Ensovibep." "" "" "" "Rothenberger" "2021" "https://doi.org/10.1101/2021.02.03.429164v4" "doi:10.1101/2021.02.03.429164v4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486A" "" "YP_009724390.1:p.Phe486Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486H" "" "YP_009724390.1:p.Phe486His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.05 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed in 4 separate mink farms in Denmark, but not humans, potential adaptation (diff set of farms than N501T)." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486A" "" "YP_009724390.1:p.Phe486Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Most effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutation causes a greater than 100x fold change in IC50 of Ensovibep." "" "" "" "Rothenberger" "2021" "https://doi.org/10.1101/2021.02.03.429164v4" "doi:10.1101/2021.02.03.429164v4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-07, SARS2-19, 1B07, SARS2-16 and 2B04 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "IC50 relative to wildtype drops ~8x in neutralization efficiency between 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.13 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 1 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed striking resistance with only 38% neutralization at the highest concentration tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">60% drop in antibody binding (ELISA) by this variant against monoclonal antibody VH-Fc ab8." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Modest decrease in in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 5 antibodies." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019,23019" "F486S,F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C," "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23023" "N487K" "NC_045512.2:g.1461T>G" "YP_009724390.1:p.Asn487Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, high ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Based on structural modelling, this change detected on day 128 sequencing in a chronically infected patient would alter an extensive network of polar interactions with antibody residue R94VH, a germline antibody residue that is conserved in all of the potent VH3-53/3-66-derived antibodies isolated from a convalescent donor 5 weeks after infection." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.11 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (3 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2/3 mAb C603 modestly selected for the emergence of this mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 3 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-32." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23029,23030,23031,23031" "F490S,F490S,F490S,F490S,F490S,F490S" "" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23062,23063,23063" "Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 146 virus from a chronically infected patient: resistant to neutralization by mAb C1A-B12, and was still resistant to the affinity enhanced antibodies derived from it (i.e. no affinity maturation effect on neutralization)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23062,23063,23063" "Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This Spike pseudotype for Day 146 virus from a chronically infected patient was completely resistent to REGN10933. The variant had a 4-fold decrease in REGN10987 neutralization sensitivity (2nd component of the Regeneron mAb cocktail)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23062,23063,23063" "Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 146 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 146 S pseudotype was resistant to neutralization." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs X593, 261-262, H4, and P2B-2F6" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) resistant to 3 individual sera at >4x" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490P" "" "YP_009724390.1:p.Phe490Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490P" "" "YP_009724390.1:p.Phe490Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490V" "NC_045512.2:g.1468T>G" "YP_009724390.1:p.Phe490Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 23% of supernatant sequences) after C121 monoclonal antibody assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490P" "" "YP_009724390.1:p.Phe490Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Dominant (70%) in day 21 of prolonged infection in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then nearly disappearing (<5%) by day 27." "" "" "" "Chen" "2021" "https://doi.org/10.1101/2021.04.08.21254791" "doi:10.1101/2021.04.08.21254791" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in binding efficiency vs wild type for mAbs CB6/LY-CoV16 and LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23039,23040" "Q493R,Q493R,Q493R" "" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2 mAb C627 modestly selected for the emergence of this mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-01 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using molecular dynamic simulation, the mildly (~1kcal/mol) enhanced binding energy of this variant is primarily contributed by Tyr505 (−4.98 kcal/mol) which is now involved in a strong hydrogen bonding network with Arg393. Another important energetic contribution comes from the altered orientation of Tyr41 which is now involved with two hydrogen-bonding interactions with Asp355 and Thr500." "" "" "" "" "2021" "https://doi.org/10.1016/j.bbrc.2021.01.035" "doi:10.1016/j.bbrc.2021.01.035" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 2 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, S484P shows a slightly resistant profile across both timepoints (i.e. resistant to immune cell somatic mutation evolution)" "" "" "" "Greaney" "2021" "https://doi.org/10.1016/j.chom.2021.02.003" "doi:10.1016/j.chom.2021.02.003" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Regdanvimab lost ~32x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Minor variant selected in late rounds of an in vitro evolution experiment for ACE2 binding. Shown to increase the thermostability but decrease the association rate constant of the RBD to ACE2" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23048" "G496S" "NC_045512.2:g.1486G>A" "YP_009724390.1:p.Gly496Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063" "Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. The extent of affinity increase with Q498R and N501Y is not exactly quantified, as E484K always emerged with this duo during in vitro evolution." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.69 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In 30 samples collected 111 to 260 days post onset of symptoms, the covalescent plasma can neutralize both the reference USA-WA1/2020 strain and the mouse adapted strain that contains the N501Y spike mutation with similar efficiency." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation alone accounts for most of the increased infectivity of the Alpha variant, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters, and Vero E6 (NHP) and Calu-3 (human) cell lines." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.03.08.434499" "doi:10.1101/2021.03.08.434499" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slightly increased infection rate amongst the cells. [in what is essentially a replicate experiment in the same paper, because each B.1.351 lineage variant was independetly evaluated and N501 is in both lineages, a significant decrease was observed, therefore the error bars described in this paper should be interpreted carefully]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "0.7x reduction in neutralization by key variant in several variants of concern in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Human sera from 6 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) can neutralize both the reference USA-WA1/2020 strain and the mouse adapted SARS-CoV-2 strain that contains the N501Y spike mutation with similar efficiency." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape by lineage Alpha [defined here as N501Y positive, but E484K negative]." "" "" "" "Chung" "2021" "https://doi.org/10.1136/bmj.n1943" "doi:10.1136/bmj.n1943" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome" "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a modest decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Contrary to other reports on N501Y containing lineages (i.e. with additional mutations), N501Y alone may have an even greater affinity for a human monoclonal antibody specific for wild type. These results suggest that the individual N501Y mutation does not contribute to altered viral properties by itself, but may contribute to a collective conformational shift produced by multiple mutations." "" "" "" "Klegerman" "2021" "https://doi.org/10.1101/2021.04.26.441517" "doi:10.1101/2021.04.26.441517" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x)" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.2x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 and day 14 post-2nd dose) against a recombinant single variant virus (modified replicating WA-1 cDNA clone) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In silico methods (PyMOL and PDBePISA) involving mutagenesis (N501Y mutation) and interface analysis focusing on the Spike RDB-ACE2 interaction showed that the SARS-CoV-2 N501Y mutant (lineage B.1.1.7) establishes a more significant number of interactions relating to the mutant residue Y501 (Spike RDB) with residues Y41 and K353 (ACE2). This finding shows that the increased infectivity of SARS-CoV-2 lineage B.1.1.7 is associated with the interaction force between the Spike RBD Y501 mutant residue with the ACE2 receptor, which in this strain is increased." "" "" "" "" "2021" "https://doi.org/10.1101/2020.12.29.424708" "doi:10.1101/2020.12.29.424708" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Of 50 mAbs tested, major loss of neutralization observed for S2X128, S2D8, S2X192, S2D19, S2H14, S2H19." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x)" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C663, and to a lesser extent C613." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Utilizing shark derived vnarbodies, S375F mutation on Omicron RBD disrupts the structure of β-strand, which inhibits binding with 20G6. 20G6 binds to a hidden epitope on RBD which is highly conserved in sarbecoviruses." "" "" "" "Feng" "2022" "https://doi.org/10.1002/smtd.202200387" "doi:10.1002/smtd.202200387" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The N501Y mutation had the biggest effect on ACE2 affinity of any VOC mutation tested, increasing the affinity ~10 fold to KD ~7 nM, by increasing the k(on) ~1.8 fold and decreasing the k(off) by ~ 7 fold as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "As measured by surface plasmon resonance, RBD with the N501Y mutation alone showed a mean 2.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Vaccinated, but not post-infection sera, show decreased average T cell response to an N501Y peptide. When we primed transgenic mice expressing human HLA-DRB1*0401 with the Wuhan Hu-1 peptide pool, T cell responses to the B.1.1.7 variant peptide pool were significantly reduced (p = 0.0286). Furthermore, the T cell response to the spike N501Y mutation common to all three of the current VOC was ablated." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The most frequent RBM mutation N501Y (165,519 instances) makes defective the atypical N-glycosylation sequon NGV 501-503, becoming a key RBM position for the interaction with hACE2-binding hotspot 353." "" "" "" "Gamez" "2021" "https://doi.org/10.1101/2021.04.09.439154" "doi:10.1101/2021.04.09.439154" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "Variant within the six key residues in the receptor binding domain (RBD). Independently reported in UK, Australia (same origin as UK), and South Africa (independent origin)." "" "" "" "Flores-Alanis" "2021" "https://doi.org/10.3390/pathogens10020184" "doi:10.3390/pathogens10020184" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~8x binding against this isolated mutation. Regdanvimab lost ~6x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Lowered the neutralization potency of mAb COVA1-12 to the limit of the assay. Decrease in potency was observed against the N501Y pseudotype for the cluster IX mAb COVA2-17." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,22810,22810,22811,22812,22813,22813,22813" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~20x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~6x binding against this double mutation. M396 lost ~10x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,22810,22810,22811,22812,22813,22813,22813,23011,23012" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In post-vaccination sera from individuals who received one (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) of the BNT162b2 Pfizer vaccine, an average 6.8x reduction in neutralization efficacy of this B.1.351 key variants pseudotype lentivirus vs D614G was observed." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,22810,22810,22811,22812,22813,22813,22813,23011,23012" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "~7x reduction in neutralization by key B.1.351 lineage RBD variant combination in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Two of the cohort showed no neutralization against this variant." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23011,23012" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~64x binding against this double mutation. COR-101 lost ~50x binding against this double mutation. Casirivimab lost ~250x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~32x binding against this double mutation. Tixagevimab lost ~10x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23271" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Partial sequencing of S gene reveals two cases of probable early 2021 B.1.1.7 lineage reinfection from non-B.1.1.7 original cases in Lombardy, with 45 to 90 days between infections (less than the typical 90 day guideline for this call). Patients were 56 and 58yo, immunocompenent, with one a former smoker with obesity and dyslipidemia. One case required intubation during first infection, but presented with mild symptoms upon reinfection. The other case convalesced at home during the first episode, but required CPAP support in the subacute clinical unit upon reinfection." "" "" "" "Novazzi" "2021" "https://doi.org/10.1002/jmv.27066" "doi:10.1002/jmv.27066" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed no change in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~9x, Vero ~8x, and Calu-3 ~8x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~13x, Vero ~10x, and Calu-3 ~10x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells for ACE2 affinity changes vs D614G alone, showing a ~70% drop in IC50 (i.e. increased affinity)." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H (""Ohio"") lineage was neutralized similarly to D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525" "N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23071,23071,23074,23074,23075,23075" "Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed first in a single tiger (cohort of 5), potential adaptation." "" "" "" "McAloose" "2020" "https://doi.org/10.1128/mBio.02220-20" "doi:10.1128/mBio.02220-20" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23071,23071,23074,23074,23075,23075" "Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23075" "Y505Q" "" "YP_009724390.1:p.Tyr505Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23102" "S514T" "NC_045512.2:g.1540T>A" "YP_009724390.1:p.Ser514Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23108" "E516Q" "NC_045512.2:g.1546G>C" "YP_009724390.1:p.Glu516Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23115" "L518Q" "NC_045512.2:g.1553T>A" "YP_009724390.1:p.Leu518Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23120" "A520S" "NC_045512.2:g.1558G>T" "YP_009724390.1:p.Ala520Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "CR3022 (SARS-targeting mAb) cross-reactivity lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23148" "K529T" "NC_045512.2:g.1586A>C" "YP_009724390.1:p.Lys529Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant raises PIWAS epitope score from 3.6% to 6.2% (improved immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated that there is very little free energy change (ddG. -0.02 kcal/mol) for this variant (i.e. approx. same stability as wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing statistically significant increased infection rate amongst the cells." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23373" "T604I" "NC_045512.2:g.1811C>T" "YP_009724390.1:p.Thr604Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a lentivirus virus pseudotyped with D614G Spike, sera from vaccinated individuals who received the second dose (9–11 days post-second dose of Pfizer) exhibited a robust neutralizing potential, with a mean NT50 value of 99,000. This was an average of a 2-fold increase, relative to sera drawn from the individuals who received one dose of vaccination—mean NT50 dilution of 51,300. Importantly, a 6-fold increase in mean NT50 dilution was obtained when sera from the first vaccination dose was compared to convalescent sera from cohort with severe disease (NT50 51,000 vs 8,700) 21 to 63 days post-onset." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Weissman" "2020" "https://doi.org/10.1101/2020.07.22.20159905" "doi:10.1101/2020.07.22.20159905" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 1.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation (a.k.a. ""Doug"") outside the receptor binding domain, while highly favorable to improved human-human transmission, decreases transduction in naked mole-rat (Heterocephalus glaber) fibroblast and Japanese pipistrelle bat (Pipistrellus abramus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to wild type, D614G showed increased infectivity (ie. cold stability) after storage at -20°C for up to 30 days." "" "" "" "Huang" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 conferred a nearly two-fold infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 2.5 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD mutation conferred a 4.85x drop in neutralization (NT50)." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In four cell lines (including 293T-hACE2 cells), this mutation combination increases infectivity vs D614G alone" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission." "" "" "" "Plante" "2020" "https://doi.org/10.1038/s41586-020-2895-3" "doi:10.1038/s41586-020-2895-3" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.35x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses." "" "" "" "Ozono" "2020" "https://doi.org/10.1038/s41467-021-21118-2" "doi:10.1038/s41467-021-21118-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a slight decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses." "" "" "" "Ozono" "2020" "https://doi.org/10.1038/s41467-021-21118-2" "doi:10.1038/s41467-021-21118-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The increased transduction with Spike D614G ranged from 1.3- to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2 and from 1.5- to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction." "" "" "" "Daniloski" "2021" "https://doi.org/10.7554/eLife.65365" "doi:10.7554/eLife.65365" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped D614G virus has reduced neutralization activity vs wild type: 1.2x (37 sera Pfizer median 9 days post 2nd dose, 37 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.05x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.45x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.43x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.97x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Weissman" "2020" "https://doi.org/10.1101/2020.07.22.20159905" "doi:10.1101/2020.07.22.20159905" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.53x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Studying 94 COVID-19 extended infection cases with genomics April 1 to October 17, 2020, one case developed 23 mutations in a 19 day period, including this combination in Spike." "" "" "" "Landis" "2021" "https://doi.org/10.1101/2021.05.08.21256775" "doi:10.1101/2021.05.08.21256775" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403" "D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21575" "D614G,D614G,D614G,D614G,D614G,D614G,L5F" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.23x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21575" "D614G,D614G,D614G,D614G,D614G,D614G,L5F" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.1x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21575" "D614G,D614G,D614G,D614G,D614G,D614G,L5F" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21575,21846,22317,22319,22320,23011,23012,23664" "D614G,D614G,D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,E484K,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.526) showed a 1.02x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21575,21846,22317,22319,22320,23011,23012,23664" "D614G,D614G,D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,E484K,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.526) showed a 1.78x increase in binding (KD) relative to D614G, even though each variant independently decreases binding." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21575,21846,22317,22319,22320,23011,23012,23664" "D614G,D614G,D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,E484K,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.526) showed a 1.34x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21600" "D614G,D614G,D614G,D614G,D614G,D614G,S13I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.42x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21600" "D614G,D614G,D614G,D614G,D614G,D614G,S13I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21600" "D614G,D614G,D614G,D614G,D614G,D614G,S13I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21600,22018,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.429 aka Epsilon) showed a 2.82x increase in binding (KD) relative to D614G, indicating a strong marginal effect for L452R." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21600,22018,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. [Stark contrast to 2.15x increase in binding by convalescent plasma 8 months post infection, presumably via memory B cell affinity maturation against L452R effects] 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21600,22018,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, indicating ablated marginal effect from L452R." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614" "D614G,D614G,D614G,D614G,D614G,D614G,L18F" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.07x decrease in binding (KD) relative to D614G. Compare to increased binding in full Spike variant complements for major lineages containing this variant subset: 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614" "D614G,D614G,D614G,D614G,D614G,D614G,L18F" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.30x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.28x increase (B.1.351 aka Beta), and 1.14x decrease (P.1 aka Gamma). 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.17x increase (B.1.351 aka Beta), and 1.47x decrease (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614" "D614G,D614G,D614G,D614G,D614G,D614G,L18F" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.66x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Compare to decreased binding in full Spike variant complements for major lineages containing this variant subset: 0.96x (B.1.351 aka Beta), 0.77x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "D614G,D614G,D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing P.1 aka Gamma) showed a 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "D614G,D614G,D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing P.1 aka Gamma) showed a 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642" "D614G,D614G,D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing P.1 aka Gamma) showed a 4.24x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614,21801,23060,23061,23062,23062,23063,23063,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23664" "D614G,D614G,D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.351 aka Beta) showed a 3.56x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614,21801,23060,23061,23062,23062,23063,23063,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23664" "D614G,D614G,D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing B.1.351 aka Beta) showed a 1.28x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. It shows a 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21614,21801,23060,23061,23062,23062,23063,23063,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23664" "D614G,D614G,D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing B.1.351 aka Beta) showed a 1.04x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, in contrast to the largely positive binding values for each individual mutation that comprises the set." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21621" "D614G,D614G,D614G,D614G,D614G,D614G,T20N" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.96x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21621" "D614G,D614G,D614G,D614G,D614G,D614G,T20N" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.39x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21621" "D614G,D614G,D614G,D614G,D614G,D614G,T20N" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21638" "D614G,D614G,D614G,D614G,D614G,D614G,P26S" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.23x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21638" "D614G,D614G,D614G,D614G,D614G,D614G,P26S" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21638" "D614G,D614G,D614G,D614G,D614G,D614G,P26S" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.58x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.33x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766" "D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.51x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing B.1.1.7 aka Alpha) showed no change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.28x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing B.1.1.7 aka Alpha) showed a 1.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,21761,21761,21762,21762,21762,21763,21763,21764,21765,21766,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.1.7 aka Alpha) had 5.43x increased binding relative to D614G alone." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21801" "D614G,D614G,D614G,D614G,D614G,D614G,D80A" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination showed no change relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21801" "D614G,D614G,D614G,D614G,D614G,D614G,D80A" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21801" "D614G,D614G,D614G,D614G,D614G,D614G,D80A" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.64x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.35x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21846" "D614G,D614G,D614G,D614G,D614G,D614G,T95I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21846" "D614G,D614G,D614G,D614G,D614G,D614G,T95I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21846" "D614G,D614G,D614G,D614G,D614G,D614G,T95I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21974" "D614G,D614G,D614G,D614G,D614G,D614G,D138Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21974" "D614G,D614G,D614G,D614G,D614G,D614G,D138Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.32x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,21974" "D614G,D614G,D614G,D614G,D614G,D614G,D138Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22018" "D614G,D614G,D614G,D614G,D614G,D614G,W152C" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22018" "D614G,D614G,D614G,D614G,D614G,D614G,W152C" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.03x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22018" "D614G,D614G,D614G,D614G,D614G,D614G,W152C" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.15x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22132" "D614G,D614G,D614G,D614G,D614G,D614G,R190S" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.59x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22132" "D614G,D614G,D614G,D614G,D614G,D614G,R190S" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22132" "D614G,D614G,D614G,D614G,D614G,D614G,R190S" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.82x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22206" "D614G,D614G,D614G,D614G,D614G,D614G,D215G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.79x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22206" "D614G,D614G,D614G,D614G,D614G,D614G,D215G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.19x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22206" "D614G,D614G,D614G,D614G,D614G,D614G,D215G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D614G,D614G,D253G,D253G,D253G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.08x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D614G,D614G,D253G,D253G,D253G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D614G,D614G,D253G,D253G,D253G" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22810,22810,22811,22812,22813,22813,22813" "D614G,D614G,D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22810,22810,22811,22812,22813,22813,22813" "D614G,D614G,D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22810,22810,22811,22812,22813,22813,22813" "D614G,D614G,D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N,K417N,K417N" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.76x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.75x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22812,22812" "D614G,D614G,D614G,D614G,D614G,D614G,K417T,K417T" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22812,22812" "D614G,D614G,D614G,D614G,D614G,D614G,K417T,K417T" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.28x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22812,22812" "D614G,D614G,D614G,D614G,D614G,D614G,K417T,K417T" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.05x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.16x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.66x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917" "D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22783,22783,22784,22785,22786,22786,22679,22679,22686,22992,22992,22995,23071,23071,23074,23074,23075,23075" "D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,R408S,S373P,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 78fM for binding to the Omicron BA.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22783,22783,22784,22785,22786,22786,22679,22679,22686,22992,22992,22995,23071,23071,23074,23074,23075,23075" "D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,R408S,S373P,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 4.5-fold lower (95% CI: 4.3x-4.7x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22783,22783,22784,22785,22786,22786,22679,22679,22686,22992,22992,22995,23071,23071,23074,23074,23075,23075" "D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,R408S,S373P,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 3.9x-fold lower (95% CI: 0.14x-0.17x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22917,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22783,22783,22784,22785,22786,22786,22679,22679,22686,22992,22992,22995,23071,23071,23074,23074,23075,23075" "D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,R408S,S373P,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 4.2-fold lower (95% CI: 5.8x-6.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22917,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,22783,22783,22784,22785,22786,22786,22679,22679,22686,22992,22992,22995,23071,23071,23074,23074,23075,23075" "D614G,D614G,D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,R408S,S373P,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 3.9x-fold lower (95% CI: 0.14x-0.18x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23011,23012" "D614G,D614G,D614G,D614G,D614G,D614G,E484K,E484K" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.42x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23011,23012" "D614G,D614G,D614G,D614G,D614G,D614G,E484K,E484K" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23011,23012" "D614G,D614G,D614G,D614G,D614G,D614G,E484K,E484K" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This variant appears twice in the experiments, with slightly different affinities (both ~1.2x decrease in binding relative to D614G) using flow cytometry and ACE2 ectodomains-Fc portion IgG complex." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23060,23061,23062,23062,23063,23063" "D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23060,23061,23062,23062,23063,23063" "D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23060,23061,23062,23062,23063,23063" "D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.52x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis). Compare to full Spike variant complements for major lineages containing this variant subset: 5.43x (B.1.1.7 aka Alpha), 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23271" "D614G,D614G,D614G,D614G,D614G,D614G,A570D" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23271" "D614G,D614G,D614G,D614G,D614G,D614G,A570D" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.18x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23271" "D614G,D614G,D614G,D614G,D614G,D614G,A570D" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.21x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.48x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525" "D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23604,23604" "D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23604,23604" "D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23604,23604" "D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.26x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23604,23604" "D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant change in virus neutralzation by 18 Pfizer two dose vaccinee sera compared to B.1.1.7. [results without including the used mutation A27S likely generalizable, as this is not a lineage defining mutation]" "" "" "" "Zuckerman" "2021" "https://doi.org/10.1101/2021.03.25.21253908" "doi:10.1101/2021.03.25.21253908" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23664" "D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23664" "D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23664" "D614G,D614G,D614G,D614G,D614G,D614G,A701V" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed essentially no change in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23709" "D614G,D614G,D614G,D614G,D614G,D614G,T716I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23709" "D614G,D614G,D614G,D614G,D614G,D614G,T716I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.58x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,23709" "D614G,D614G,D614G,D614G,D614G,D614G,T716I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.12x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24506" "D614G,D614G,D614G,D614G,D614G,D614G,S982A" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24506" "D614G,D614G,D614G,D614G,D614G,D614G,S982A" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.3x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24506" "D614G,D614G,D614G,D614G,D614G,D614G,S982A" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24642" "D614G,D614G,D614G,D614G,D614G,D614G,T1027I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.56x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24642" "D614G,D614G,D614G,D614G,D614G,D614G,T1027I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.69x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24642" "D614G,D614G,D614G,D614G,D614G,D614G,T1027I" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.22x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24914" "D614G,D614G,D614G,D614G,D614G,D614G,D1118H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24914" "D614G,D614G,D614G,D614G,D614G,D614G,D1118H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23401,23402,23403,23403,24914" "D614G,D614G,D614G,D614G,D614G,D614G,D1118H" "" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.96x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23429" "A623T" "NC_045512.2:g.1867G>A" "YP_009724390.1:p.Ala623Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23521,23522,23524,23524,23525,23525" "H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.87 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23521,23522,23524,23524,23525,23525" "H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23521,23522,23524,23524,23525,23525" "H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Six minks were intranasally infected with WA1 isolate, all developed this mutation during infection." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23521,23522,23524,23524,23525,23525" "H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y" "" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain increases the virus transduction rate in tree shrew (Tupaia belangeri), (as it does in humans) according to pseudotyped VSV experiments." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23587,23587,23587" "Q675H,Q675H,Q675H" ",NC_045512.2:g.2025G>C,NC_045512.2:g.2025G>T" "YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly enhanced the ability of the pseudotyped VSV to infect fat-tailed gerbil (Pachyuromys duprasi) kidney cell cultures, with a transduction rate of 13.4%, close to the 15.7% in epithelial-like human Huh-7 cells while starting from a significantly lower wildtype (Wuhan-Hu-1 Spike VSVdeltaG psuedotype) rate." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681R,P681R" "NC_045512.2:g.2042C>G," "YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. [PG: Inferred by conservative AA substitution of described P681H]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic." "" "" "" "Johnson" "2020" "https://doi.org/10.1101/2020.08.26.268854" "doi:10.1101/2020.08.26.268854" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "While the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC)." "" "" "" "Lubinski" "2021" "https://doi.org/10.1101/2021.04.06.438731" "doi:10.1101/2021.04.06.438731" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In the absence of N501Y, this Alpha lineage change in the furin clevage site did NOT show significant increase in infectivity relative to wild type, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.03.08.434499" "doi:10.1101/2021.03.08.434499" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic." "" "" "" "Johnson" "2020" "https://doi.org/10.1101/2020.08.26.268854" "doi:10.1101/2020.08.26.268854" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681R,P681R" "NC_045512.2:g.2042C>G," "YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). [Inference from similar positively charged substitution P681H actually described in the work]" "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 0.9x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry)." "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry)." "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604" "P681H,P681H" ",NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing NO statistically significant infection rate change amongst the cells, suggesting that furin cleavage typically used for cell entry is not affected by this change one amino acid upstream of the RXXR recognition pattern." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23604,23399,23401,23401,23402,23403,23403" "P681R,P681R,D614G,D614G,D614G,D614G,D614G,D614G" "" "YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Quantification of the band intensities showed that the P681R mutation, which lies near the proteolytic processing site, caused a small increase in proteolytic processing as measured by a 2-fold decrease in the ratio of S/S2." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23664" "A701V" "NC_045512.2:g.2102C>T" "YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23664" "A701V" "NC_045512.2:g.2102C>T" "YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.33 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant increases PIWAS epitope score from 0.69% to 2.3% Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain showed a decreased capacity to transduce PK-15 (pig kidney, Sus scrofa) and PaKi (black flying fox kidney, Pteropus alecto) cell line cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed first in a single tiger (cohort of 5), potential adaptation." "" "" "" "McAloose" "2020" "https://doi.org/10.1128/mBio.02220-20" "doi:10.1128/mBio.02220-20" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. T716I was expressed at significantly lower level, accounting for the decreased infectivity of this spike protein. This property may be specific to spike protein biosynthesis in 293T cells and is not likely to reflect the situation in vivo given the reported increase in infectivity of the B.1.1.7 virus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23897" "Q779K" "NC_045512.2:g.2335C>A" "YP_009724390.1:p.Gln779Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 20% appearance in 2 passages against Regeneron monoclonal antibody RGN10989 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23948" "D796H" "NC_045512.2:g.2386G>C" "YP_009724390.1:p.Asp796His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Fatal COVID-19 complications in immunocomprimised patient after immune escape from convalescent plasma" "" "" "" "Kemp" "2020" "https://doi.org/10.1101/2020.12.05.20241927" "doi:10.1101/2020.12.05.20241927" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24000" "S813I" "NC_045512.2:g.2438G>T" "YP_009724390.1:p.Ser813Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb B38" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24077" "D839Y" "NC_045512.2:g.2515G>T" "YP_009724390.1:p.Asp839Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry." "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24077" "D839N" "NC_045512.2:g.2515G>A" "YP_009724390.1:p.Asp839Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry." "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24130" "N856K" "NC_045512.2:g.2568C>A" "YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch." "" "" "" "Lucaci" "2021" "" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24170" "I870V" "NC_045512.2:g.2608A>G" "YP_009724390.1:p.Ile870Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Appeared at same time as T478K,S494P but listed separately due to distance and different domains affected in the Spike (i.e. putatively an independent mutation from a functional standpoint since the former are from S1, the latter from S2)." "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24377,24378,24378" "S939F,S939F,S939F" "NC_045512.2:g.2816C>T,NC_045512.2:g.2816C>T," "YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (70%) increase in infection rate amongst the cells, hence this individual variant is likely to significantly contribute to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 6/20 convalescent sera was significantly lower against this single variant pseudotyped virus model, showing similar patterns to the pseudotyped virus model of B.1.1.7." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24642" "T1027I" "NC_045512.2:g.3080C>T" "YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 1.51 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Mutation is predicted to lose the T cell epitope for people carrying DRB1*0301 and DRB1*0401, but not for example in those who are DRB1*0701 or DRB1*1501 who would be predicted to show an enhanced response. This is also observed in a study of 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25045,25046,25046" "P1162S,P1162S,P1162S" "" "YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25249,25249,25249" "M1229I,M1229I,M1229I" "NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25350" "P1263L" "NC_045512.2:g.3788C>T" "YP_009724390.1:p.Pro1263Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant in the cytoplasmic tail, shown in vitro to increase Spike subunit fusion required for cell entry" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25855" "D155Y" "NC_045512.2:g.463G>T" "YP_009724391.1:p.Asp155Tyr" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "caveolin binding" "" "" "In silico, this mutation is the only one weakening ORF3a's binding affinity for caveolin-1 (essential for entry and endomembrane trafficking of SARS-CoV-2). This mutation is a widespread homoplasy in 20A and 20B lineages." "" "" "" "Gupta" "2021" "https://doi.org/10.1101/2021.03.26.437194" "doi:10.1101/2021.03.26.437194" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26029" "Q213K" "NC_045512.2:g.637C>A" "YP_009724391.1:p.Gln213Lys" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*01:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26029" "Q213K" "NC_045512.2:g.637C>A" "YP_009724391.1:p.Gln213Lys" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*01:01-restricted CD8+ ORF3a epitope, which is otherwise ""consistently dominant and of high magnitude""." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26256" "F4F" "NC_045512.2:g.12C>T" "YP_009724392.1:p.Phe4Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26268,26268,26269,26270" "T9I,T9I,T9I,T9I" ",NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T" "YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~300 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26268,26268,26269,26270" "T9I,T9I,T9I,T9I" ",NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T" "YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26295,26296" "L18I,L18I" ",NC_045512.2:g.52C>A" "YP_009724392.1:p.Leu18Ile,YP_009724392.1:p.Leu18Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (47x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26299" "L19F" "NC_045512.2:g.55C>T" "YP_009724392.1:p.Leu19Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26312" "F23C" "NC_045512.2:g.68T>G" "YP_009724392.1:p.Phe23Cys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~8.8 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26314" "V24M" "NC_045512.2:g.70G>A" "YP_009724392.1:p.Val24Met" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26319" "V25V" "NC_045512.2:g.75A>G" "YP_009724392.1:p.Val25Val" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (45x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26333" "T30I" "NC_045512.2:g.89C>T" "YP_009724392.1:p.Thr30Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26353" "L37F" "NC_045512.2:g.109C>T" "YP_009724392.1:p.Leu37Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26395" "L51I" "NC_045512.2:g.151C>A" "YP_009724392.1:p.Leu51Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (47x overrepresentation vs expected count of ~24 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26416" "V58L" "NC_045512.2:g.172G>C" "YP_009724392.1:p.Val58Leu" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26428" "V62F" "NC_045512.2:g.184G>T" "YP_009724392.1:p.Val62Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (18x overrepresentation vs expected count of ~333 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26442" "N66K" "NC_045512.2:g.198T>G" "YP_009724392.1:p.Asn66Lys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~23 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26447" "S68F" "NC_045512.2:g.203C>T" "YP_009724392.1:p.Ser68Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26447" "S68C" "NC_045512.2:g.203C>G" "YP_009724392.1:p.Ser68Cys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (58x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26456" "P71R" "NC_045512.2:g.212C>G" "YP_009724392.1:p.Pro71Arg" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26466,26467" "V75L,V75L" ",NC_045512.2:g.223G>C" "YP_009724392.1:p.Val75Leu,YP_009724392.1:p.Val75Leu" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (3762.7x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526" "A2S" "NC_045512.2:g.4G>T" "YP_009724393.1:p.Ala2Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (38x overrepresentation vs expected count of ~334 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526" "A2S" "NC_045512.2:g.4G>T" "YP_009724393.1:p.Ala2Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Emergent as 16% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing." "" "" "" "Avanzato" "2020" "https://doi.org/10.1016/j.cell.2020.10.049" "doi:10.1016/j.cell.2020.10.049" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526,26527,26529" "D3H,D3H,D3H" "NC_045512.2:g.7G>C,NC_045512.2:g.7G>C,NC_045512.2:g.7G>C" "YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (227x overrepresentation vs expected count of ~14 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26528,26528,26528" "A2A,A2A,A2A" "NC_045512.2:g.6A>T,NC_045512.2:g.6A>G,NC_045512.2:g.6A>C" "YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (25x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26530" "D3G" "NC_045512.2:g.8A>G" "YP_009724393.1:p.Asp3Gly" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (31x overrepresentation vs expected count of ~53 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26542" "T7I" "NC_045512.2:g.20C>T" "YP_009724393.1:p.Thr7Ile" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26546" "I8I" "NC_045512.2:g.24T>C" "YP_009724393.1:p.Ile8Ile" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~80 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26573,26573,26576,26576,26577,26577" "Q19E,Q19E,Q19E,Q19E,Q19E,Q19E" "" "YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~8 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26620" "C33S" "NC_045512.2:g.98G>C" "YP_009724393.1:p.Cys33Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~32 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26645" "N41N" "NC_045512.2:g.123C>T" "YP_009724393.1:p.Asn41Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (19x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26681" "F53F" "NC_045512.2:g.159C>T" "YP_009724393.1:p.Phe53Phe" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (163x overrepresentation vs expected count of ~567 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26730" "V70L" "NC_045512.2:g.208G>C" "YP_009724393.1:p.Val70Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26748" "I76L" "NC_045512.2:g.226A>C" "YP_009724393.1:p.Ile76Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~9 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26748" "I76V" "NC_045512.2:g.226A>G" "YP_009724393.1:p.Ile76Val" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26749" "I76T" "NC_045512.2:g.227T>C" "YP_009724393.1:p.Ile76Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (19x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26767" "I82T" "NC_045512.2:g.245T>C" "YP_009724393.1:p.Ile82Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (67x overrepresentation vs expected count of ~42 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26767" "I82T" "NC_045512.2:g.245T>C" "YP_009724393.1:p.Ile82Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "homoplasy" "" "" "This mutation presents mainly within the B.1 (44.0%) and B.1.525 (38.1%) lineages. Currently, 99.7% of the B.1.525 lineage isolates carry the M:I82T mutation. While this mutation is scattered across multiple phylogenetic clades, most cases cluster in two recent clades, suggesting a likely selective advantage in certain haplotype backgrounds." "" "" "" "Shen" "2021" "https://doi.org/10.1080/22221751.2021.1922097" "doi:10.1080/22221751.2021.1922097" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26801,26801,26801" "L93L,L93L,L93L" "NC_045512.2:g.279C>G,NC_045512.2:g.279C>A,NC_045512.2:g.279C>T" "YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~628 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26855,26858" "F112F,F112F" "NC_045512.2:g.336C>T,NC_045512.2:g.336C>T" "YP_009724393.1:p.Phe112Phe,YP_009724393.1:p.Phe112Phe" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~463 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26861" "N113N" "NC_045512.2:g.339T>C" "YP_009724393.1:p.Asn113Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (57x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26873" "N117N" "NC_045512.2:g.351C>T" "YP_009724393.1:p.Asn117Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26882,26882" "L120L,L120L" "NC_045512.2:g.360C>A,NC_045512.2:g.360C>T" "YP_009724393.1:p.Leu120Leu,YP_009724393.1:p.Leu120Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26894,26894" "L124L,L124L" "NC_045512.2:g.372C>T,NC_045512.2:g.372C>G" "YP_009724393.1:p.Leu124Leu,YP_009724393.1:p.Leu124Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26895" "H125Y" "NC_045512.2:g.373C>T" "YP_009724393.1:p.His125Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (22x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26895" "H125Y" "NC_045512.2:g.373C>T" "YP_009724393.1:p.His125Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARA_CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26907,26909,26909" "L129L,L129L,L129L" "NC_045512.2:g.385C>T,NC_045512.2:g.387G>A,NC_045512.2:g.387G>T" "YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26927" "E135E" "NC_045512.2:g.405A>G" "YP_009724393.1:p.Glu135Glu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (232x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26951,26951,26951" "V143V,V143V,V143V" "NC_045512.2:g.429G>C,NC_045512.2:g.429G>A,NC_045512.2:g.429G>T" "YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~508 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26966" "H148H" "NC_045512.2:g.444T>C" "YP_009724393.1:p.His148His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26972" "R150R" "NC_045512.2:g.450T>C" "YP_009724393.1:p.Arg150Arg" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~89 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26985" "H155N" "NC_045512.2:g.463C>A" "YP_009724393.1:p.His155Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26987" "H155H" "NC_045512.2:g.465T>C" "YP_009724393.1:p.His155His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27021" "E167Q" "NC_045512.2:g.499G>C" "YP_009724393.1:p.Glu167Gln" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27035,27038" "T172T,T172T" "NC_045512.2:g.516A>G,NC_045512.2:g.516A>G" "YP_009724393.1:p.Thr172Thr,YP_009724393.1:p.Thr172Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27059" "Y179Y" "NC_045512.2:g.537C>T" "YP_009724393.1:p.Tyr179Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27112" "S197T" "NC_045512.2:g.590G>C" "YP_009724393.1:p.Ser197Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (18x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27134" "Y204Y" "NC_045512.2:g.612T>C" "YP_009724393.1:p.Tyr204Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27143" "N207N" "NC_045512.2:g.621C>T" "YP_009724393.1:p.Asn207Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27147" "D209H" "NC_045512.2:g.625G>C" "YP_009724393.1:p.Asp209His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (81x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27367" "Q56X" "NC_045512.2:g.166C>T" "YP_009724394.1:p.Gln56Xaa" "" "open reading frame 6 gene (SARS-CoV-2)" "orf6 gene (SARS-CoV-2)" "open reading frame 6 protein (SARS-CoV-2)" "Orf6 protein (SARS-CoV-2)" "IFN activity" "" "" "The residues listed are determinants of the potent IFN-antagonistic activity of SARS-CoV-2 ORF6 (via blocking mRNA nuclear export)" "" "" "" "Kimura" "2020" "https://doi.org/10.2139/ssrn.3690468" "doi:10.2139/ssrn.3690468" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28144" "L84S" "NC_045512.2:g.251T>C" "YP_009724396.1:p.Leu84Ser" "" "open reading frame 8 gene (SARS-CoV-2)" "orf8 gene (SARS-CoV-2)" "open reading frame 8 protein (SARS-CoV-2)" "Orf8 protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28280" "D3L" "" "YP_009724397.2:p.Asp3Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "subgenomic RNA expression" "" "" "A noncanonical subgenomic RNA which could represent ORF9b is significantly enriched (~16x) in B.1.1.7 SARS-CoV-2 infections, potentially as a result of a triple nucleotide mutation leading to amino acid substitution D3L in nucleocapsid in this lineage which increases complementarity with the genomic leader sequence." "" "" "" "Parker" "2021" "https://doi.org/10.1101/2021.03.02.433156" "doi:10.1101/2021.03.02.433156" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28280" "D3L" "" "YP_009724397.2:p.Asp3Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "At the epitope level, the D3L mutation reduces PIWAS signal in 1.5% of COVID patients (outliers reduce from 2.1% in wild type to 0.5% in mutant). In 3 of these patients (0.5% of the population), that alteration represents the strongest antigen signal and substantially reduces the PIWAS antigen score. In the B1.1.7 lineage this is largely counteracted by the S235F mutation, which increases epitope and antigen scores significantly in two individuals, for a net neutral effect at the population level." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28307,28308,28309,28309,28310,28310,28311,28311" "P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L" "" "YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28307,28308,28309,28309,28310,28310,28311,28311" "P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L" "" "YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13)." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28310" "P13S" "NC_045512.2:g.37C>T" "YP_009724397.2:p.Pro13Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13)." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28310" "P13S" "NC_045512.2:g.37C>T" "YP_009724397.2:p.Pro13Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*27:05." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28769" "T166A" "NC_045512.2:g.496A>G" "YP_009724397.2:p.Thr166Ala" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "Confers a significant PIWAS value decrease (reduced antigenicity)" "" "" "" "Haynes" "2020" "https://doi.org/10.1101/2020.11.23.20235002" "doi:10.1101/2020.11.23.20235002" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28853" "S194T" "NC_045512.2:g.580T>A" "YP_009724397.2:p.Ser194Thr" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28854" "S194L" "NC_045512.2:g.581C>T" "YP_009724397.2:p.Ser194Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "Mutation with a population frequency of 30% in a Mexican dataset, primarily of lineage 20B, but also present in a substantial number of 20A lineage sequences, suggesting convergent evolution." "" "" "" "Barona-Gomez" "2021" "https://doi.org/10.1101/2021.05.18.21256128" "doi:10.1101/2021.05.18.21256128" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28854" "S194L" "NC_045512.2:g.581C>T" "YP_009724397.2:p.Ser194Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In March 2021 this variant had an allele frequency of 47.62 and 7.25% in deceased patients, compared to 35.16 and 3.20% of the same variant in recovered patients, from the Gujarat and global datasets." "" "" "" "Joshi" "2021" "https://doi.org/10.3389/fgene.2021.586569" "doi:10.3389/fgene.2021.586569" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28869" "P199L" "NC_045512.2:g.596C>T" "YP_009724397.2:p.Pro199Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28877,28881" "G204R,G204R" "" "YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "gene expression increase" "" "" "By Western blot, a statistically significant 2x increase in N protein expression in packaging cells was observed using mutant novel virus-like-particles. This did not correlate with luciferase activity (which was not statistically different from D614G wild type)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28879" "S202R" "NC_045512.2:g.606T>G" "YP_009724397.2:p.Ser202Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows major increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881" "R203M" "NC_045512.2:g.608G>T" "YP_009724397.2:p.Arg203Met" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows most increase in RNA content of any N mutation tested, suggesting that this mutation improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881,28877,28881" "R203K,G204R,G204R" "" "YP_009724397.2:p.Arg203Lys,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection in an October 2020 of a 40yo female Brazilian HCW, no hospitalization required in first or second infection. Poor overall genome quality. Genome also has one Spike mutation that would become a defining mutation in lineage P.2, S:p.V1176F" "" "" "" "Amorim" "2021" "https://doi.org/10.3201/eid2706.210558" "doi:10.3201/eid2706.210558" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881,28877,28881" "R203K,G204R,G204R" "" "YP_009724397.2:p.Arg203Lys,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "subgenomic RNA expression" "" "" "This variant shows a significant increase in viral load compared to wild type, but not relative to D614G viruses without the variant in circulating viruses in the Spring of 2020 in Saudia Arabia." "" "" "" "Mourier" "2021" "https://doi.org/10.1101/2021.05.06.21256706" "doi:10.1101/2021.05.06.21256706" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881,28877,28881" "R203K,G204R,G204R" "" "YP_009724397.2:p.Arg203Lys,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "posttranslational modifications" "" "" "This variant, caused by three consecutive SNPs, consistently shows a neighbouring serine 206 (S206) site is highly phosphorylated in the mutant N protein via mass spectrometry." "" "" "" "Mourier" "2021" "https://doi.org/10.1101/2021.05.06.21256706" "doi:10.1101/2021.05.06.21256706" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881,28877,28881" "R203K,G204R,G204R" "" "YP_009724397.2:p.Arg203Lys,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "subgenomic RNA expression" "" "" "This variant, likely arisen by homologous recombination from the core sequence (CS) of the leader transcription-regulating sequence (TRS), generate a novel sub-genomic RNA transcript for the C-terminal dimerization domain. It may also have increased expression of sub-genomic RNA from other open reading frames, based on public data analysis." "" "" "" "Leary" "2021" "https://doi.org/10.1101/2020.04.10.029454" "doi:10.1101/2020.04.10.029454" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881,28877,28881" "R203K,G204R,G204R" "" "YP_009724397.2:p.Arg203Lys,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection in a September 2020 of a 61yo female Brazilian HCW, no hospitalization required in first or second infection. Genome also has one Spike mutation of unknown significance, S:p.Q675H" "" "" "" "Amorim" "2021" "https://doi.org/10.3201/eid2706.210558" "doi:10.3201/eid2706.210558" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881,28877,28881" "R203K,G204R,G204R" "" "YP_009724397.2:p.Arg203Lys,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "subgenomic RNA expression" "" "" "This variant, likely arisen by homologous recombination from the core sequence (CS) of the leader transcription-regulating sequence (TRS), generate a novel sub-genomic RNA transcript for the C-terminal dimerization domain. It may also have increased expression of sub-genomic RNA from other open reading frames, based on public data analysis." "" "" "" "Leary" "2021" "https://doi.org/10.1101/2020.04.10.029454" "doi:10.1101/2020.04.10.029454" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28977" "S235F" "NC_045512.2:g.704C>T" "YP_009724397.2:p.Ser235Phe" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "Substantially increases epitope and antigen scores in 2 of 579 individuals (should increase immune response). In the B1.1.7 lineage this is largely counteracted by the D3L mutation, which decreases PIWAS signal significantly in 1.5% of COVID patients, for a net neutral effect at the population level." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29239,29239" "M322I,M322I" "NC_045512.2:g.966G>A,NC_045512.2:g.966G>T" "YP_009724397.2:p.Met322Ile,YP_009724397.2:p.Met322Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "Agerer" "2021" "https://doi.org/10.1126/sciimmunol.abg6461" "doi:10.1126/sciimmunol.abg6461" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29247" "T325I" "NC_045512.2:g.974C>T" "YP_009724397.2:p.Thr325Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes partial loss of T cell line responsiveness and CTL killing ability by B*40:01-restricted CD8+ N epitope MEVTPSGTWL 322-331." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29247" "T325I" "NC_045512.2:g.974C>T" "YP_009724397.2:p.Thr325Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29266,29266" "L331F,L331F" "NC_045512.2:g.993G>T,NC_045512.2:g.993G>C" "YP_009724397.2:p.Leu331Phe,YP_009724397.2:p.Leu331Phe" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "Agerer" "2021" "https://doi.org/10.1126/sciimmunol.abg6461" "doi:10.1126/sciimmunol.abg6461" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29409" "T379I" "NC_045512.2:g.1136C>T" "YP_009724397.2:p.Thr379Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "335,335" "R24C,R24C" ",NC_045512.2:g.70C>T" "YP_009724389.1:p.Arg24Cys,YP_009724389.1:p.Arg24Cys" "YP_009724389.1:Arg24Cys,YP_009724389.1:Arg24Cys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (25x overrepresentation vs expected count of 514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "347" "V28I" "NC_045512.2:g.82G>A" "YP_009724389.1:p.Val28Ile" "YP_009724389.1:Val28Ile" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (30x overrepresentation vs expected count of 143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "383" "S40P" "NC_045512.2:g.118T>C" "YP_009724389.1:p.Ser40Pro" "YP_009724389.1:Ser40Pro" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~58 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "396" "Q44L" "NC_045512.2:g.131A>T" "YP_009724389.1:p.Gln44Leu" "YP_009724389.1:Gln44Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~19 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "443" "V60I" "NC_045512.2:g.178G>A" "YP_009724389.1:p.Val60Ile" "YP_009724389.1:Val60Ile" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "489" "D75G" "NC_045512.2:g.224A>G" "YP_009724389.1:p.Asp75Gly" "YP_009724389.1:Asp75Gly" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "490,490" "D75E,D75E" "NC_045512.2:g.225T>G,NC_045512.2:g.225T>A" "YP_009724389.1:p.Asp75Glu,YP_009724389.1:p.Asp75Glu" "YP_009724389.1:Asp75Glu,YP_009724389.1:Asp75Glu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~20 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Emergent as 22% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing." "" "" "" "Avanzato" "2020" "https://doi.org/10.1016/j.cell.2020.10.049" "doi:10.1016/j.cell.2020.10.049" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-523) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-517) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 500-523) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,509,518" "M85V,M85V,M85V" "NC_045512.2:g.253A>G,NC_045512.2:g.253A>G,NC_045512.2:g.253A>G" "YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val" "YP_009724389.1:Met85Val,YP_009724389.1:Met85Val,YP_009724389.1:Met85Val" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "508" "H81Q" "NC_045512.2:g.243T>A" "YP_009724389.1:p.His81Gln" "YP_009724389.1:His81Gln" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (30x overrepresentation vs expected count of ~20 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "510" "M85K" "NC_045512.2:g.254T>A" "YP_009724389.1:p.Met85Lys" "YP_009724389.1:Met85Lys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~12 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "561" "R99H" "NC_045512.2:g.296G>A" "YP_009724389.1:p.Arg99His" "YP_009724389.1:Arg99His" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "563" "S100C" "NC_045512.2:g.298A>T" "YP_009724389.1:p.Ser100Cys" "YP_009724389.1:Ser100Cys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (33x overrepresentation vs expected count of ~19 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "592,593" "H110Y,H110Y" ",NC_045512.2:g.328C>T" "YP_009724389.1:p.His110Tyr,YP_009724389.1:p.His110Tyr" "YP_009724389.1:His110Tyr,YP_009724389.1:His110Tyr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (22x overrepresentation vs expected count of ~514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "593" "H110D" "NC_045512.2:g.328C>G" "YP_009724389.1:p.His110Asp" "YP_009724389.1:His110Asp" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~11 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "606" "I114T" "NC_045512.2:g.341T>C" "YP_009724389.1:p.Ile114Thr" "YP_009724389.1:Ile114Thr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (155x overrepresentation vs expected count of ~58 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "657" "A131V" "NC_045512.2:g.392C>T" "YP_009724389.1:p.Ala131Val" "YP_009724389.1:Ala131Val" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "677" "A138T" "NC_045512.2:g.412G>A" "YP_009724389.1:p.Ala138Thr" "YP_009724389.1:Ala138Thr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "761" "S166G" "NC_045512.2:g.496A>G" "YP_009724389.1:p.Ser166Gly" "YP_009724389.1:Ser166Gly" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (132x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "798" "N178S" "NC_045512.2:g.533A>G" "YP_009724389.1:p.Asn178Ser" "YP_009724389.1:Asn178Ser" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" From 4be0584f7c06745dad25efa0a15ddbc02f661c10 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 17:24:39 -0700 Subject: [PATCH 073/161] add 'clade' argument and attribute --- bin/functions.py | 2 +- bin/vcf2gvf.py | 5 ++++- 2 files changed, 5 insertions(+), 2 deletions(-) diff --git a/bin/functions.py b/bin/functions.py index a22e6e07..59dd639b 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -9,7 +9,7 @@ protein_id=;alias_protein_id=;locus_tag=;ps_filter=;ps_exc=; \ mat_pep=;mat_pep_desc=;mat_pep_acc=;ro=;ao=;dp=;sample_size=; \ Reference_seq=;Variant_seq=;nt_name=;aa_name=;hgvs_nt=;hgvs_aa=;hgvs_alias=; \ - vcf_gene=;mutation_type=;viral_lineage=;multi_aa_name=; \ + vcf_gene=;mutation_type=;viral_lineage=;clade=;multi_aa_name=; \ multiaa_comb_mutation=;alternate_frequency=;measured_variant_functional_effect=;inferred_variant_functional_effect=; \ viral_life_cycle_functional_effect=;URL=; \ citation=;comb_mutation=;measured_variant_functional_effect_description=;heterozygosity=; \ diff --git a/bin/vcf2gvf.py b/bin/vcf2gvf.py index 047a69a6..925290c3 100755 --- a/bin/vcf2gvf.py +++ b/bin/vcf2gvf.py @@ -142,7 +142,10 @@ def parse_args(): help='gene positions in JSON format') parser.add_argument('--strain', type=str, default=None, - help='Lineage; user mode is if strain="n/a"') + help='Pangolin lineage; user mode is if strain="n/a"') + parser.add_argument('--clade', type=str, + default=None, + help='Nextclade clade') parser.add_argument("--wastewater", help="Activate wastewater data mode", action="store_true") parser.add_argument('--outgvf', type=str, required=True, From 422f97bfc3d58c9bf13294a4719c66d49bd9fde7 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 18:07:24 -0700 Subject: [PATCH 074/161] add 'functional_annotation_resource' attribute --- bin/addfunctions2gvf.py | 11 ++++++++--- bin/functions.py | 3 ++- 2 files changed, 10 insertions(+), 4 deletions(-) diff --git a/bin/addfunctions2gvf.py b/bin/addfunctions2gvf.py index 18f34dcc..7c1e122c 100755 --- a/bin/addfunctions2gvf.py +++ b/bin/addfunctions2gvf.py @@ -30,6 +30,8 @@ def parse_args(): parser.add_argument('--functional_annotations', type=str, default=None, help='TSV file of functional ' 'annotations') + parser.add_argument('--functional_annotation_resource', type=str, + default='Pokay', help='Functional annotation file identifier; can be versioned (eg. "Pokay_v1.0")') parser.add_argument("--names", type=str, default='n/a', help="Save mutation names without " "functional annotations to " @@ -38,7 +40,7 @@ def parse_args(): return parser.parse_args() # Function to add template annotations to GVF file -def add_template_annotations(gvf, annotation_file): +def add_template_annotations(gvf, annotation_file, annotation_resource): # expand #attributes into columns to fill in separately gvf = separate_attributes(gvf) @@ -122,7 +124,10 @@ def add_template_annotations(gvf, annotation_file): # change semicolons in function descriptions to colons merged_df['measured_variant_functional_effect_description'] = merged_df[ 'measured_variant_functional_effect_description'].str.replace(';', ':') - + + # add functional_description_resource attribute + merged_df['functional_annotation_resource'] = annotation_resource + # replace NaNs in df with empty string merged_df = merged_df.fillna('') # merge attributes back into a single column @@ -144,7 +149,7 @@ def add_template_annotations(gvf, annotation_file): gvf = gvf[~gvf['#seqid'].astype(str).str.contains("#")] # add functional annotations - template_annotated_gvf = add_template_annotations(gvf, args.functional_annotations) + template_annotated_gvf = add_template_annotations(gvf, args.functional_annotations, args.functional_annotation_resource) # add pragmas to df, then save to .gvf # columns are now 0, 1, ... diff --git a/bin/functions.py b/bin/functions.py index 59dd639b..b82d6eb9 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -12,7 +12,8 @@ vcf_gene=;mutation_type=;viral_lineage=;clade=;multi_aa_name=; \ multiaa_comb_mutation=;alternate_frequency=;measured_variant_functional_effect=;inferred_variant_functional_effect=; \ viral_life_cycle_functional_effect=;URL=; \ - citation=;comb_mutation=;measured_variant_functional_effect_description=;heterozygosity=; \ + citation=;comb_mutation=;measured_variant_functional_effect_description=; \ + mutation_functional_annotation_resource=;functional_annotation_resource=;heterozygosity=; \ clade_defining=;variant=;variant_type=;voi_designation_date=; \ voc_designation_date=;vum_designation_date=;status=;' From b72ebccab3b56750c68c856d7ab01c97ad13eeb8 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 18:54:32 -0700 Subject: [PATCH 075/161] add functional annotation columns as GVF attributes --- bin/addfunctions2gvf.py | 7 ++++++- bin/functions.py | 10 ++++++---- 2 files changed, 12 insertions(+), 5 deletions(-) diff --git a/bin/addfunctions2gvf.py b/bin/addfunctions2gvf.py index 7c1e122c..d7213535 100755 --- a/bin/addfunctions2gvf.py +++ b/bin/addfunctions2gvf.py @@ -47,7 +47,9 @@ def add_template_annotations(gvf, annotation_file, annotation_resource): # drop columns that are going to be re-added in the merge functional_attributes = ["measured_variant_functional_effect", "measured_variant_functional_effect_description", - "URL", "citation"] #"comb_mutation" + "URL", "citation", "organism", "reference_accession", "reference_database_name", 'CVX_code', + 'DrugBank_Accession_Number', 'Antibody_Registry_ID', "author", "publication_year", "DOI", "PMID", "peer_review_status", + "curator", "mutation_functional_annotation_resource"] #"comb_mutation" gvf = gvf.drop(columns=functional_attributes) # load functional annotations spreadsheet @@ -128,6 +130,9 @@ def add_template_annotations(gvf, annotation_file, annotation_resource): # add functional_description_resource attribute merged_df['functional_annotation_resource'] = annotation_resource + # make sure 'publication_year' is an integer + merged_df['publication_year'] = merged_df['publication_year'].str.replace('.0', '', regex=False) + # replace NaNs in df with empty string merged_df = merged_df.fillna('') # merge attributes back into a single column diff --git a/bin/functions.py b/bin/functions.py index b82d6eb9..22d60fa5 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -8,14 +8,16 @@ product=;protein_alias=;protein_name=;protein_symbol=;\ protein_id=;alias_protein_id=;locus_tag=;ps_filter=;ps_exc=; \ mat_pep=;mat_pep_desc=;mat_pep_acc=;ro=;ao=;dp=;sample_size=; \ - Reference_seq=;Variant_seq=;nt_name=;aa_name=;hgvs_nt=;hgvs_aa=;hgvs_alias=; \ + Reference_seq=;Variant_seq=;nt_name=;aa_name=;hgvs_nt=;hgvs_aa=;hgvs_alias=;heterozygosity=; \ vcf_gene=;mutation_type=;viral_lineage=;clade=;multi_aa_name=; \ multiaa_comb_mutation=;alternate_frequency=;measured_variant_functional_effect=;inferred_variant_functional_effect=; \ - viral_life_cycle_functional_effect=;URL=; \ + viral_life_cycle_functional_effect=;author=;publication_year=;DOI=;PMID=;URL=;peer_review_status=; \ citation=;comb_mutation=;measured_variant_functional_effect_description=; \ - mutation_functional_annotation_resource=;functional_annotation_resource=;heterozygosity=; \ + mutation_functional_annotation_resource=;functional_annotation_resource=;curator=; \ clade_defining=;variant=;variant_type=;voi_designation_date=; \ - voc_designation_date=;vum_designation_date=;status=;' + voc_designation_date=;vum_designation_date=;status=; \ + organism=;reference_accession=;reference_database_name=; \ + CVX_code=;DrugBank_Accession_Number=;Antibody_Registry_ID=;' empty_attributes = empty_attributes.replace(" ", "") From ce1370027da50d162b947336ffc9e00af3a9ad9d Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 19:00:30 -0700 Subject: [PATCH 076/161] change 'measured_variant_functional_effect_description' attribute to 'variant_functional_effect_description' --- bin/addfunctions2gvf.py | 8 ++++---- bin/functions.py | 2 +- 2 files changed, 5 insertions(+), 5 deletions(-) diff --git a/bin/addfunctions2gvf.py b/bin/addfunctions2gvf.py index d7213535..d7699bb9 100755 --- a/bin/addfunctions2gvf.py +++ b/bin/addfunctions2gvf.py @@ -8,7 +8,7 @@ This script annotates GVF files with the functional annotation. The attributes completed by this script are: -["measured_variant_functional_effect", "measured_variant_functional_effect_description", "source", +["measured_variant_functional_effect", "variant_functional_effect_description", "source", "citation", "comb_mutation"] """ @@ -46,7 +46,7 @@ def add_template_annotations(gvf, annotation_file, annotation_resource): gvf = separate_attributes(gvf) # drop columns that are going to be re-added in the merge - functional_attributes = ["measured_variant_functional_effect", "measured_variant_functional_effect_description", + functional_attributes = ["measured_variant_functional_effect", "variant_functional_effect_description", "URL", "citation", "organism", "reference_accession", "reference_database_name", 'CVX_code', 'DrugBank_Accession_Number', 'Antibody_Registry_ID', "author", "publication_year", "DOI", "PMID", "peer_review_status", "curator", "mutation_functional_annotation_resource"] #"comb_mutation" @@ -124,8 +124,8 @@ def add_template_annotations(gvf, annotation_file, annotation_resource): 'mutation_group', sort=False).ngroup().astype(str) # change semicolons in function descriptions to colons - merged_df['measured_variant_functional_effect_description'] = merged_df[ - 'measured_variant_functional_effect_description'].str.replace(';', ':') + merged_df['variant_functional_effect_description'] = merged_df[ + 'variant_functional_effect_description'].str.replace(';', ':') # add functional_description_resource attribute merged_df['functional_annotation_resource'] = annotation_resource diff --git a/bin/functions.py b/bin/functions.py index 22d60fa5..f6f2a210 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -12,7 +12,7 @@ vcf_gene=;mutation_type=;viral_lineage=;clade=;multi_aa_name=; \ multiaa_comb_mutation=;alternate_frequency=;measured_variant_functional_effect=;inferred_variant_functional_effect=; \ viral_life_cycle_functional_effect=;author=;publication_year=;DOI=;PMID=;URL=;peer_review_status=; \ - citation=;comb_mutation=;measured_variant_functional_effect_description=; \ + citation=;comb_mutation=;variant_functional_effect_description=; \ mutation_functional_annotation_resource=;functional_annotation_resource=;curator=; \ clade_defining=;variant=;variant_type=;voi_designation_date=; \ voc_designation_date=;vum_designation_date=;status=; \ From 626dae70a10e98bae1cdabbf2f62b7287feaa95d Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 19:24:50 -0700 Subject: [PATCH 077/161] adapt to new DH template format --- bin/convert_pokay_to_virusmvp.py | 22 +++++++++---------- ...splitmutationnames_functionalannotation.py | 9 +++----- 2 files changed, 14 insertions(+), 17 deletions(-) diff --git a/bin/convert_pokay_to_virusmvp.py b/bin/convert_pokay_to_virusmvp.py index 16473a33..1f37d71f 100755 --- a/bin/convert_pokay_to_virusmvp.py +++ b/bin/convert_pokay_to_virusmvp.py @@ -50,16 +50,16 @@ def combination_mutation(c_mutations, c_mutation): def data_cleanup(dframe): - dframe['measured variant functional effect description'] = dframe[ - 'measured variant functional effect description'].apply( + dframe['variant functional effect description'] = dframe[ + 'variant functional effect description'].apply( lambda x: ','.join(map(str, x))) - dframe['measured variant functional effect description'] = dframe[ - 'measured variant functional effect description'].str.replace(',#', '') - dframe['measured variant functional effect description'] = dframe[ - 'measured variant functional effect description'].str.replace('#', '') - dframe['measured variant functional effect description'] = dframe[ - 'measured variant functional effect description'].str.strip() + dframe['variant functional effect description'] = dframe[ + 'variant functional effect description'].str.replace(',#', '') + dframe['variant functional effect description'] = dframe[ + 'variant functional effect description'].str.replace('#', '') + dframe['variant functional effect description'] = dframe[ + 'variant functional effect description'].str.strip() #dframe['comb_mutation'] = dframe['comb_mutation'].apply( # lambda x: x[1:-1]) @@ -149,7 +149,7 @@ def extract_metadata(inp_file, chunk, df): del function[chunk[url[index_url - 1]]] df_func = pd.DataFrame(function.items(), columns=['url', - 'measured variant functional effect description']) + 'variant functional effect description']) df_list = [mutation_name, gene_name, function_category] #, comb_mutation, heterozygosity] @@ -192,14 +192,14 @@ def write_tsv(dframe): dataFrame_cols = ['organism', 'reference accession', 'reference database name', 'nucleotide position', 'original mutation description', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', 'gene name', 'gene symbol', 'gene orientation', 'strand orientation', 'protein name', 'protein symbol', 'measured variant functional effect', 'inferred variant functional effect', 'viral life cycle functional effect', -'measured variant functional effect description', 'CVX code', 'DrugBank Accession Number', 'Antibody Registry ID', 'author', 'publication year', 'URL', 'DOI', 'PMID', +'variant functional effect description', 'CVX code', 'DrugBank Accession Number', 'Antibody Registry ID', 'author', 'publication year', 'URL', 'DOI', 'PMID', 'peer review status', 'curator', 'mutation functional annotation resource'] else: dataFrame_cols = ['organism', 'reference accession', 'reference database name', 'nucleotide position', 'original mutation description', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', 'gene name', 'gene symbol', 'protein name', 'protein symbol', 'measured variant functional effect', 'inferred variant functional effect', 'viral life cycle functional effect', -'measured variant functional effect description', 'CVX code', 'DrugBank Accession Number', 'Antibody Registry ID', 'author', 'publication year', 'URL', 'DOI', 'PMID', +'variant functional effect description', 'CVX code', 'DrugBank Accession Number', 'Antibody Registry ID', 'author', 'publication year', 'URL', 'DOI', 'PMID', 'peer review status', 'curator', 'mutation functional annotation resource'] dataFrame = pd.DataFrame(columns=dataFrame_cols) diff --git a/bin/splitmutationnames_functionalannotation.py b/bin/splitmutationnames_functionalannotation.py index eebcd313..74688633 100755 --- a/bin/splitmutationnames_functionalannotation.py +++ b/bin/splitmutationnames_functionalannotation.py @@ -42,16 +42,13 @@ def parse_args(): args = parse_args() - dataFrame_cols = ['organism', 'reference accession', 'reference database name', 'nucleotide position', -'original mutation description', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias', 'comb_mutation', -'gene name', 'gene symbol', 'protein name', 'protein symbol', 'measured variant functional effect', -'inferred variant functional effect', 'viral life cycle functional effect', 'measured variant functional effect description', -'author', 'publication year', 'URL', 'DOI', 'PMID', 'peer review status', 'curator', 'mutation functional annotation resource'] - # split names in functional annotations file # read in functional annotations file df = pd.read_csv(args.functional_annotations, sep='\t', header=0) + + dataFrame_cols = df.columns.tolist() + ['comb_mutation'] + # remove any leading/trailing spaces for column in df.columns: df[column] = df[column].astype(str).str.strip() From 377ad62ad92253d601da07552ac13af91be95556 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 24 Oct 2024 19:27:15 -0700 Subject: [PATCH 078/161] update column names --- ...kay_functionalAnnotation_SARSCoV2_v3.0.tsv | 3800 ++++++++--------- 1 file changed, 1900 insertions(+), 1900 deletions(-) diff --git a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v3.0.tsv b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v3.0.tsv index ccb13efb..0fa0f393 100644 --- a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v3.0.tsv +++ b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v3.0.tsv @@ -1,1900 +1,1900 @@ -organism reference accession reference database name nucleotide position original mutation description nucleotide mutation amino acid mutation amino acid mutation alias gene name gene symbol protein name protein symbol measured variant functional effect inferred variant functional effect viral life cycle functional effect measured variant functional effect description CVX code DrugBank Accession Number Antibody Registry ID author publication year URL DOI PMID peer review status curator mutation functional annotation resource -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) viral load This mutant causes a 0.41x fold change in the infectious virus production rate. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has a 0.66x fold change in EC50 value with Remdesivir. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has an inhibition rate of virus production by Remdesivir of 0.80. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has a 0.27x fold change in EC50 value with Remdesivir. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has an inhibition rate of virus production by Remdesivir of 0.78. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) viral load This mutant causes a 0.48x fold change in the infectious virus production rate. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.526 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for 6 convalescent sera." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.8x reduction in IC50 serum dilution concentration for 6 convalescent sera." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,22992,23012,23664 L5F,S477N,E484K,A701V NC_045512.2:g.13C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 114 test-positive were Iota. Two dose vaccine efficacy against Iota was 95.7 (81.7-99.0%), one dose VE was 88.8 (0.7-98.7)%. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,25186 L5F,Q1208H NC_045512.2:g.13C>T,NC_045512.2:g.3624G>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Gln1208His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Four of the convalescent sera tested showed 4-fold or greater improvement in neutralization efficiency. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21587 P9S NC_045512.2:g.25C>T YP_009724390.1:p.Pro9Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2M28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21597 S12F NC_045512.2:g.35C>T YP_009724390.1:p.Ser12Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects A variant in low % circulation, predicted to have a similar effect to the experimentally verified S12P, which introduces a new signal peptide, altering cleavage to occur between residues C15 and V16, thereby eliminating the C15-C136 disulfide bond – similarly to escape mutants at positions C15 and C136. This in turn decreases to varying degrees N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600 S13I NC_045512.2:g.38G>T YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The S13I mutation dampened binding of 5 mAbs and abrogated binding of 5 additional mAbs out of 11 neutralizing mAbs evaluated. Predicted to shift the signal peptide cleavage site from S13-Q14 to C15-V16, which can affect NTD conformation. PG: in saying S12F does not shift the signal peptide nor affect mAb binding, this manuscript appears to contradict the text of McCallum et al.'s earlier 2021 manuscript stating that S12F *does* affected some mAb binding via putative signal peptide shift. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018 S13I,W152C NC_045512.2:g.38G>T,NC_045512.2:g.456G>T YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The B.1.427/B.1.429 S13I/W152C NTD did not bind to any NTD-directed neutralizing mAbs, which are known to target a single antigenic site (antigenic site i), whereas binding of the non-neutralizing S2L20 mAb to the NTD antigenic site iv was not affected by any mutants, confirming proper retention of folding. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Antibody neutralization assays showed 6.7-fold resistance against 7/8 convalescent plasma. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Swab samples N/NP viral RNA is approximately 2-fold higher in B.1.427/B.1.429 than in non-variant viruses. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 9 plasma collected 15 to 28 days after early 2020 infections, neutralization reduced 4.9-fold for B.1.427/B.1.429 compared to wildtype (D614G). In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.427/B.1.429 pseudotyped virus, as well as WT and other VOCs. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using HIV pseudotype: Neutralization potency of 11 Moderna mRNA1273-elicited plasma (7-27 days post-2nd dose) was reduced ~2.8-fold compared to wildtype (D614G) S. It was reduced ~4-fold in 14 Pfizer/BioNtech BNT162b2-elicited plasma (7-27 days post-2nd dose). Using VSV pseudotype: we observed a 3-fold average reduction of Pfizer/BioNtech BNT162b2-elicited plasma neutralizing activity. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.249 (1.7-fold). Neutralization against 10 convalescent plasma was somewhat poorer (3.1-fold). Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 14 of 34 RBD-specific mAbs showed reduced neutralization to the B.1.427/B.1.429 variant pseudotype. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility "Lineages bearing these spike mutations comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the ""California"" or ""West Coast"" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI:1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020." Peng 2021 https://doi.org/10.1093/cid/ciab283 doi:10.1093/cid/ciab283 33788923 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.427/429 reduced 2.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 6 of 11 (55%) vaccine recipients (Moderna or Pfizer), showed 2x reduction in neutralization to a B.1.429 lineage virus. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 2.7x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 2.3x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403,25135 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G,K1191N NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3573G>T YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys1191Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for CAL.20C (B.1.429), and a slight decrease in CD8+ percentage (p=0.0201) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21604,21604 Q14H,Q14H NC_045512.2:g.42G>C,NC_045512.2:g.42G>T YP_009724390.1:p.Gln14His,YP_009724390.1:p.Gln14His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21605 C15R NC_045512.2:g.43T>C YP_009724390.1:p.Cys15Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21606 C15F NC_045512.2:g.44G>T YP_009724390.1:p.Cys15Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates neutralization by N-terminal-domain-targeting mAbs 4-19. Impairs neutralization by N-terminal-domain-targeting mAbs 4A8 and 2-17. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggetsing that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 34931886 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132 L18F,T20N,P26S,D138Y,R190S NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "The neutralization titer of NTD-binding mAb159 was 133-fold reduced on P.1 compared to Victoria (~wild type), with only 64% neutralization at 10 μg/mL. Residues 20, 18, and 138 form a cluster underlying the 245–259 loop, which inserts into a groove between the light and heavy chains of Fab 159. In addition, the N-terminal residues preceding residue 18 interact with the antibody and may be perturbed. Given that there is likely a single supersite (""i"") for potent NTD-binding antibodies, the binding of many of these are likely affected. Using 20 potent (primaruly anti-RBD) antibodies, neutralization was measured by a focus reduction neutralization test (FRNT) and compared with neutralization of Victoria (~wild type) and variants B.1.1.7 and B.1.351. Compared to Victoria neutralization by the mAbs was significantly impacted by P.1, with 12/20 showing > 10-fold reduction in FRNT50 titer and a number showing complete knockout of activity. The results with P.1 showed a greater impact compared to B.1.1.7 but were, as expected, similar to those with B.1.351." Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Amongst RBD-targeting Emergency Use Authorized monoclonal antibody treatments CB6, LY-CoV555 and REGN10933 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1, but REGN10987 activity remains strong. RBD-targeting monoclonal antibodies 2-15 and C121 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. N terminal domain targeting monoclonal antibodies 5-7, 4-8, 4-18 and 2-17 have abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 33688656 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 12 Moderna vaccinee sera 15 days post second dose (43 days since first vaccination), an average 2.8x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 4.8x decrease against the full P.1 type vs WA-1 was observed, though overall with a higher ID50 reciprocal value. In 10 Pfizer vaccinee sera 7 days or more post second dose (28 days or more since first vaccination), an average 2.2x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.8x decrease against the full P.1 type vs WA-1 was observed, with similar variant ID50 reciprocal value. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 33688656 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure CryoEM reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the “up” position. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 33688656 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In convalescent sera one month or more post-infection in Spring 2020, an average 6.5x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.4x decrease against the full P.1 type vs WA-1 was observed, with better full P.1 ID50 reciprocal value compared to the 10-mutation model. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 33688656 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection After a 128 day interval, a patient in Sao Paulo State, Brazil reinfected with P.1 (first episode likely predates P.1 emergence). Both cases were fairly mild (difficulty breathing, tiredness, dizziness and fatigue). Malta Romano 2021 https://doi.org/10.1590/S1678-9946202163036 doi:10.1590/S1678-9946202163036 33909850 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Gamma (P.1) variant is 0.6x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 3.0x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 4.1x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 349 test-positive were Gamma. Two dose vaccine efficacy against Gamma was 95.5 (90.9-97.8%), one dose VE was 74.2 (43.8-88.1%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Three healthcare workers (29-50yo) had confirmed P.1 [Gamma] re-infection in the Amazonas region of Brazil 3-9 months after initial infection from viruses with distinct lineage from P.1, but mild symptoms upon re-infection and evidence for infectiousness during re-infection. Naveca 2021 https://doi.org/10.21203/rs.3.rs-318392/v1 doi:10.21203/rs.3.rs-318392/v1 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~6x cleavage of S2 relative to WA1 (D614G) wildtype by Gamma variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but H655Y is upstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was slightly lower against B.1.1.248 variant constellation in sera tested from most of the 15 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped P.1 virus has reduced neutralization activity vs wild type: 6.7x (30 sera Pfizer median 9 days post 2nd dose) and 4.5x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Unlike wild type or B.1.1.7, P.1 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. Montagutelli 2021 https://doi.org/10.1101/2021.03.18.436013 doi:10.1101/2021.03.18.436013 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.248 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07. B.1.1.248 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.7 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0039 for mild resistance. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.248 variant constellation in 10 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples, P=0.0020. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 16.6% in this B.1.1.248 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 33972942 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed. Andrade 2021 https://doi.org/10.1101/2021.04.14.439719 doi:10.1101/2021.04.14.439719 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed. Andrade 2021 https://doi.org/10.1101/2021.04.14.439719 doi:10.1101/2021.04.14.439719 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Among 46,884 HCWs in Manaus, Brazil vaccinated with at least one dose of CoronaVac, a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%; 95% CI, 11.3 - 71.4) in the odds of symptomatic SARS-CoV-2 infection was observed during the period 14 days or more after receiving the first dose. Estimated vaccine effectiveness of at least one dose against any SARS-CoV-2 infection was 35.1% (95% CI, −6.6 - 60.5) in the same time period. Hitchlings 2021 https://doi.org/10.1101/2021.04.07.21255081 doi:10.1101/2021.04.07.21255081 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.15x *increase* in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Neutralizing antibodies that were generated following a mild infection with SARS-CoV-2 B.1.128 were effective in vitro, and likely protective, against the SARS-CoV-2 P.1. variant in the majority of individuals based on 60 convalescent sera tested. Mendes-Correa 2021 https://doi.org/10.1101/2021.05.11.21256908 doi:10.1101/2021.05.11.21256908 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding VSV pseudotype P.1 showed 4.8-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections). Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking VSV pseudotype P.1 showed slight decrease in cell entry relative to wild type in 262T and 263T-ACE2 (kidney) cell lines. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness VSV pseudotype P.1 entry mediated by the S proteins of the P.1 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Cell fusion proficiency was slight impaired. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for P.1 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the P.1 variants used, using the most popular as a stand in] McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against P.1 at various time points using pseudovirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 85%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 256 for B.1.1.7 virus. Compare to somewhat stronger neutralization titer for wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion PBMCs of 11 mild COVID-19 patients collected 38-80 days after symptom onset were stimulated with the 15-mer peptide pools (w/ 10 residue overlaps) from the wholle viral proteome, showing no significant CD4+ cell count effect for P.1, and a slight increase in CD8+ percentage (p=0.0195) by Activation Induced Marker (AIM) assay (cellular immunity measurement). [in the text, this increase is not noted as signficant, even though p=0.05 is used elsewhere in the text as a signficance threshold] Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness P.1 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with Lilly mAb combination LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of P.1. There was also escape from neutralization of P.1 by REGN10933 (one of 2 in Regeneron's mAb cocktail) and a modest reduction in neutralization of P.1 by AstraZeneca's AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized P.1 with all reaching a plateau at 100% neutralization; interestingly, ADG30 showed a slight increase of neutralization of P.1. S309 Vir was largely unaffected, although for several viruses, including P.1, the antibody failed to completely neutralize, conceivably reflecting incomplete glycosylation at N343, since the sugar interaction is key to binding of this antibody. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The relative transmissibility of P.1 estimated at the national level (Italy) varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. PG: variant list has been abbreviated due to mixed K417 bases in this lineage, potential miscalls of deletions Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21801,22206,22334,22600,22600,22810,22811,22812,22813,22813,22879,22881,22882,22882,22986,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D80A,D215G,W258R,R346S,R346S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,A475V,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.772T>C,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1424C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ala475Val,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments and mutations from variants of concern completely ablates neutralization in 19 of 21 convalescents plasma collected mean 1.3 months post infection. [actual Y145del from manuscript substituted with more common Y144del description] Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801 L18F,D80A NC_045512.2:g.52C>T,NC_045512.2:g.239A>C YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The L18F and D80A of the B.1.351 lineage lead to reconfiguration of the N-terminal segment despite the disulfide between Cys16 and Cys136 that partly anchors the N-terminal peptide. The most consequential changes are probably from the triple residue deletion... which causes a shift of the nearby loop 144-155 and must also reconfigure the adjacent disorder loop (residues 246-260), both of which form part of the neutralizing epitopes...bringing large changes in the antigenic surface in this region. Cai 2021 https://doi.org/10.1101/2021.04.13.439709 doi:10.1101/2021.04.13.439709 33880477 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The 501Y.V2 to first wave IC50 ratio ranged from 6 to 200-fold. Averaging across all 7 participant convalescent sera highlighted the dramatic decrease in sensitivity to neutralization of authentic 501Y.V2 variants. PG: I'm purposefully ignoring D614G and A701V as contributors Cele 2021 https://doi.org/10.1038/s41586-021-03471-w doi:10.1038/s41586-021-03471-w 33780970 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In human sera 8 weeks post-vaccination with INO-4800, a ~7-fold reduction in B.1.351 neutralization was observed. Andrade 2021 https://doi.org/10.1101/2021.04.14.439719 doi:10.1101/2021.04.14.439719 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike). Riddell 2021 https://doi.org/10.1101/2021.04.17.440246 doi:10.1101/2021.04.17.440246 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike). Riddell 2021 https://doi.org/10.1101/2021.04.17.440246 doi:10.1101/2021.04.17.440246 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pzifer vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1), but were all infected before 14 days post second vaccination. Kustin 2021 https://doi.org/10.1101/2021.04.06.21254882 doi:10.1101/2021.04.06.21254882 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Wu 2021 https://doi.org/10.1101/2021.04.13.439482 doi:10.1101/2021.04.13.439482 33880468 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Wu 2021 https://doi.org/10.1101/2021.04.13.439482 doi:10.1101/2021.04.13.439482 33880468 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Wu 2021 https://doi.org/10.1101/2021.04.13.439482 doi:10.1101/2021.04.13.439482 33880468 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals (5/9) and recipients of a only a single dose of mRNA vaccine (10/11) – heterotypic neutralization dropped to negligible levels, particularly against B.1.351. Skelly 2021 https://doi.org/10.21203/rs.3.rs-226857/v1 doi:10.21203/rs.3.rs-226857/v1 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR22 molecule had a 1.57x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness B.1.351 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of B.1.351. There was also escape from neutralization of B.1.351 by REGN10933 and a modest reduction in neutralization of B.1.351 by AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized B.1.351. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.054x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 8 for B.1.351 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Sera from individuals who have been infected with Delta does not have strong neutralising activity against Beta. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Beta neutralizing antibodies is 0.803x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.351. We observed an increase (relative to D614G) in binding of soluble ACE2 to B.1.351, and to a much gearter extent to B.1.1.7, which both carry the N501Y mutation (see Fig 3). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Pseudotype lentivirus for the full B.1.351 Spike variant list shows increase affinity for ACE2 as measured by IC50. This is in contrast to B.1.1.7 which showed no major change, indicating that the shared N501Y mutation is the driver of affinity change, attentuated in the B.1.1.7 mutatioon set, but maintained in the B.1.351 lineage. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 6.3x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Beta Variant B.1.351 RBD significantly better than w.t. SARS-CoV-2 RBD. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.07x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed for B.1.351 a CD4+ cell count decrease (29%, p=0.00063) as well as CD8+ (33%, p=0.0016) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera). Madhi 2021 https://doi.org/10.1056/NEJMoa2102214 doi:10.1056/NEJMoa2102214 33725432 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against Beta. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Encouragingly, we find that the majority of T cell responses in recipients of two doses of the BNT162b2 vaccine are generated by epitopes that are invariant between the [wildtype] and two of the current variants of concern (B.1.1.7 and B.1.351). In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals and recipients of a only a single dose of mRNA vaccine – heterotypic neutralization dropped to negligible levels, particularly against B.1.351. Skelly 2021 https://doi.org/10.21203/rs.3.rs-226857/v1 doi:10.21203/rs.3.rs-226857/v1 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 8.2x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The neutralizing activity of 16/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.351, with similar results for the live virus. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Beta neutralizing antibodies is 0.899x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.351 v2 virus has reduced neutralization activity vs wild type: 41.2x (30 sera Pfizer median 9 days post 2nd dose) and 20.8x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021 https://doi.org/10.1056/NEJMoa2103055 doi:10.1056/NEJMoa2103055 33951374 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v2 reduced 7.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type). Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021 https://doi.org/10.1056/NEJMoa2103055 doi:10.1056/NEJMoa2103055 33951374 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing] Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing] Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera). Madhi 2021 https://doi.org/10.1056/NEJMoa2102214 doi:10.1056/NEJMoa2102214 33725432 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.351 sample. Contrast this with 1.4-fold reduction for just the pseudovirus combination of ""key"" B.1.351 mutations K417N+E484K+N501Y. WA1 and B.1.351 FRNT50 titers correlated weakly at the individual level, with some individual’s serum potently neutralizing WA1 while having FRNT50 for B.1.351 below the assay limit of detection (1:20)." Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 33851185 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing] Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.351 pseudotyped virus model ablates neutralization by RBD-directed mAbs CB6, 4-20, 2-4, 2-43, 910-30, 2-302-15, LY-Cov555, C121. B.1.351 pseudotyped virus model severely impairs neutralization by RBD-directed mAb 1-20. B.1.351 pseudotyped virus model impairs neutralization by RBD-directed mAb REGN10933. B.1.351 pseudotyped virus model ablates neutralization by N-terminal-domain-directed mAbs 5-24, 4-8, 4A8, 4-19. B.1.351 pseudotyped virus model severely impairs neutralization by N-terminal-domain-directed mAb 2-17. B.1.351 pseudotyped virus model impairs neutralization by N-terminal-domain-directed mAb 5-7. PG: Live virus data for the same mAbs is similar, but 1-20 becomes severally impaired, REGN10933 activity is ablated, and Brii-196 becomes impaired. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type). Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 3.2x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type). Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy [Contrary to how this paper has been cited, Voysey et al. do NOT show evidence of decreased effectiveness of ChAdOx1 (AstraZeneca) against the South African B.1.351 lineage. Insufficient numbers reaching the primary study endpoint were available in that arm of the vaccine study to report any statistics from the South African participants. Additionally, the study period of the paper ended in November 2020, while the earliest reported case of this lineage is October (covariants.org), only becoming dominant by mid-November.] Voysey 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021 https://doi.org/10.1056/NEJMoa2103055 doi:10.1056/NEJMoa2103055 33951374 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021 https://doi.org/10.1056/NEJMoa2103055 doi:10.1056/NEJMoa2103055 33951374 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms had mean ~6x reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: while B.1.1.7 and D614G showed neutralization by nasal swab from only one different previously infected vacinee neutralizing at weeks 3 and 6, B.1.351 showed zero neutralization at either time point in any sample (and relatively impaired serum neutralization). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape A 1.8-fold drop in FRNT50 for B.1.351 was observed in 44 sera collected between 1 and 301 post-infection. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 33851185 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR16m molecule had a 0.036x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR16m molecule had a 99.7x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR16m molecule had a 6.7x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with all key mutations from B.1.351 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting some synergy between the mutations to decrease cell entry fitness (i.e. cell entry is liklely not the driver of this lineage's dominance). Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,23060,23061,23062,23063,22810,22811,22812,22813,22813,23012,23399,23401,23402,23403 L18F,D80A,D215G,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The most significant loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against authentic B.1.351 lineage virus (9.2-fold). Neutralization against 10 convalescent plasma was poorer (18.7x). Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks. Meister 2021 https://doi.org/10.1093/infdis/jiab260 doi:10.1093/infdis/jiab260 33993274 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication] Ribas Freitas 2021 https://doi.org/10.1101/2021.04.13.21255281 doi:10.1101/2021.04.13.21255281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the Parana state of Brazil, patients aged 20-29 years experienced a tripling of their case fatality rate (CFR), from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling comparing February to January in 2021. Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil. [this is somewhat indirect evidence that assume greatly increasing proportion of P.1 cases in March (70%) compared to February, but the first official ID of P.1 in Parana state (Feb 16th) may be due to testing procedures rather than actual prevalence] Santos de Oliviera 2021 https://doi.org/10.1101/2021.03.24.21254046 doi:10.1101/2021.03.24.21254046 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication] Ribas Freitas 2021 https://doi.org/10.1101/2021.04.13.21255281 doi:10.1101/2021.04.13.21255281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication] Ribas Freitas 2021 https://doi.org/10.1101/2021.04.13.21255281 doi:10.1101/2021.04.13.21255281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22915,22916,22917,23060,23061,23062,23063,23521,23522,23524,23525 L18F,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 (Pfizer) vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains. Mallm 2021 https://doi.org/10.1101/2021.04.27.21254849 doi:10.1101/2021.04.27.21254849 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1, Delta (B.1.617.2) shows mean 2.1x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Relative to B.1, Delta (B.1.617.2) shows 3.64x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,22915,22916,22917,23012,23399,23401,23402,23403 T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this lineage defining mutation combination from B.1.617.3 increased syncytium formation ~2.3x. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,22915,22916,22917,23012,23399,23401,23402,23403 T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this lineage defining mutation combination from B.1.617.3 conferred a ~11.8x drop in neutralization (NT50) [suggesting role for T19R and T95I in half the sera]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,22915,22916,22917,23012,23399,23401,23402,23403 T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this lineage defining mutation combination from B.1.617.3 conferred a ~4.5x infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,23399,23401,23402,23403 T19R,T95I,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22028,22915,22916,22917,23604,23399,23401,23402,23403,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,E156del,L452R,L452R,L452R,P681R,D614G,D614G,D614G,D614G,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.467_472del,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4.5x cleavage of S2 relative to WA1 (D614G) wildtype by Delta (B.1.617.2) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~3.5x for closely related Kappa B.1.617.1 also with P681R at the cleavage site). Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. [Mutation list in publication appears to contain a typo with R158del instead of R158G]" Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 4.0x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Modelling the Delta variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increased 11x relative to wild type (15.3 vs 1.4). [del ~157 truncated due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a coinfection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant. Liu 2021 https://doi.org/10.1101/2021.08.12.456173v3 doi:10.1101/2021.08.12.456173v3 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 2.6x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.020x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.10x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In primary human airway epithelial cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 1.9x relative to wild type (2.7 vs 1.4). This is the Delta variant with the P681R furin cleavage site mutation absent. [del ~157 truncated due to ambiguity] Liu 2021 https://doi.org/10.1101/2021.08.12.456173v3 doi:10.1101/2021.08.12.456173v3 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Plasma neutralizing activity was also assessed against SARS-CoV-2 Delta, Omicron BA.1, BA.2 and BA.4/5 variants using viruses pseudotyped with appropriate variant spikeproteins. Delta breakthrough infection resulted in 15-fold increased neutralizing titers. Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Plasma neutralizing activity in 49 participants was measured using HIV-1 pseudotyped with the 100 WT SARS-CoV-2 spike protein. Delta breakthrough infection resulted in 11-fold increased geometric mean half-maximal neutralizing titer (NT50). Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Delta neutralizing antibodies is 0.872x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Delta Variant B.1.617.2 RBD or w.t. SARS-CoV-2 RBD with nearly equal potency determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 507 pM for binding to the Delta B.1.617.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Delta neutralizing antibodies is 0.952x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy The incidence rate of Covid-19 during the Delta-dominant period (Jul-Aug 2021) was lower for late vaccinated (49.0/1000 person-years) [formerly placebo] versus early vaccinated (77.1/1000 person-years) participants in the Moderna mRNA-1273 Phase 3 trials, representing a 36.4% VE reduction (95% CI 17.1%-51.5%). There were fewer severe Covid-19 cases in the late group (6; 6.2/1000 person-years) than early (13; 3.3/1000 person-years), representing a 46.0% reduction (95% CI −52.4%-83.2%). Three Covid-19 related hospitalizations occurred with two resulting deaths in the early group. Baden 2021 https://doi.org/10.1101/2021.09.17.21263624 doi:10.1101/2021.09.17.21263624 34611666 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 34437521 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021 https://doi.org/10.15585/mmwr.mm7034e3 doi:10.15585/mmwr.mm7034e3 34437519 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.92x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Delta Molnupiravir (MK-4482) had ~4x fold drop. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 35579953 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role. Tang 2021 https://doi.org/10.1101/2021.08.11.21261885 doi:10.1101/2021.08.11.21261885 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). Chia 2021 https://doi.org/10.1101/2021.07.28.21261295 doi:10.1101/2021.07.28.21261295 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 34437521 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021 https://doi.org/10.15585/mmwr.mm7034e3 doi:10.15585/mmwr.mm7034e3 34437519 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role. Tang 2021 https://doi.org/10.1101/2021.08.11.21261885 doi:10.1101/2021.08.11.21261885 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021 https://doi.org/10.15585/mmwr.mm7034e3 doi:10.15585/mmwr.mm7034e3 34437519 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 34437521 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 34437521 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021 https://doi.org/10.15585/mmwr.mm7034e3 doi:10.15585/mmwr.mm7034e3 34437519 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role. Tang 2021 https://doi.org/10.1101/2021.08.11.21261885 doi:10.1101/2021.08.11.21261885 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). Chia 2021 https://doi.org/10.1101/2021.07.28.21261295 doi:10.1101/2021.07.28.21261295 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021 https://doi.org/10.15585/mmwr.mm7034e3 doi:10.15585/mmwr.mm7034e3 34437519 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 34437521 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 34437521 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death. 2021 https://doi.org/10.1503/cmaj.211248 doi:10.1503/cmaj.211248 34610919 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance. Twohig 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death. 2021 https://doi.org/10.1503/cmaj.211248 doi:10.1503/cmaj.211248 34610919 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance. Twohig 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death. 2021 https://doi.org/10.1503/cmaj.211248 doi:10.1503/cmaj.211248 34610919 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccination of health care workers in Delhi was started in early 2021, with the ChdOx-1 (Astra Zeneca) vaccine. Surveillance has suggested B.1.1.7 dominance in the Delhi area during early 2021, with growth of B.1.617 since March 2021. During the wave of infections during March and April an outbreak of SARS-CoV-2 was confirmed in 33 vaccinated staff members at a single tertiary centre (age 27-77 years). Sequencing revealed that 16/33 were B.1.617.2, with a range of other B lineage viruses including B.1.1.7 for the rest except one A lineage case. Importantly no severe cases were documented in this event. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Case 62541 cluster in Singapore included a fully vaccinated nurse 2 months post-vaccine [likely Pfizer based on dates and supply], and a doctor of unknown vaccine status. This cluster was caused by a B.1.617.2 virus [via crossreference to Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Denmark, for the period Jan 1 to Jun 27, 2021, Delta variant was associated with increased an risk ratio of 2.83 [95% CI 2.02–3.98] for hospitalization. Bager 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.2 aka Delta) showed a 2.34x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.89x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Delta (B.1.617.2) has an IC50 fold change of 46.5x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Delta (B.1.617.2) variant is 0.6x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Delta (B.1.617.2) has an IC50 fold change of 0.57x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Delta (B.1.617.2) has an IC50 fold change of 0.87x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Delta (B.1.617.2) has an IC50 fold change of 0.15x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,23399,23401,23402,23403 T19R,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21627 T22I NC_045512.2:g.65C>T YP_009724390.1:p.Thr22Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain, frequently observed in various human infection lineages, reduces the tropism of SARS-CoV-2 in F81 (cat kidney, Felis catus) and BHK-21 (golden hamster kidney, Mesocricetus auratus) cell line cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21648 T29I NC_045512.2:g.86C>T YP_009724390.1:p.Thr29Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21717,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23399,23401,23402,23403,23593,23593,24224 Q52R,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,D614G,D614G,D614G,D614G,Q677H,Q677H,F888L NC_045512.2:g.155A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.525 reduced 4.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21717,23012,23593,23593,24224 Q52R,E484K,Q677H,Q677H,F888L NC_045512.2:g.155A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The B.1.525 appears to have poor transmissibility when in competition with B.1.1.7 and other circulating strains in Denmark (early 2021). Albertsen 2021 https://www.covid19genomics.dk/2021-05-08_data-overview.html#b1525 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21752,21752 W64R,W64R NC_045512.2:g.190T>A,NC_045512.2:g.190T>C YP_009724390.1:p.Trp64Arg,YP_009724390.1:p.Trp64Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21759 H66R NC_045512.2:g.197A>G YP_009724390.1:p.His66Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent, especially on a D614 wildtype background. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Neutralization activity of almost all Moderna Phase 1 sera tested actually *increased*. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This deletion outside the receptor binding domain in pseudotyped VSV promoted the capacity of pseudotyped VSV to transduce black flying fox (Pteropus alecto) kidney PabKi.1 cells (17.8%) to a level twice that of human epithelial-like Huh-7 cells (9.8%) Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduces neutralization by structurally unmapped mAb COVA1-21 (cluster XI). Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization activity of almost all convalescent sera tested decreased ~2x. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence The delH69/V70 enhances viral infectivity, indicating its effect on virus fitness is independent to the N501Y RBM change [with which it is found in lineage B.1.1.7] Possibly arisen as a result of the virus evolving from immune selection pressure in infected individuals and possibly only one chronic infection in the case of lineage B.1.1.7. Kemp 2020 https://doi.org/10.1101/2020.12.14.422555 doi:10.1101/2020.12.14.422555 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding No notable change in neutralization efficiency, despite N439K by itself showing a ~2x decrease on average in 16 health workers' convalescent sera. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization activity of convalescent sera tested decreased ~2x with this B.1.1.7 pseudotyped virus. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron (a.k.a. B.1.1.529) Spike pseudotyped VSV and Vero E6 cells has somewhat reduced neutralization (2.7x) vs wild type with monoclonal antibody Sotrovimab (a.k.a. VIR-7831). [delins at 214 omitted for syntax compatibility] Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron breakthrough infection after 3-dose vaccination resulted in a further 3.5-fold and 2.9-fold increase of Omicron BA.1 and BA.2 neutralizing titers. Omicron BA.4/5 showed the highest neutralization resistance of all variants tested, resulting in low geometric mean neutralizing titers in plasma samples obtained after the second vaccine dose (NT50=72). Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron B.1.1.529 (BA.1) neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron (B.1.1.529 [BA.1]) have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Omicron variant and was used to determine neutralizing antibodytitres. There was a 114.84x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 6.61x fold increase in antibody response pre-reinfection. There was a 1194.9x fold increase in antibody response during reinfection. Shete 2022 https://doi.org/10.1101/2022.05.12.491584 doi:10.1101/2022.05.12.491584 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Omicron BA.1 variant is 1.0x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.1 has an IC50 fold change of 0.30x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 73 pM for binding to the Omicron B.1.1.529. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigms’ ACE-2 variant LVE/STR chimera binds to SARS-2 Omicron variant B.1.1.529 spike protein trimer with high affinity. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Omicron BA.1 has an IC50 fold change of 1.26x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Delta variant and was used to determine neutralizing antibodytitres. There was a 24.63x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 4.21x fold increase in antibody response pre-reinfection. There was a 39.27x fold increase in antibody response during reinfection. Shete 2022 https://doi.org/10.1101/2022.05.12.491584 doi:10.1101/2022.05.12.491584 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.1 has an IC50 fold change of 0.08x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Omicron BA.1 has an IC50 fold change of 0.38x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding All 10 individuals with 3 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 3319 NT50. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 35581351 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding All 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 729 NT50. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 35581351 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against B.1 variant and was used to determine neutralizing antibodytitres. There was a 6.76x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 2.06x fold increase in antibody response pre-reinfection. There was a 8.18x fold increase in antibody response during reinfection. Shete 2022 https://doi.org/10.1101/2022.05.12.491584 doi:10.1101/2022.05.12.491584 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.3 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.3 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was somewhat lower against B.1.1.7 in sera tested from most of the 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.7 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2489. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.1.7 sample. Contrast this with 1.3-fold reduction for just the pseudovirus combination of ""key"" B.1.1.7 mutation N501Y." Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 33851185 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild to modest decrease in infection rate amongst the cells, suggesting a net mild negative effect on human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing moderate decrease in infection rate amongst the cells, significantly lower than the deletion or Y453F alone, or their combination, suggesting a synergistic effect on poorer human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, much closer to D614G activity level than Y453F alone, suggesting compensatory effects between the deletion and the mutation in human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,23399,23401,23402,23403,25249,25249,25249 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,D614G,D614G,D614G,D614G,M1229I,M1229I,M1229I NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.298 virus has reduced neutralization activity vs wild type: 1.4x (30 sera Pfizer median 9 days post 2nd dose) and 1.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,25249,25249,25249 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells, markedly higher infectivity than either mutation alone, suggesting a synergistic net neutral effect on human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,25249,25249,25249 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Lentiviral pseudotyped with the key mutations from Mink Cluster 5 was neutralized more easily than D614G in 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,25249,25249,25249 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with all key mutations from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (~50%) decrease in infection rate amongst the cells, suggesting that this anthropozoonotic event is driven by other factors at the expense of human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.7+E484K reduced 2.8x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Compare with 1.2x reduction for B.1.1.7 without E484K. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization capacity GMT of 27 subjects' sera post-infection was markedly worse against B.1.1.7 + E484K than the lineage alone, with a 11.4x drop. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This mutation combination causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x). PG: these effects are laregly missing in the deletion-alone data Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." van Loon 2021 https://doi.org/10.1101/2021.04.15.21255389 doi:10.1101/2021.04.15.21255389 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." van Loon 2021 https://doi.org/10.1101/2021.04.15.21255389 doi:10.1101/2021.04.15.21255389 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence A higher proportion of cases infected with the B.1.1.7 variant were hypoxic on admission compared to other variants (70.0% vs 62.5%, p=0.029), in London between March 13th 2020 and February 17th 2021 (400 B.1.1.7 cases out of 1470 total sequenced). Snell 2021 https://doi.org/10.1101/2021.03.16.21253377 doi:10.1101/2021.03.16.21253377 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, moreso than this combination with the addition of P681H. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021 https://doi.org/10.1136/bmj.n1088 doi:10.1136/bmj.n1088 33985964 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) clinical indicators After adjusting for the age factor, in a prospective Chinese cohort study B.1.1.7 variant infection (compared to B.1.140) was the risk factor for C-reactive protein (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), Serum amyloid A (0.011, 5.031, [1.459, 17.354]), Creatine Kinase (0.034, 4.34, [0.05, 0.91]), CD4+ T lymphocyte (0.029, 3.31, [1.13, 9.71]), and Ground Glass Opacity (0.005, 5.418, [1.656, 17.729]) Song 2021 https://doi.org/10.1101/2021.05.04.21256655 doi:10.1101/2021.05.04.21256655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021 https://doi.org/10.1016/j.cmi.2021.05.007 doi:10.1016/j.cmi.2021.05.007 33984489 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021 https://doi.org/10.1136/bmj.n1088 doi:10.1136/bmj.n1088 33985964 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021 https://doi.org/10.1136/bmj.n1088 doi:10.1136/bmj.n1088 33985964 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021 https://doi.org/10.1016/j.cmi.2021.05.007 doi:10.1016/j.cmi.2021.05.007 33984489 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021 https://doi.org/10.1016/j.cmi.2021.05.007 doi:10.1016/j.cmi.2021.05.007 33984489 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021 https://doi.org/10.1136/bmj.n1088 doi:10.1136/bmj.n1088 33985964 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion). Marquez 2021 https://doi.org/10.1017/ice.2021.195 doi:10.1017/ice.2021.195 33934744 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Second infection in December 2020 with B.1.1.7 after April 2020 initial infection with B.2 in a 78-year-old man with a history of Type 2 diabetes mellitus, diabetic nephropathy on hemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnea, ischemic heart disease, with no history of immunosuppression. Harrington 2021 https://doi.org/10.1093/cid/ciab014 doi:10.1093/cid/ciab014 33421056 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM for binding to the Alpha B1.1.7. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Lessens the potency of mAbs COVA2-17 (~5x, similar to N501Y alone), COVA1-12 (~11x) and COVA1-21 (>100x), which do not compete allosterically." Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 1.7x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.7 pseudotyped virus model impairs binding by RBD-directed mAb 910-30. B.1.1.7 pseudotyped virus model abolishes N-terminal-domain-directed mAbs 5-24, 4-8, and 4A8. B.1.1.7 pseudotyped virus model impairs binding by N-terminal-domain-directed mAbs 2-17, 4-19, 5-7. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020. Possible reinfections were identified in 249 (0.7% [95% CI 0.6-0.8]) of 36509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Graham 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects ~20x resistence to mAb CQ038 by B.1.1.7 pseudotyped virus Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Alpha Variant B.1.1.7 RBD significantly better than GenScript IgG FL18-740 w.t. ACE-2 mAB. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.1.7. We observed a dramatic increase (relative to D614G) in binding of soluble ACE2 to B.1.1.7, and to a lesser extent to B.1.351, which both carry the N501Y mutation (see Fig 3). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion). Marquez 2021 https://doi.org/10.1017/ice.2021.195 doi:10.1017/ice.2021.195 33934744 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 34401884 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 33822770 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 33772577 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 33688655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%). Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 34289274 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) aerosolization Alpha variant cases in a large campus study showed fine-aerosol shedding amongst unmasked participants remained significantly greater for alpha variant infections (18-fold, 95% CI, 3.4 to 92-fold) after adjusting for the increased viral RNA in MTS and saliva, the number of coughs during sampling sessions, and symptom. After controlling for the effect of masks and numbers of coughs during sampling, alpha variant infection was associated with a 100-fold (95% CI, 16 to 650-fold) increase in coarse- and a 73-fold (95% CI, 15 to 350-fold) increase in fine-aerosol RNA shedding. Adenaiye 2021 https://doi.org/10.1093/cid/ciab797 doi:10.1093/cid/ciab797 34519774 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~2.5x cleavage of S2 relative to WA1 (D614G) wildtype by Alpha variant variant as measured by mass spectrometry of Vero-TMPRSS culture. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events First documented cases of domestic cat and dog infections with the B.1.1.7 strain. Hamer 2021 https://doi.org/10.1111/tbed.14122 doi:10.1111/tbed.14122 33955193 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 2.6x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the 47D10. Alpha (B.1.1.7) has an IC50 fold change of 0.40x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks. Meister 2021 https://doi.org/10.1093/infdis/jiab260 doi:10.1093/infdis/jiab260 33993274 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively. Schuit 2021 https://doi.org/10.1093/infdis/jiab171 doi:10.1093/infdis/jiab171 33822064 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively. Schuit 2021 https://doi.org/10.1093/infdis/jiab171 doi:10.1093/infdis/jiab171 33822064 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.44x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure CryoEM analysis of B.1.1.7 demonstrates an increased propensity for 'up', receptor accessible conformation of the Spike protein trimer. Cai 2021 https://doi.org/10.1101/2021.04.13.439709 doi:10.1101/2021.04.13.439709 33880477 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralizing antibody titers of 2/20 (10%) samples showed >10x reduction (sera collected ~1mo post Jan 2020 first wave in China). Neutralizing antibody titers of 8/20 samples (40%) decreased below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China). Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The sera of 16 individuals with time course collection was evaulated against VSV pseudotypes: neutralized D614G at week 2, whereas B.1.1.7 started to be neutralized at week 3, although less efficiently than D614G. B.1.1.7 and D614G strains were similarly neutralized at week 4 (1 week after booster dose). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021 https://doi.org/10.1136/bmj.n1088 doi:10.1136/bmj.n1088 33985964 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 33972942 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We observed a sharp decline in cases when ∼50% of the elderly population was 2 weeks beyond their first vaccination dose and at a time point during which the B.1.1.7 variant gained transmission dominance. In support of this finding, it was suggested that, after the first vaccination dose, more than 70% of patients develop neutralization antibodies,15 and the vaccine efficiency can reach 85%. Munitz 2021 https://doi.org/10.1016/j.xcrm.2021.100264 doi:10.1016/j.xcrm.2021.100264 33899031 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 33972942 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Live virus was tested ex vivo in reconstituted brochial epithelium, and out competed wild type. Touret 2021 https://doi.org/10.1101/2021.03.22.436427 doi:10.1101/2021.03.22.436427 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.39x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization assays of B.1.1.7 virus showed a reduction of 2.5-fold (14 days post 2nd dose AstraZeneca, n=15), 2.1-fold (28 days post 2nd dose AstraZeneca, n=10), and 3.3-fold (7-17 days post 2nd dose Pfizer-BioNTech, n=25). [D1119H was included in the original paper, assumed typographical error and changed to D1118H] Supasa 2021 https://doi.org/10.1016/j.cell.2021.02.033 doi:10.1016/j.cell.2021.02.033 33743891 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 1 (B.1.1.7) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2. Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021 https://doi.org/10.1016/j.cmi.2021.05.007 doi:10.1016/j.cmi.2021.05.007 33984489 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape NTD-specific nAbs showed a substantial (3-450x) decrease in neutralization potency against the recently reported highly transmissible B.1.1.7 variant of concern, whereas RBD-specific nAbs were either unaffected or showed lower decreases in potency. Graham 2021 https://doi.org/10.1016/j.immuni.2021.03.023 doi:10.1016/j.immuni.2021.03.023 33836142 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Modelling the Alpha variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 3.9x relative to wild type (5.4 vs 1.4). This is less efficient than Delta (11x vs wildtype using a P681R mutation instead). [del ~144 changed due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a co-infection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant. Liu 2021 https://doi.org/10.1101/2021.08.12.456173v3 doi:10.1101/2021.08.12.456173v3 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.7 virus has reduced neutralization activity vs wild type: 2.1x (30 sera Pfizer median 9 days post 2nd dose) and 2.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Note that Y145del was actually noted in the paper as the effect of their DNA construct, but this is equivalent at the protein level to the more commonly annotated Y144del. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Alpha (B.1.1.7) variant is 1.0x fold the wildtype in 42 COVI. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Alpha Molnupiravir (MK-4482) had ~2.75x fold drop. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 35579953 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy NVX-CoV2373 [Novavax] vaccine in phase 3 trial was 89.7% (95% CI, 80.2-94.6) effective in preventing COVID-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8-99.5) and 86.3% (71.3-93.5) against the prototype strain and B.1.1.7 variant, respectively. Heath 2021 https://doi.org/10.1101/2021.05.13.21256639 doi:10.1101/2021.05.13.21256639 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Alpha (B.1.1.7) has an IC50 fold change of 1.19x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.1.7 lineage effectiveness was observed as 29.5% (95% CI [22.9,35.5]) against infection, and 54.1% against severe/critical/fatal disease (95% CI [26.1-71.9]). Two weeks or more after 2nd dose, effectiveness climbed to 89.5% [85.9,92.3] against infection, and 100% against severe/critical/fatal disease (95% CI [81.7,100]). Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24506 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,S982A NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Lilly's LY-CoV16 showed marked reduction in neutralization of B.1.1.7. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Sera neutralized the B1.1.7 isolate with a lower potency (2-fold; 95% CL: 1.5 – 3-fold), and those with the lowest homotypic neutralizing potency had undetectable heterotypic potency (2/25). Skelly 2021 https://doi.org/10.21203/rs.3.rs-226857/v1 doi:10.21203/rs.3.rs-226857/v1 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23709,23604,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,T716I,P681H,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific replication effects In this report, by using a lower infectious dose, we demonstrate that B.1.1.7 (cultured sample Hong Kong/HKPU-00015/2021) exhibits higher infectivity and/or replication efficiency in the nasal epithelium. (Hamster model of infection) Mok 2021 https://doi.org/10.1101/2021.04.19.440414 doi:10.1101/2021.04.19.440414 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021 https://doi.org/10.48550/arXiv.2104.05560 doi:10.48550/arXiv.2104.05560 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021 https://doi.org/10.1101/2021.02.24.21251989 doi:10.1101/2021.02.24.21251989 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021 https://doi.org/10.1038/s41586-021-03426-1 doi:10.1038/s41586-021-03426-1 33723411 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. Graham 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively. Roquebert 2021 https://doi.org/10.1101/2021.03.19.21253971 doi:10.1101/2021.03.19.21253971 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. Graham 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio 341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). Frampton 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021 https://doi.org/10.1101/2021.02.24.21251989 doi:10.1101/2021.02.24.21251989 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies. Muik 2021 https://doi.org/10.1126/science.abg6105 doi:10.1126/science.abg6105 33514629 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies. Muik 2021 https://doi.org/10.1126/science.abg6105 doi:10.1126/science.abg6105 33514629 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The mortality hazard ratio associated with infection with [B.1.1.7] compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community (54906 matched pairs of participants who tested positive for SARS-CoV-2 in pillar 2 between 1 October 2020 and 29 January 2021). In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases. Challen 2021 https://doi.org/10.1136/bmj.n579 doi:10.1136/bmj.n579 33687922 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." Couzens 2021 https://doi.org/10.1101/2021.04.02.21254832 doi:10.1101/2021.04.02.21254832 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021 https://doi.org/10.1101/2021.02.24.21251989 doi:10.1101/2021.02.24.21251989 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021 https://doi.org/10.1038/s41586-021-03426-1 doi:10.1038/s41586-021-03426-1 33723411 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021 https://doi.org/10.48550/arXiv.2104.05560 doi:10.48550/arXiv.2104.05560 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021 https://doi.org/10.48550/arXiv.2104.05560 doi:10.48550/arXiv.2104.05560 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 20/29 sera after the first dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 variant of 3.2 ± 5.7. After the second dose, the GMT was markedly increased compared with the first-dose titres, with a fold change of 1.9 ± 0.9 (mean ± s.d.). Neutralization GMT of 27 subjects post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization capacity GMT of 27 subjects' sera post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021 https://doi.org/10.48550/arXiv.2104.05560 doi:10.48550/arXiv.2104.05560 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021 https://doi.org/10.1038/s41586-021-03426-1 doi:10.1038/s41586-021-03426-1 33723411 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021 https://doi.org/10.1101/2021.02.24.21251989 doi:10.1101/2021.02.24.21251989 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." Couzens 2021 https://doi.org/10.1101/2021.04.02.21254832 doi:10.1101/2021.04.02.21254832 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change. Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." Ratcliff 2021 https://doi.org/10.1101/2021.02.24.21251989 doi:10.1101/2021.02.24.21251989 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." Couzens 2021 https://doi.org/10.1101/2021.04.02.21254832 doi:10.1101/2021.04.02.21254832 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change. Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively. Roquebert 2021 https://doi.org/10.1101/2021.03.19.21253971 doi:10.1101/2021.03.19.21253971 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." Couzens 2021 https://doi.org/10.1101/2021.04.02.21254832 doi:10.1101/2021.04.02.21254832 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change. Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036). Song 2021 https://doi.org/10.1101/2021.05.04.21256655 doi:10.1101/2021.05.04.21256655 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio 341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). Frampton 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021 https://doi.org/10.1038/s41586-021-03426-1 doi:10.1038/s41586-021-03426-1 33723411 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021 https://doi.org/10.48550/arXiv.2104.05560 doi:10.48550/arXiv.2104.05560 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio 341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). Frampton 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49) Buchan 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking VSV pseudotype B.1.1.7 showed no significant difference in cell entry relative to wild type in 6 cell lines. Cell fusion proficiency was unchanged. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49) Buchan 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants. Lindstrøm 2021 https://doi.org/10.1101/2021.03.29.21254122 doi:10.1101/2021.03.29.21254122 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks. Munitz 2021 https://doi.org/10.1016/j.xcrm.2021.100264 doi:10.1016/j.xcrm.2021.100264 33899031 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Based on 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020, Rt of B.1.1.7 was 1.35x (95% CI 1.02-1.69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Graham 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks. Munitz 2021 https://doi.org/10.1016/j.xcrm.2021.100264 doi:10.1016/j.xcrm.2021.100264 33899031 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49) Buchan 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 33658326 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants. Lindstrøm 2021 https://doi.org/10.1101/2021.03.29.21254122 doi:10.1101/2021.03.29.21254122 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49) Buchan 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants. Lindstrøm 2021 https://doi.org/10.1101/2021.03.29.21254122 doi:10.1101/2021.03.29.21254122 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, but to a smaller extent than N501Y and the deletion alone. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Slight neutralization improvement on average in 16 health workers' convalescent sera. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding These key B.1.1.7 mutations as a combination neutralized slightly less well than D614G and this was noticeable in the lack of sera with high neutralizing titer for the viruses across 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,21762,21763,21764,21765,21766,21766,23399,23401,23402,23403,22915,22916,22917 H69del,H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 17.2x-fold lower (95% CI: 0.6x-0.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,21762,21763,21764,21765,21766,21766,23399,23401,23402,23403,22915,22916,22917 H69del,H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 13.0-fold lower (95% CI: 4.2x-4.6x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,22810,22811,22812,22813,22813,23009,23010,23012,23013 H69del,H69del,H69del,H69del,H69del,H69del,H69del,K417N,K417N,K417N,K417N,K417N,E484A,E484A,E484A,E484A NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Ontario, using a retrospective matched case (age, gender and onset date) study of 6,312 Omicron cases vs 8,875 Delta, the adjusted risk of hospitalization or death was 54% lower (HR=0.46, 95%CI: 0.27, 0.77) among Omicron cases, after adjusting for vaccination statis and time since 2nd shot. The ratio for >60yo was 0.55 (95%CI: 0.28-1.06), and <60yo was 0.30 (95%CI: 0.16-0.57). Ulloa 2021 https://doi.org/10.1101/2021.12.24.21268382 doi:10.1101/2021.12.24.21268382 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21761,21762,21763,21764,21765,21766,21766,23009,23010,23012,23013 H69del,H69del,H69del,H69del,H69del,H69del,H69del,E484A,E484A,E484A,E484A NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection, evidenced by a reinfection hazard ratio of 2.39 (CI95: 1.88-3.11) relative to primary infection in the initial part of South Africa's 4th covid-19 wave (November 2021). In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. [minimal variant signature for Omicron (B.1.1.529) used based on H69del PCR dropout observed in November 2021 coincident with the rise of Omicron] Pulliam 2021 https://doi.org/10.1101/2021.11.11.21266068 doi:10.1101/2021.11.11.21266068 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800 D80N NC_045512.2:g.238G>A YP_009724390.1:p.Asp80Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800 D80Y NC_045512.2:g.238G>T YP_009724390.1:p.Asp80Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This AA substitution outside the receptor binding domain in pseudotyped VSV promoted a 7.2% transduction rate in golden hamster cells, which was higher than that of human epithelial-like Huh-7 cells (6.6%). Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800,22188,22206,22597,22599,23012,23521,23522,23524,23525,23604 D80Y,I210del,D215G,R346K,R346K,E484K,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.238G>T,NC_045512.2:g.629_631del,NC_045512.2:g.644A>G,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp80Tyr,YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against A.VOI.V2 (first identified in Angola) reduced 8.0x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated that there is no free energy change (ddG) for this variant (i.e. same stability as wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 34931886 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion One individual of 30 in the study, with HLA supertype HLA*A24:02, had a linear epitope that overlaps this variant of concern. Redd 2021 https://doi.org/10.1101/2021.02.11.21251585 doi:10.1101/2021.02.11.21251585 33594378 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abolishes neutralizing activity of N-terminal-domain-directed mAb 4-19. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.351 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 71%, Day 209 54%. Detectable antibodies against B.1.351 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 79%, Day 209 58%. Detectable antibodies against B.1.351 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 63%, Day 43 100%, Day 119 71%, Day 209 79%. Decreased neutralization on some assays was seen especially in those vaccinees tested that were 71+. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 34031659 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In an Ontario long term care facility, cumulatively, weaker BNT162b2 vaccine stimulation, age/comorbidities, produced a ∼130-fold reduction in apparent neutralization titers in mean 88yo LTCH residents against Beta (B.1.351), relative to staff vaccinees against D614G wild type. 37.9% of 116 two-dose-mRNA-vaccinated residents had undetectable neutralizing antibodies to B.1.351. mRNA-1273 vaccinee sera displayed ~2 better neutralization than BNT162b2. [common defining B.1.351 mutations noted, as the manuscript does not provide details] Abe 2021 https://doi.org/10.1101/2021.08.06.21261721 doi:10.1101/2021.08.06.21261721 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, 7 of 15 neutralized this B.1.351 pseudotype that includes the L242del, and only one had titers above 100. Only one of the 15 sera achieved 80% neutralization. [compare to 5 and 1 for pseudotype without the deletion] Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 33766944 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 33766944 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~10-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~3 fold without the deletion] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were significant, but ~500x weaker than in previously infected patients after first dose. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 33766944 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v3 reduced 8.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Beta (B.1.351) variant is 0.4x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A two-dose regimen of (AstraZeneca) ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, vaccine efficacy against severe Covid-19 is undetermined. Madhi 2021 https://doi.org/10.1101/2021.02.10.21251247 doi:10.1101/2021.02.10.21251247 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 33972942 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 33972942 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination. Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Unlike wild type or B.1.1.7, B.1.351 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. PG: The virus used in these expriments has a non-typical deletion+sub in the 242 region. Montagutelli 2021 https://doi.org/10.1101/2021.03.18.436013 doi:10.1101/2021.03.18.436013 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Beta (B.1.351) has an IC50 fold change of 0.13x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Beta (B.1.351) has an IC50 fold change of 0.15x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001). Zhou 2021 http://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 33730597 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001). Zhou 2021 http://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 33730597 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~6x cleavage of S2 relative to WA1 (D614G) wildtype by Beta variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but A701V is downstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Beta Molnupiravir (MK-4482) had ~1.75x fold drop. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 35579953 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.351 v1 virus has reduced neutralization activity vs wild type: 34.5x (30 sera Pfizer median 9 days post 2nd dose) and 27.7x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Beta (B.1.351) has an IC50 fold change of 0.13x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001). Zhou 2021 http://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 33730597 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination. Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Compared to Alpha (B.1.1.7) variant, odds of progressing to severe disease were 1.24-fold (95% CI: 1.11-1.39) higher for Beta. Odds of progressing to critical disease were 1.49-fold (95% CI: 1.13-1.97) higher. Odds of COVID-19 death were 1.57-fold (95% CI: 1.03-2.43) higher. Abu-Raddad 2021 https://doi.org/10.1101/2021.08.02.21261465 doi:10.1101/2021.08.02.21261465 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 34 convalescent cases 4–9 weeks following infection in June 2020, before the emergence of B.1.1.7, neutralization titers against B.1.351 were, on average, 13.3-fold reduced compared with an early Victoria sample (p < 0.0001). Significantly, 18 of 34 samples failed to reach 50% neutralization at a plasma dilution of 1:20, with a number showing a near total reduction of neutralization activity. In 13 convalescent cases 4–9 weeks following infection with B.1.1.7, neutralization titers against B.1.351 were, on average, 3.1-fold reduced compared with an early Victoria sample (p < 0.0001). Zhou 2021 https://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 33730597 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Testing against B.1.351 the 20 most effective mAbs (19 anti-RBD, 1 anti-NTD) from a screen of 377 against wild type, 4 of 20 antibodies had >10-fold fall in neutralization titers, with most of these showing a complete knockout of activity. This is in line with the key roles of K417, E484, and N501, in particular E484, in antibody recognition of the ACE2 interaction surface of the RBD. Regeneron mAb cocktail: The neutralization of REGN10987 was unaffected by B.1.351, while REGN10933 was severely impaired (773-fold). AstraZeneca mAb cocktail: Neutralization by the AZ pair of antibodies was little affected on B.1.351 compared with Victoria. Zhou 2021 https://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 33730597 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.351 defining mutations: Significant shift to infection in those without pre-existing conditions (79.6% vs 89% for non-VOC cases). Significant increase in hospitalization rate (19.3% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.3% vs 0.6% for non-VOC cases). PG: seems to be different notations around the LAL deletion, using the minimal shared definition to catch as many as possible. Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 33890566 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The B.1.351 variant constellation causes an ∼20-fold increase in affinity for ACE2 compared with Wuhan RBD, which may influence transmissibility. Zhou 2021 https://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 33730597 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccine plasma neutralization of B.1.351-spike virus was nominally robust but lower (~3x) than other variants of concern. Liu 2021 https://doi.org/10.1056/NEJMc2102017 doi:10.1056/NEJMc2102017 33684280 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) humoral response durability In a prospective study of 107 hospitalized patients, decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7 and P.1 variants for at least 6 months (last of two samples taken) in patients previously hospitalized for COVID-19. A weaker protection was however observed for the B.1.351 variant. Betton 2020 https://doi.org/10.1093/cid/ciab308 doi:10.1093/cid/ciab308 33851216 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Beta (B.1.351) has an IC50 fold change of 0.88x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using B.1.351 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 33766944 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~3-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~10 fold with L242del] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were signficiant, but >100x weaker than in previously infected patients after first dose. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 33766944 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, one third (5/15) of sera neutralized this B.1.351 pseudotype and only three had ID50 titers above 100. Only two of the 15 sera achieved 80% neutralization. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 33766944 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission. Yinda 2021 https://doi.org/10.1101/2021.05.05.442780 doi:10.1101/2021.05.05.442780 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence Inoculation with the B.1.351 isolate resulted in lower clinical scores in 6 rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. Our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity. Munster 2021 https://doi.org/10.1101/2021.05.07.443115 doi:10.1101/2021.05.07.443115 34382034 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 4 health care workers in the 20's and 30's with no underlying conditions and seropositivity or confirmed 2020 SARS-CoV-2 infections were confirmed to have B.1.351 infection during a Februrary 2021 hospital outbreak in Luxembourg. Symptoms were mostly mild on first infection, and milder on second infection. Staub 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.18.2100423 doi:10.2807/1560-7917.ES.2021.26.18.2100423 33960291 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission. Yinda 2021 https://doi.org/10.1101/2021.05.05.442780 doi:10.1101/2021.05.05.442780 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351. 2021 https://www.fda.gov/media/146217/download False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer Solfrosi 2021 https://doi.org/10.1084/jem.20202756 doi:10.1084/jem.20202756 33909009 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.351 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the B.1.351 variants used, using the most popular as a stad in] McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In a Syrian hamster model, B.1.351 variant virus had >4x reduction in YRNT90 (measure of neutralization) using wild type convalescent sera. PG: Note that exact sequence for B.1.351 used was not disclosed. Cochin 2021 https://doi.org/10.1101/2021.04.19.440435 doi:10.1101/2021.04.19.440435 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy During an outbreak of SARS-CoV-2 501Y.V2 in a nursing home, all non-vaccinated residents (5/5) versus half of those fully vaccinated 2-5 weeks prior with BNT162b2 (13/26) were infected. Two of 13 vaccinated versus 4 of 5 non-vaccinated residents presented severe disease. BNT162b2 did not prevent the outbreak, but reduced transmission and disease severity. Among the 13 fully vaccinated residents who were infected, 2 (15.4%) presented with an asymptomatic disease, 9 (69.2%) developed mild to moderate symptoms, and 2 (15.4%) progressed to severe disease with fatal evolution secondary to acute respiratory distress syndrome (ARDS). There was no relationship between anti-S antibody levels at diagnosis and disease severity. Overall, the proportion of residents with severe disease in the non-vaccinated group (4/5) was higher than that in the vaccinated group (2/13). Only 1 vaccinated staff, but 10 unvaccinated were infected in the outbreak (no severe disease). Bailly 2021 https://doi.org/10.1093/cid/ciab446 doi:10.1093/cid/ciab446 33993228 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer Solfrosi 2021 https://doi.org/10.1084/jem.20202756 doi:10.1084/jem.20202756 33909009 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.351 v3 virus has reduced neutralization activity vs wild type: 42.4x (30 sera Pfizer median 9 days post 2nd dose) and 19.2x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351. 2021 https://www.fda.gov/media/146217/download False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 33822491 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351. 2021 https://www.fda.gov/media/146217/download False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 33851181 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.351 in 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.351 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0020 for moderate resistance. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.351 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. B.1.1.351 variant constellation ablates Class 3 N-terminal domain targeting antibodies COV2-2489 and COV2-2676 (the only two tested). Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H] Supasa 2021 https://doi.org/10.1016/j.cell.2021.02.033 doi:10.1016/j.cell.2021.02.033 33743891 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccine elicited antibodies neutralized virus with the B.1.351 spike protein had an average 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness VSV pseudotype B.1.351 entry mediated by the S proteins of the B.1.351 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.351 lineage effectiveness was observed as 16.9% (95% CI [10.4,23.0]) against infection, and 0% against severe/critical/fatal disease (95% CI [0-19.0]). Two weeks or more after 2nd dose, effectiveness climbed to 75.0% [70.5,78.9] against infection, and 100% against severe/critical/fatal disease (95% CI [73.7,100]). Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 33948601 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.351 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding VSV pseudotype B.1.351 showed 7.86-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections). Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking VSV pseudotype B.1.351 showed slight decrease in cell entry relative to wild type in 263T-ACE2 (kidney) cell line, and slight increase in Calu-3 (lung). Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abrogates Bamlanivimab, Etesevimab, or their combined use neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Approximately 6-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 33794143 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In one of eight cell lines tested (293T lung cells), a modest increase in cell entry was observed. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H] Supasa 2021 https://doi.org/10.1016/j.cell.2021.02.033 doi:10.1016/j.cell.2021.02.033 33743891 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846 T95I NC_045512.2:g.284C>T YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 65yo female with no severe Covid-19 risk factors tested positive 36 days after second dose of BNT162b2 (Pfizer) vaccine. Presented with fatigue, sinus congestion, and a headache developed; her symptoms plateaued and began to resolve six days later. [Mising genome coverage in regions of Spike covering clinically relevant mutations K417T, L452R, E484K, A701V, D796H, N501Y] Hacisuleyman 2021 https://doi.org/10.1056/NEJMoa2105000 doi:10.1056/NEJMoa2105000 33882219 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22317,22319,22320,23399,23401,23402,23403 T95I,D253G,D253G,D253G,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio B.1.526 (Iota) substantially increased IFR in older adults: by 46% (95% CI: 7.4 – 84%) among 45-64 year-olds, 82% (95% CI: 20 – 140%) among 65-74 year-olds, and 62% (95% CI: 45 – 80%) among 75+ during Nov 2020 – Apr 2021, compared to baseline IFR estimated for preexisting variants. [minimum clade defining mutations listed] Yang 2021 https://doi.org/10.1101/2021.08.04.21261596 doi:10.1101/2021.08.04.21261596 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against B.1.621. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera from vaccinees [ChAdOx1 and BNT162b2 primarily used in UK] shows decreased ability to neutralize B.1.621 compared to first wave virus and Alpha, with a magnitude of change similar to Beta. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 69 test-positive were Mu. Two dose vaccine efficacy against Mu was 90.4% (73.9-96.5%), one dose VE was 45.8% (0.0-88.9%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Sera from individuals who have been infected with Delta does not have strong neutralising activity against B.1.621 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 33826815 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 12.4x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. [This is a greater reduction than Beta @ 8.2x] Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Using live B.1.621 virus and a cytopathic effect-based assay, sera from 37 Pfizer/BioNTech BNT162b2 vaccinees collected 10-20 days post-booster showed significantly lower (95) but still ""robust"" neutralization than against ancestral B.1 virus (107)." Messali 2021 https://doi.org/10.1002/jmv.27247 doi:10.1002/jmv.27247 34329486 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 7.6x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. [This is a greater reduction than Beta @ 6.3x] Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403 T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 4.4-fold lower (95% CI: 4.3x-4.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403 T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 1.5x-fold lower (95% CI: 0.05x-0.07x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,23012,23271,23399,23401,23402,23403,23604,23948 T95I,E484K,A570D,D614G,D614G,D614G,D614G,P681H,D796H NC_045512.2:g.284C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2386G>C YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp796His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 51yo female with no severe COVID-19 risk factors tested positive 19 days after second dose of mRNA-1273 (Moderna) vaccine. Presented with sore throat, congestion, and headache developed; the next day she lost her sense of smell. Symptoms resolved over a one week period. Serum obtained 4 days after symptom onset was tested for neutralization against wild-type virus, the E484K mutant, and the B.1.526 variant. It was equally effective against each. These data suggest that the antibody response recognized these variants but was nonetheless insufficient to prevent a breakthrough infection. The virus detected matched neither B.1.1.7 nor B.1.526 VOC strains in wide circulation in New York at the time of infection, though shared some mutations. Hacisuleyman 2021 https://doi.org/10.1056/NEJMoa2105000 doi:10.1056/NEJMoa2105000 33882219 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,23399,23401,23402,23403 T95I,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21855 S98F NC_045512.2:g.293C>T YP_009724390.1:p.Ser98Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly enhanced the transduction rate in raccoon dog (Nyctereutes procyonoides) kidney (62.4%) and Rickett’s big-footed bat (Myotis pilosus) kidney (45.0%) cell cultures compared to epithelial-like human Huh-7 cells (38.9%). Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21929 A123S NC_045512.2:g.367G>T YP_009724390.1:p.Ala123Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected in passage with mAb COV2-2489 during alanine mutagenesis antibody mapping experiment. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 33501445 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21969 C136Y NC_045512.2:g.407G>A YP_009724390.1:p.Cys136Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massively decreases N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21969 C136Y NC_045512.2:g.407G>A YP_009724390.1:p.Cys136Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected twice in passage with mAb COV2-2489. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 33501445 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. [PG: This mutation is adjacent to a well known deletion, which may confound the significance of this variant] Lucaci 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events These variants dominate in mink infections in North America, sometime supplemented with F486L. The Y453F variant found in other jurisdictions in mink infections is notably absent in North America. 2021 https://doi.org/10.1101/2021.03.18.21253734v3 doi:10.1101/2021.03.18.21253734v3 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Relative to B.1, Kappa (B.1.617.1) shows 5.71x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Average 2x neutralization efficiency decrease against sera from 26 Phase II trial Covaxin (BBV152) vaccine recipents. Very similar to B.1.1.7 (~2x) in the same study, and the neutralization from 17 sera of natural infections across B1 lineages. Yadav 2021 https://doi.org/10.1101/2021.04.23.441101 doi:10.1101/2021.04.23.441101 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.1) showed a 1.12x increase in binding (KD) relative to D614G, but described as ""not significant"". [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cluster of B.1.617[.1] infections related to travel from India to USA, one patient with mild symptoms had received their second dose of Pfizer vaccine more than two weeks before the infection [i.e. vaccine breakthrough]. Verghese 2021 https://doi.org/10.1128/JCM.00741-21 doi:10.1128/JCM.00741-21 33952596 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.617.1) showed a 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.617.1) showed a 1.79x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~3.5x cleavage of S2 relative to WA1 (D614G) wildtype by Kappa (B.1.617.1) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~4.5x for closely related Delta B.1.617.2 also with P681R at the cleavage site). Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1, Kappa (B.1.617.1) shows mean 1.97x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Kappa (B.1.617.1) has an IC50 fold change of 2.3x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Kappa (B.1.617.1) has an IC50 fold change of 0.13x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Kappa (B.1.617.1) has an IC50 fold change of 80.2x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Kappa (B.1.617.1) has an IC50 fold change of 0.68x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.2 has an IC50 fold change of 0.04x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Omicron BA.2 has an IC50 fold change of 0.09x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.2 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Omicron BA.2 has an IC50 fold change of 0.08x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.2 has an IC50 fold change of 0.07x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Omicron BA.2 variant is 0.8x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.2 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21974 D138Y NC_045512.2:g.412G>T YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.43 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21977 P139S NC_045512.2:g.415C>T YP_009724390.1:p.Pro139Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2:g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2:g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected once in passage with mAb COV2-2676. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 33501445 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2:g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2:g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990 Y145del,Y145del NC_045512.2:g.432_434del,NC_045512.2:g.432_434del YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990 Y145del,Y145del NC_045512.2:g.432_434del,NC_045512.2:g.432_434del YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient. McCarthy 2021 https://doi.org/10.1126/science.abf6950 doi:10.1126/science.abf6950 33536258 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990,21993,21995,23012,23399,23401,23402,23403 Y145del,Y145del,H146del,H146del,E484K,D614G,D614G,D614G,D614G NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.436_438del,NC_045512.2:g.436_438del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.His146del,YP_009724390.1:p.His146del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Normalized for particle number, on ACE2.293T cells showed that the B.1.618 spike protein was about as infective as D614G wild type. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21993,21995 H146del,H146del NC_045512.2:g.436_438del,NC_045512.2:g.436_438del YP_009724390.1:p.His146del,YP_009724390.1:p.His146del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient. McCarthy 2021 https://doi.org/10.1126/science.abf6950 doi:10.1126/science.abf6950 33536258 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21997,21998,21999,22000,22001 K147E,K147E,K147E,K147E,K147E NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21997,21998,21999,22000,22001 K147E,K147E,K147E,K147E,K147E NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2X28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21998 H146Y NC_045512.2:g.436C>T YP_009724390.1:p.His146Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Massive reduction in 4A8 monoclonal antibody EC50 (i.e. ablated recognition), but much milder effect on mAbs within antigenic supersite ""i""" McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22001 K147Q NC_045512.2:g.439A>C YP_009724390.1:p.Lys147Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22002 K147T NC_045512.2:g.440A>C YP_009724390.1:p.Lys147Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22002 K147T NC_045512.2:g.440A>C YP_009724390.1:p.Lys147Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massively decreases N terminal domain antigen recognition by supersite i mAbs S2M28, S2X28, S2X333, 4A8 (but not S2L28). McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22003 K147N NC_045512.2:g.441A>T YP_009724390.1:p.Lys147Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22005 N148S NC_045512.2:g.443A>G YP_009724390.1:p.Asn148Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong positive selection (up to 72% of supernatant sequences) under six rounds of COV47 convalescent plasma passage Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22010 K150E NC_045512.2:g.448A>G YP_009724390.1:p.Lys150Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong positive selection (up to 40% of supernatant sequences) under three rounds of COV47 convalescent plasma passage Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22010 K150E NC_045512.2:g.448A>G YP_009724390.1:p.Lys150Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22011 K150T NC_045512.2:g.449A>C YP_009724390.1:p.Lys150Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 22% of supernatant sequences) after COV47 convalescent plasma assay Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22011 K150R NC_045512.2:g.449A>G YP_009724390.1:p.Lys150Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 18% of supernatant sequences) under two rounds of COV47 convalescent plasma passage Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22016,22016 W152R,W152R NC_045512.2:g.454T>A,NC_045512.2:g.454T>C YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For NTD-binding neutralizing antibody ADI-56479 this mutation causes a 1000x drop in neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22016,22016 W152R,W152R NC_045512.2:g.454T>A,NC_045512.2:g.454T>C YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22018 W152C NC_045512.2:g.456G>T YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Pseudoviruses carrying the W152C mutation demonstrated small increases in cell entry compared to D614G alone in 293T cells and human airway organoids. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22018 W152C NC_045512.2:g.456G>T YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The W152C mutation reduced recognition of six NTD neutralizing mAbs, including a complete loss of binding for two of them, with a complementary pattern to that observed for S13I (also found in lineage B.1.427/B.1.429) out of 11 neutralizing mAbs evaluated. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022 E154K NC_045512.2:g.460G>A YP_009724390.1:p.Glu154Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022,22915,22916,22917,23012,23399,23401,23402,23403,23604 E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Approximately 2-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022,22915,22916,22917,23012,23399,23401,23402,23403,23604 E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abrogates Bamlanivimab neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Significant decrease in combined Etesevimab+Bamlanivimab neutralization except at the highest concentration measured. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022,22915,22916,22917,23012,23399,23401,23402,23403,23604 E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In two of eight cell lines tested (Caco-2 intenstinal and Calu-3 lung), a modest increase in cell entry was observed. This increase was not observed in a Calu-3 cell line with overexpressed ACE2. [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022,22915,22916,22917,23012,23399,23401,23402,23403,23604 E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 15 Pfizer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~3x (compared to ~11x for B.1.351). [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034 R158G,R158G NC_045512.2:g.467_472del,NC_045512.2:g.472A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22033,23012,23604 F157L,E484K,P681R NC_045512.2:g.471C>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against A.23.1-v2 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22033,23604 F157L,P681R NC_045512.2:g.471C>A,NC_045512.2:g.2042C>G YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against A.23.1-v1 reduced 1.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22036 R158S NC_045512.2:g.474A>T YP_009724390.1:p.Arg158Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected three times in passage with mAb COV2-2489. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 33501445 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:03. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type C*07:02. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DPB1*04:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:02. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:02. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*16:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*07:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22107,22111 Q183H,Q183H NC_045512.2:g.549G>T,NC_045512.2:g.549G>T YP_009724390.1:p.Gln183His,YP_009724390.1:p.Gln183His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 33176080 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22132 R190S NC_045512.2:g.570G>T YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.69 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604 R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in B.1.640.2 variant was ~1000x folds more significant in 8 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 35581351 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604 R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1.640.2 variant was ~5.6x folds more significant in 9 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 35581351 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22188,23399,23401,23402,23403 I210del,D614G,D614G,D614G,D614G NC_045512.2:g.629_631del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection A 42yo Iranian male was reinfected with B.1.36 lineage virus 128 days after infection with genetically distinct B.1.36 virus, with negative PCR tests in between. In the first instance patient presented with cough, headache, severe diarrhea. In the second instance symptoms were more severe: body pain, shortness of breath, headache and anosmia. Anti-SARS-CoV-2 IgG and IgM tests were negative after both episodes. [Non-seroconversion may be associated with elevated risk of re-infection] [I210del is a homoplasy that has appeared in several disparate parts of the global phylogenetic tree, including A and B lineages, primarily in LMICs] Salehi-Vaziri 2021 https://doi.org/10.1016/j.virusres.2021.198421 doi:10.1016/j.virusres.2021.198421 33836204 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:01. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 34931886 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*13:02. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 34931886 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:02. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 34931886 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.98 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22224,22227 A222V,A222V NC_045512.2:g.665C>T,NC_045512.2:g.665C>T YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22224,22227,23399,23401,23402,23403 A222V,A222V,D614G,D614G,D614G,D614G NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) humoral response durability 27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3), i.e. with a 9 month interval. Both cases were mild. No significant differences in the neutralizing capacity of the two lineages were observed in 4 sera taken (1 pre-reinfection, three post-reinfection). Neutralizing antibody titres (IC50) before and immediately after re-infection were <300 against both strains, and jumped >7x upon re-infection. Viral titres were also higher in the second case. Second case also includes N:p.A220V Brehm 2021 https://doi.org/10.3390/v13040661 doi:10.3390/v13040661 33921216 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22224,22227,23399,23401,23402,23403 A222V,A222V,D614G,D614G,D614G,D614G NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3). Both cases were mild. Second case also includes N:p.A220V Brehm 2021 https://doi.org/10.3390/v13040661 doi:10.3390/v13040661 33921216 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22293 L244S NC_045512.2:g.731T>C YP_009724390.1:p.Leu244Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22301 S247R NC_045512.2:g.739A>C YP_009724390.1:p.Ser247Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22304 Y248H NC_045512.2:g.742T>C YP_009724390.1:p.Tyr248His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22314 P251L NC_045512.2:g.752C>T YP_009724390.1:p.Pro251Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317 G252D NC_045512.2:g.755G>A YP_009724390.1:p.Gly252Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317,22319,22320 D253G,D253G,D253G NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317,22319,22320 D253G,D253G,D253G NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22319 D253Y NC_045512.2:g.757G>T YP_009724390.1:p.Asp253Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22323 S254Y NC_045512.2:g.761C>A YP_009724390.1:p.Ser254Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22323 S254F NC_045512.2:g.761C>T YP_009724390.1:p.Ser254Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22326 S255F NC_045512.2:g.764C>T YP_009724390.1:p.Ser255Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22328,22329,22331 G257S,G257S,G257S NC_045512.2:g.769G>A,NC_045512.2:g.769G>A,NC_045512.2:g.769G>A YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334 W258R NC_045512.2:g.772T>C YP_009724390.1:p.Trp258Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334 W258R NC_045512.2:g.772T>C YP_009724390.1:p.Trp258Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 33469588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334,22879,22881,22882,22882,22904,22910,23012 W258R,N440K,N440K,N440K,N440K,N450D,N450D,E484K NC_045512.2:g.772T>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22340 A260T NC_045512.2:g.778G>A YP_009724390.1:p.Ala260Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22344 G261D NC_045512.2:g.782G>A YP_009724390.1:p.Gly261Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Multiple mink but no humans on one farm in Denmark, potential adaptation. Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 33172935 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22377 P272L NC_045512.2:g.815C>T YP_009724390.1:p.Pro272Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*02:01. Dolton 2021 https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf doi:10.1101/2021.06.21.21259010v2.full.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22377 P272L NC_045512.2:g.815C>T YP_009724390.1:p.Pro272Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*08:01. Dolton 2021 https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf doi:10.1101/2021.06.21.21259010v2.full.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 1.2x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.3 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22583 V341I NC_045512.2:g.1021G>A YP_009724390.1:p.Val341Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22595,22596,22597,22599 R346T,R346T,R346T,R346T NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22595,22596,22597,22599 R346T,R346T,R346T,R346T NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.15 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22595,22596,22597,22599,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22939,22942,22942,22992,23009,23010,23012,23013,23027,23029,23030,23031,23053,23054,23055,22992,22995,23060,23061,23062,23063,23071,23074,23075 R346T,R346T,R346T,R346T,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N460K,N460K,N460K,S477N,E484A,E484A,E484A,E484A,F490S,F490S,F490S,F490S,Q498R,Q498R,Q498R,T478K,T478K,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The hACE2-binding affinity of XBB.1.5 RBD has a dissociation constant KD of 3.4 nM, where S486P is the distinguishing Spike mutation vs parent XBB.1 RBD with a much weaker KD (19 nM), as measured by surface plasmon resonance (SPR) assays. Yue 2023 https://doi.org/10.1101/2023.01.03.522427 doi:10.1101/2023.01.03.522427 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346K,R346K NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346I,R346I NC_045512.2:g.1037G>T,NC_045512.2:g.1037G>T YP_009724390.1:p.Arg346Ile,YP_009724390.1:p.Arg346Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Provides ~80% escape from mAb COV2-2130, even though its appearance in culture is formed without selective mAb pressure. Dong 2021 https://doi.org/10.1101/2021.01.27.428529 doi:10.1101/2021.01.27.428529 33532768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346K,R346K NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation, which has emerged in some Omicron sequences, has a 0.7x reduction in neutralization activity with Sotrovimab in a VSV model on Vero E6 cells. [Omicron sequences with R346K may very well have a non-additive neutralization rather than 2.7x+0.7x = 3.4x] Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346K,R346K NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 53% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 2/3 antibody C603. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 2/3 antibody C603. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Positive selection (up to 30% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22622 N354D NC_045512.2:g.1060A>G YP_009724390.1:p.Asn354Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.13 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22624 N354K NC_045512.2:g.1062C>A YP_009724390.1:p.Asn354Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22627,22629 K356T,K356T NC_045512.2:g.1067A>C,NC_045512.2:g.1067A>C YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.14 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22629 K356R NC_045512.2:g.1067A>G YP_009724390.1:p.Lys356Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22632 R357K NC_045512.2:g.1070G>A YP_009724390.1:p.Arg357Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.18 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2:g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as ""stabilizing"" since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2:g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.72 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2:g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as ""stabilizing"" since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2:g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22661 V367I NC_045512.2:g.1099G>A YP_009724390.1:p.Val367Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22679 S373P NC_045512.2:g.1117T>C YP_009724390.1:p.Ser373Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Reduce affinity for mildly cross-reactive CR3022 (2003 pandemic SARS monoclonal antibody cross-reactive to SARS-CoV-2) Long 2020 https://doi.org/10.1128/mBio.02707-20 doi:10.1128/mBio.02707-20 33127862 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22679,23009,23010,23012,23013 S373P,E484A,E484A,E484A,E484A NC_045512.2:g.1117T>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility On December 7, 2021 the estimate of Omicron effective reproduction rate (Rt) is 3.12 [presumably R0 is higher], compared to 1.12 for the dominant Delta VOC at that time. [shorthand of variant list shraed by all contemporary BA lineage used here] 2021 https://doi.org/10.47326/ocsat.dashboard.2021.1.0 doi:10.47326/ocsat.dashboard.2021.1.0 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22686 S375F NC_045512.2:g.1124C>T YP_009724390.1:p.Ser375Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. Lucaci 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22696 K378N NC_045512.2:g.1134G>T YP_009724390.1:p.Lys378Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for mildly neutralizing COV2-2677 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23402,23403 P384L,D614G,D614G,D614G,D614G NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23402,23403 P384L,D614G,D614G,D614G,D614G NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23402,23403 P384L,D614G,D614G,D614G,D614G NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22745 V395I NC_045512.2:g.1183G>A YP_009724390.1:p.Val395Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22766 I402V NC_045512.2:g.1204A>G YP_009724390.1:p.Ile402Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22783,22784,22785,22786,22786 R408S,R408S,R408S,R408S,R408S NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22783,22784,22785,22786,22786,23009,23010,23012,23013,23060,23061,23062,23063 R408S,R408S,R408S,R408S,R408S,E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a study of 481 vaccinees going from lowest to highest infection rate, 2 doses of CoronaVac and 1 dose of BNT162b2 had the lowest infection rate at 6.3%, then it was 3 doses of BNT162b2 having a infection rate of 16.6%. 2 and 3 doses of CoronaVac had 48.6% and 20.6% infection rate respectively. 2 doses of BNT162b2 has the highest infection rate at 49.2%. Zhou 2022 https://doi.org/10.1101/2022.05.09.491254 doi:10.1101/2022.05.09.491254 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotyped virus model ablates binding by RBD-directed mAbs CB6 and 910-30 (targeting the inner side of the RBD). Pseudotyped virus model impairs binding by RBD-directed mAbs 4-20 and REGN10933. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 1.1 fold drop in IC50 of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The K417N mutation decreased the affinity ~4 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs) Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs) Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C682, and to a lesser extent C614 and C660 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects >20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against IgG1 monoclonal antibody ab1. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.86 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~6x binding against this isolated mutation. Estesevimab lost ~100x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 7.5 fold decrease in KD value for antibody binding of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 1.5 fold decrease in KD value of antibody binding of ACE2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 3-fold decrease in affinity compared to wild-type RBD on the cell surface (Kd = 145.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 19 convalescent human sera ~1mo post infection, Two-tailed Wilcoxon matched-pairs signed-rank test shows mild resistance P=0.0361. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 36.9 fold decrease in KD value for antibody binding of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape "27% of 44 early pandemic exposure convalescent plasma/sera lose all activity against a RBD triple mutant pseudovirus (RBD mutatants of the 501Y.V2 ""South African"" lineage), while only 23% retained high titres" Wibmer 2021 https://doi.org/10.1101/2021.01.18.427166 doi:10.1101/2021.01.18.427166 33501446 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" Wibmer 2021 https://doi.org/10.1101/2021.01.18.427166 doi:10.1101/2021.01.18.427166 33501446 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" Wibmer 2021 https://doi.org/10.1101/2021.01.18.427166 doi:10.1101/2021.01.18.427166 33501446 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of the B.1.351 RBD variants for ACE2 increased by 3.7 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 1.4-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.351 key variants lentivirus. Compare to 8.8-fold reduction against cultured B.1.351 virus. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 33851185 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM). Ramanathan 2021 https://doi.org/10.1101/2021.02.22.432359 doi:10.1101/2021.02.22.432359 33655251 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y. Laffeber 2021 https://doi.org/10.1101/2021.02.22.432357 doi:10.1101/2021.02.22.432357 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021 https://doi.org/10.1101/2021.03.04.433887 doi:10.1101/2021.03.04.433887 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y. Laffeber 2021 https://doi.org/10.1101/2021.02.22.432357 doi:10.1101/2021.02.22.432357 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021 https://doi.org/10.1101/2021.03.04.433887 doi:10.1101/2021.03.04.433887 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021 https://doi.org/10.1101/2021.03.04.433887 doi:10.1101/2021.03.04.433887 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021 https://doi.org/10.1101/2021.03.04.433887 doi:10.1101/2021.03.04.433887 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM). Ramanathan 2021 https://doi.org/10.1101/2021.02.22.432359 doi:10.1101/2021.02.22.432359 33655251 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from B.1.351. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y. Laffeber 2021 https://doi.org/10.1101/2021.02.22.432357 doi:10.1101/2021.02.22.432357 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 33619479 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load B.1.351 and P.1 samples showed average Ct cycle threshold of 22.2 vs 23 for wildtype (i.e. ~60% higher viral load) comparing 3360 and 22535 samples respectively. Roquebert 2021 https://doi.org/10.1101/2021.03.19.21253971 doi:10.1101/2021.03.19.21253971 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibodies ab8 and IgG1 ab1. Complete loss for the same antibodies was also observed against S1 pseudotyped and full Spike protein trimers with both B.1.351 and P.1 lineage variants, with slight binding signal for P.1 against IgG1 at the highest concentration tested (1uM). Complete loss of neutralization by these two antibodies was also observed. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This combination showed ~3x increase binding to ACE2 vs wild type, about half that of the B.1.1.7 lineage, suggesting that the K417N mutation is slightly detrimental to ACE2 binding, probably as a result of disrupting the salt bridge formed with ACE2 residue D30 Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In Moderna vaccinee sera, 2.7x reduction in neutralization, and 6.4 for the full B.1.351 Spike mutation complement, but despite the observed decreases, titers in human vaccinee sera against the B.1.351 variant remained at clinically significant level of ~1/300. Wu 2021 https://doi.org/10.1101/2021.01.25.427948 doi:10.1101/2021.01.25.427948 33501442 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China). Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility 36,590 variant-specific RT-PCR tests were performed on samples collected between April 12 and May 7, 2021 in France to compare variant spread. Compared to January to March 2021, B.1.351 variant had a significant transmission advantage over B.1.1.7 in some regions (15.1 to 16.1% in Île-de-France and 16.1 to 18.8% in Hauts-de-France). This shift in transmission advantage is consistent with the immune evasion abilities of B.1.351 and the high levels of immunization in these regions. Roquebert 2021 https://doi.org/10.1101/2021.05.12.21257130 doi:10.1101/2021.05.12.21257130 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure. Pearson 2021 https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant of key B.1.351 lineage mutations showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China). Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure. Pearson 2021 https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Average ~10-fold reduction in neutralization efficacy in convalescent sera of 16 health workers infected in Spring 2020. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) with enrollment June 24 and November 9, 2020 from ~2000 HIV-negative 18-64 year olds (1:1 placebo to treatment), incidence of serious adverse events 14 or more days post- 2nd dose was balanced between the vaccine and placebo groups. A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed 3.5x reduction in neutralization (ID50) for B.1.351 RBD pseudotype HIB-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a similar 3.2x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera). Madhi 2021 https://doi.org/10.1056/NEJMoa2102214 doi:10.1056/NEJMoa2102214 33725432 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 2 (B.1.351) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2. Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abolished neutralization by mAbs CQ026 and CQ038, greatly diminished neutralization by CQ012 and CQ046. Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23041,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trachea viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~750x fold drop in the R3P1-E4 antibody in comparison to the IgG control. Li 2022 https://doi.org/10.1186/s13578-022-00794-7 doi:10.1186/s13578-022-00794-7 35581593 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23041,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Lung viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~2266x fold drop in the R3P1-E4 antibody in comparison to the IgG control. Li 2022 https://doi.org/10.1186/s13578-022-00794-7 doi:10.1186/s13578-022-00794-7 35581593 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23041,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness 100% of the 5 8‑month‑old male R3P1-E4 antibody treated mice suvived 14 days after infection while only 60% the control group mice survived 5 days post infection. Li 2022 https://doi.org/10.1186/s13578-022-00794-7 doi:10.1186/s13578-022-00794-7 35581593 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~5x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied] Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (no synergy as level approx. that of N501Y alone). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 57.1 fold decrease in KD value for antibody binding of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.64 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 1.1 fold decrease in KD value of antibody binding of ACE2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.25 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In vitro selection against class 1 antibody C682 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The K417T mutation decreased the affinity ~2 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~16x binding against this isolated mutation. Estesevimab lost ~16x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 2.9 fold decrease in KD value for antibody binding of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 2.6 fold increase in IC50 of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w 34244522 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,23012,23060,23061,23062,23063 K417T,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from P.1. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,23012,23060,23061,23062,23063 K417T,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of the P.1 RBD variants for ACE2 increased by 5.3 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The KD for the pseudotyped P.1-ACE2 interaction is 4.8 nM, showing that binding to P.1 is essentially indistinguishable from B.1.351 (4.0 nM), which binds with ~19x greater affinity that wild type. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 33852911 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22851 T430I NC_045512.2:g.1289C>T YP_009724390.1:p.Thr430Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22865 A435S NC_045512.2:g.1303G>T YP_009724390.1:p.Ala435Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to neutralizing mAb H014 (on D614G background) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The N440K variant produced ten times higher infectious viral titers than a prevalent A2a strain, and over 1000 folds higher titers than a much less prevalent A3i strain prototype in Caco2 cells. Interestingly, A3i strain showed the highest viral RNA levels, but the lowest infectious titers in the culture supernatants, indicating the absence of correlation between the RNA content and the infectivity of the sample. Tandel 2021 https://doi.org/10.1101/2021.04.30.441434 doi:10.1101/2021.04.30.441434 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 0.7x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects N501Y substitution decreased the neutralizing and binding activities of CB6 and increased that of BD-23 Cheng 2021 https://doi.org/10.1186/s12985-021-01554-8 doi:10.1186/s12985-021-01554-8 33910569 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Positive selection (up to 45% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, eliminated in subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 3 antibody C669 mildly selected for the emergence of the N440K mutation in vitro (in contrast to N440H which caused mild escape in Class 1/2 mAb C653). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882,23399,23401,23402,23403 N440K,N440K,N440K,N440K,D614G,D614G,D614G,D614G NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection A 47yo Indian male was reinfected with B.1.36 lineage virus in September 2020 after infection with genetically distinct B.1.36 virus in July, with negative PCR tests in between. While the forst episode was asymptomatic, the second included fever, cough, and malaise. The second case additionally contained stopgain ORF3a:E261* Rani 2021 https://doi.org/10.1002/jmv.26997 doi:10.1002/jmv.26997 33818797 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444T NC_045512.2:g.1331A>C YP_009724390.1:p.Lys444Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444R NC_045512.2:g.1331A>G YP_009724390.1:p.Lys444Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Identified in 6/20 replicates of recombinant VSV growth in the presence of mAb COV2-2130. Dong 2021 https://doi.org/10.1101/2021.01.27.428529 doi:10.1101/2021.01.27.428529 33532768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444T NC_045512.2:g.1331A>C YP_009724390.1:p.Lys444Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Results in 3.7-fold drop in neutralization potency for COVA2-29, which is a cluster I RBD141 specific antibody. Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444R NC_045512.2:g.1331A>G YP_009724390.1:p.Lys444Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 20% of supernatant sequences) under two rounds of COV-NY convalescent plasma passage, eliminated in rounds three and four Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444T NC_045512.2:g.1331A>C YP_009724390.1:p.Lys444Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abolishes binding efficiency vs wild type for mAb REGN10933. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects ~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 14% of supernatant sequences) after COV-NY convalescent plasma assay Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Improvement in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-01 and moderately resistant to 2H04 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22896 V445A NC_045512.2:g.1334T>C YP_009724390.1:p.Val445Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 41% appearance in 2 passages against Regeneron monoclonal antibody RGN10987 @ 10ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2499 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 1 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed a ~4x drop in sensitivity. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-02, SARS2-32 and SARS2-35 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Decrease in neutralization capability of all 4 convalescent sera tested (1 ablated). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations), triple replicates. Against a broader panel of 16 convalescent plasma (no replicates), reductions in neutralization are considerably less dramatic in pattern, and sometime neutralization increases. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 95% appearance in 2 passages against Regeneron monoclonal antibody RGN10934 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 4 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Most effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-07 nd moderately resistant to SARS2-16 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910,23012,23039,23040,23373,25046 N450D,N450D,E484K,Q493R,Q493R,T604I,P1162S NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1811C>T,NC_045512.2:g.3484C>T YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Thr604Ile,YP_009724390.1:p.Pro1162Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22905 N448S NC_045512.2:g.1343A>G YP_009724390.1:p.Asn448Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22907 Y449H NC_045512.2:g.1345T>C YP_009724390.1:p.Tyr449His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22907 Y449N NC_045512.2:g.1345T>A YP_009724390.1:p.Tyr449Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912,22916 L452M,L452M NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912,22916 L452M,L452M NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.67 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Observed ~2x decrease on average in neutralization efficacy in convalescent sera of 16 health workers. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 3 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2/3 antibody C628 and class 2 antibody C643 selected for the emergence of the L452R mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021 https://doi.org/10.1101/2021.04.14.21255431 doi:10.1101/2021.04.14.21255431 33907767 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Ablation of neutralization capability of 3 of 4 convalescent sera tested, the other is significantly hindered. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~1.7-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 10 of 14 RBD-specific mAbs that showed at least 10-fold reduced neutralization of B.1.427/B.1.429 variant pseudotype (S13I, W152C, and L452R) were also found to poorly bind to just a L452R RBD mutant, demonstrating a role for this mutation as an escape mechanism for certain RBD-targeting mAbs. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion L452R derivative virus did not induce IFN-gamma expression even at the highest concentration tested (10 nM) in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456). Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects ~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking We observed increased entry by pseudoviruses carrying the L452R mutation compared to D614G alone, with a 6.7 to 22.5-fold increase in 293T cells and a 5.8 to 14.7-fold increase in human airway organoids. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 33758899 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.32 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02. Motozono 2021 https://doi.org/10.1016/j.chom.2021.06.006 doi:10.1016/j.chom.2021.06.006 34171266 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs X593 and P2B-2F6 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. [listed as L454R in Figure, but L452R in text, also text suggests not statistically significant, but error bars say otherwise in Figure 4] Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. L452R conferred about a two-fold reduction in neutralisation by vaccine sera, but was not statistically significant with this sample size. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~5x binding against this isolated mutation. Cligavimab lost ~4x binding against this isolated mutation. Regdanvimab lost ~4x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-02 and SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 33821281 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Increased stability of RBD expression in yeast, suggesting increased Spike protein stability. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012 L452R,L452R,L452R,E484K NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant combination shows a ~4-5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, same as L452R alone. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012 L452R,L452R,L452R,E484Q NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484Q had a ~5x drop in neutralization (vs ~10x for E484K). When E484Q and L452R were combined, the fold change was significant, but similar to that of L452R alone (~2x), suggesting no evidence for an additive effect [perhaps even E484Q effect dilution]. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.617) showed a 1.22x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2.5x. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.617) showed a 1.30x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.18x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x drop in neutralization (NT50) [working with the delins, less than just L452R but more than just E484Q]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x infectivity advantage to the spike particles [less than L452R or E484Q alone working with the delins]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Pseudotyped viruses for B.1.617 was 2.3-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. [details on the convalescent patient sera collection are not abundantly clear in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617) showed a 1.85x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The combination caused a 3-fold increase in infectivity relative to D614G wild type. [compare to 3.5x for L452R alone] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23604 L452R,L452R,L452R,E484Q,P681R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence Gross examination of 3+3 hamster lung specimens showed pronounced congestion and hemorrhages on days 5 and 7 post-infection in the case of the B.1.617.1 as compared with the B.1. The lung lesions with the B.1 variant were minimal to mild whereas with B.1.617.1 they were moderate. For B.1 pneumonic changes were minimal to mild (inflammatory cell infiltration, focal consolidation and mild congestion). The pronounced changes (moderate to severe) with mononuclear infiltration in the alveolar interstitial space, interstitial septal thickening, consolidation and pneumocyte hyperplasia were observed with B.1.617.1 variant consistently. Yadav 2021 https://doi.org/10.1101/2021.05.05.442760 doi:10.1101/2021.05.05.442760 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23604 L452R,L452R,L452R,E484Q,P681R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load In 9 infected hamsters each for B.1 and B.1.617.1, no significant change in viral load or subgenomic RNA levels were detected. Yadav 2021 https://doi.org/10.1101/2021.05.05.442760 doi:10.1101/2021.05.05.442760 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23604 L452R,L452R,L452R,E484K,P681R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant combination shows a ~3x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, significantly less of a decrease than any B.1.617 lineage variants alone, suggesting a synergistic effect on cell entry while maintaining known immunity esacpe mutants. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23604,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,P681R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Normalized for particle number, on ACE2.293T cells showed that the B.1.617 spike protein was >2-fold increase in infectivity relative to D614G wild type. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23060,23061,23062,23063 L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The presence of these B.1.417/B.1.429 defining variants in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021 https://doi.org/10.1101/2021.04.14.21255431 doi:10.1101/2021.04.14.21255431 33907767 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The L452R mutation increased the infectivity more than two-fold in these conditions. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2x. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 7.42x drop in neutralization (NT50) [mostly from 3 of the sera]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this RBD mutation conferred a 2.36x drop in neutralization (NT50). Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~2x infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 583 test-positive were Epsilon. Two dose vaccine efficacy against Epsilon was 97.6 (90.2-99.4%), one dose VE was 76.3 (48.1-89.1%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917 L452Q NC_045512.2:g.1355T>A YP_009724390.1:p.Leu452Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917 L452Q NC_045512.2:g.1355T>A YP_009724390.1:p.Leu452Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.27 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917,23027,23029,23030,23031,23399,23401,23402,23403 L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 3.4x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917,23027,23029,23030,23031,23399,23401,23402,23403 L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.038x fold change in IC50 in C.37 Lambda Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917,23027,23029,23030,23031,23399,23401,23402,23403 L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 1.7x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917,23027,23029,23030,23031,23399,23401,23402,23403 L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.048x fold change in IC50 in C.37 Lambda Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape VSV pseudotyped with Y453F reduced inhibition by most of the 13 potent convalescent serum/plasma samples tested, albeit with variable efficiency (median increase of serum/plasma titer required for 50% neutralization [NT50] = 1.62x, range = 1.02x to 3.43x), indicating that this RBD mutation may compromise SARS-CoV-2 control by preexisting neutralizing antibody responses. Hoffman 2021 https://doi.org/10.1016/j.celrep.2021.109017 doi:10.1016/j.celrep.2021.109017 33857422 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.25 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 10-fold reduction in binding efficiency vs wild type for MAb REGN10933. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~12x binding against this double mutation. Casirivimab lost ~64x binding against this double mutation. Cligavimab lost ~6x binding against this double mutation. Estesevimab lost ~10x binding against this double mutation. Imdevimab lost ~5x binding against this double mutation. Regdanvimab lost ~8x binding against this double mutation. Sotrovimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~4-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed in 4 separate mink farms in Denmark, and Y453F is circulating relatively widely in humans. Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 33172935 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02. Motozono 2021 https://doi.org/10.1016/j.chom.2021.06.006 doi:10.1016/j.chom.2021.06.006 34171266 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion The induction level of IFN-gamma expression by the Y453F derivative in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456) was significantly lower. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 33172935 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Casirivimab lost >50x binding against this mutation. Hoffman 2021 https://doi.org/10.1016/j.celrep.2021.109017 doi:10.1016/j.celrep.2021.109017 33857422 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 Y453F,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.1358A>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence "The so-called ""delta F"" variant combination previously observed in mink spillover events also emerged in a lymphoma patient (non-Hodgkin diffuse B-cell lymphoma IV stage B) with a long-term COVID-19 infection (4 months) where 18 de novo mutation occureed overall. Patient was taking rituximab, the B-cell-depleting agent, and had no detectable neutralizing antibody response." Bazykin 2021 https://virological.org/t/emergence-of-y453f-and-69-70hv-mutations-in-a-lymphoma-patient-with-long-term-covid-19/580 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22924,22925,22926 L455S,L455S,L455S NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.45 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22926,22927,22927,22928,22930,22930 F456L,F456L,F456L,F456L,F456L,F456L NC_045512.2:g.1366T>C,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>A,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>G,NC_045512.2:g.1368T>A YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects This double substitution reduces neutralization by RBD-specific mAbs from different clusters, specifically, the cluster I mAb COVA2-29, cluster III mAb COVA2-07 and cluster VI mAb COVA1-12. For COVA1-12 all neutralization activity is abolished, while COVA2-07 activity is just below the level required to calculate an IC50 value. Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22928 F456V NC_045512.2:g.1366T>G YP_009724390.1:p.Phe456Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22928 F456V NC_045512.2:g.1366T>G YP_009724390.1:p.Phe456Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Moderate in vitro selection against class 1 (Spike 'up' conformation) antibodies C683 and C664. Unclassified antibody C666 selected for the emergence of the F456V mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22928 F456V NC_045512.2:g.1366T>G YP_009724390.1:p.Phe456Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22936 K458N NC_045512.2:g.1374G>T YP_009724390.1:p.Lys458Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.09 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460Y NC_045512.2:g.1378A>T YP_009724390.1:p.Asn460Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460H NC_045512.2:g.1378A>C YP_009724390.1:p.Asn460His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Mild escape mutant emergent for class 1 antibody C613 in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460H NC_045512.2:g.1378A>C YP_009724390.1:p.Asn460His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460H NC_045512.2:g.1378A>C YP_009724390.1:p.Asn460His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22941 N460I NC_045512.2:g.1379A>T YP_009724390.1:p.Asn460Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22941 N460S NC_045512.2:g.1379A>G YP_009724390.1:p.Asn460Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22964 I468V NC_045512.2:g.1402A>G YP_009724390.1:p.Ile468Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22964 I468V NC_045512.2:g.1402A>G YP_009724390.1:p.Ile468Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22976 I472V NC_045512.2:g.1414A>G YP_009724390.1:p.Ile472Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22976 I472V NC_045512.2:g.1414A>G YP_009724390.1:p.Ile472Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to neutralizing mAb X593 (on D614G background) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C102, C105 and C144 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~50x binding against this isolated mutation. Estesevimab lost ~8x binding against this isolated mutation. Sotrovimab lost ~30x binding against this isolated mutation. Tixagevimab lost ~15x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some class 1 (Spike 'up' conformation) antibodies tested. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 host variant dependency This mutation's measured interaction affinity with ACE2:p.S19P (0.03% minor allele frequency, found almost exclusively in African/African-Americans in the GnomAD database) was significantly lower than the predicted value, indicating that these mutations were not independent. This is consistent with the fact that the ACE2 residue S19 is adjacent to RBD residue S477 in the contact interface. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 2.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects While S477N itself is highly resistent to a broad range of monoclonal antibodies, combined with S514F high neutralization is restricted to only three antibodies in a broad screen. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mixed bag of mild positive and negative changes in neutralization capability of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), 10 show low neutralization. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 11 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.22 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-07, SARS2-16 and SARS2-19 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility. Singh 2021 https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows some resistence across all antibodies tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility. Singh 2021 https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding, with increasing proportion in subsequent rounds. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-07 and SARS2-16 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,22995,23042 T478K,T478K,S494P NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1480T>C YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Combination of RBD mutations appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome complicated by diffuse alveolar hemorrhage, who was receiving anticoagulation therapy, glucocorticoids, cyclophosphamide, and intermittent rituximab and eculizumab. Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 33176080 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23012 S477N,E484K NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~10x binding against this double mutation. Tixagevimab lost ~16x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23402,23403 S477N,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was neutralized slightly less than D614G in 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23402,23403 S477N,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23402,23403 S477N,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence Compared to the clade 20A strains that predominated during phase 1 between March and May 2020, the Marseille-4 variant (characterized by this mutation plus N:p.M234I;A376T) was associated with a lower frequency of cough, rhinitis, and olfactory and gustatory disorders. By contrast, hypoxemia was more frequent in patients infected with the Marseille-4 variant. Fournier 2021 https://doi.org/10.1016/j.ijid.2021.03.068 doi:10.1016/j.ijid.2021.03.068 33785459 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23402,23403 S477N,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection "11 cases of re-infection with the ""Marseille-4"" variant found within 1028 positive tests, where all of the earlier infections were from different strains. This lineage is also characterized by N:p.M234I;A376T" Fournier 2021 https://doi.org/10.1016/j.ijid.2021.03.068 doi:10.1016/j.ijid.2021.03.068 33785459 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23003 N481Y NC_045512.2:g.1441A>T YP_009724390.1:p.Asn481Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Minor variant in initial round of in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009 V483L NC_045512.2:g.1447G>C YP_009724390.1:p.Val483Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, 1B07, SARS2-32, SARS2-35 and SARS2-07 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in all 4 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Remarkably, several of the E484 escape mutants were resistant to neutralization at the highest concentration (1:80 initial dilution) of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), all but one show major resistance. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23061,23062,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 152 virus from a chronically infected patient: although mAb C1A-B12 had no activity against this pseudotype, all three affinity optimized versions were active; the antibody containing the most mutations, C1A-B12.3, was the most potent (IC50 <0.5 μg/mL). Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23061,23062,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 152 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 152 S pseudotype was resistant to neutralization. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23061,23062,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This Spike pseudotype for Day 152 virus from a chronically infected patient was completely resistent to REGN10933. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2). Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous. Braeye 2022 https://doi.org/10.1101/2022.05.09.22274623 doi:10.1101/2022.05.09.22274623 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2). Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2). Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness 3rd exposure to antigen by Delta (B.1.617.2) (n=24) breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a 3rd mRNA vaccine dose in individuals aged 21 –63 years, median age=30 years. Data collected 5.5 months after 2nd vaccination. Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous. Braeye 2022 https://doi.org/10.1101/2022.05.09.22274623 doi:10.1101/2022.05.09.22274623 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In sera from 17 sero-positive blood donors, and 18 months post-infection (May 2020) sera from 17 health care workers in Sweden, a 40x drop in neutralization by Omicron (B.1.1.529) pseudotyped lentivirus was observed in HEK293T cells using the First WHO International Standard (20/136). Median IC50 reduction was ~6x for the blood donors, and ~4.5x for the health care workers. Sheward 2021 https://drive.google.com/file/d/1CuxmNYj5cpIuxWXhjjVmuDqntxXwlfXQ/view False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23071,23074,23075,22992,23060,23061,23062,23063 E484A,E484A,E484A,E484A,Y505H,Y505H,Y505H,S477N,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1430G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using molecular dynamics simulation, ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations. Zhang 2022 https://doi.org/10.1101/2022.06.05.493249 doi:10.1101/2022.06.05.493249 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding The only mutation in the B.1.351 lineage that appears to contribute to neutralization reduction (~1.7x across 10 convalescent sera from April 2020 infectees) Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The neutralizing activity of 15/20 convalescent sera was significantly lower against this pseudotyped virus model Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2 antibodies C627, C602, C671, C643, and class 2/3 antibody C603 selected for the emergence of the E484K mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.3x reduction in IC50 serum dilution concentration for 6 convalescent sera." Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 33791698 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers of non-human primate sera after one or two doses of Ad26.COV2.S (Jannsen vaccine) against the variants containing the E484K substitution in the RBD were present but reduced (fold reduction between 3.35–7.78, 95% confidence interval all above twofold difference, one-sample t test). Solfrosi 2021 https://doi.org/10.1084/jem.20202756 doi:10.1084/jem.20202756 33909009 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-02, 1B07, SARS2-16, SARS2-32, SARS2-35 and 2B04 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Multiple individuals in two related households were infected with a newly acquired E484K mutation within the B.1.311 lineage. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient's quarantine period. Sabin 2021 https://doi.org/10.1101/2021.10.02.21264415 doi:10.1101/2021.10.02.21264415 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Of 50 mAbs tested, major loss of neutralization observed for S2N28, S2X615, S2N12, S2X192, S2H7, S2X16, S2X58, S2H70, S2X613, S2D19, S2N22, S2D32, S2H58, S2M11, S2D106, S2X30. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Monoclonal antibodies 13G9 and 58G6 maintain fairly high neutralization potency, compared to others interfacing with E484K. Li 2021 https://doi.org/10.1101/2021.04.19.440481 doi:10.1101/2021.04.19.440481 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Analyzing responses to the E484K mutation seen in B.1.351 and P.1 variants, we noted that it did not fall in a region predicted to bind the HLAII alleles tested (table S4). The mutation appeared to have no substantial or differential impact on T cell responses. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Human sera from 5 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) neutralized this variant 3.4x less relative to reference USA-WA1/2020 strain. 8 convalescent plasma with weak IgG ELISA titre neutralized this variant 2.4x less relative to reference USA-WA1/2020 strain. One plasma failed to neutralize at all. 11 convalescent plasma with moderate IgG ELISA titre neutralized this variant 4.2x less relative to reference USA-WA1/2020 strain. 11 convalescent plasma with high IgG ELISA titre neutralized this variant 2.6x less relative to reference USA-WA1/2020 strain. Jangra 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~20x binding against this isolated mutation. Casirivimab lost ~4x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484K conferred a ten-fold reduction in neutralisation by vaccine sera. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~16x binding against this isolated mutation. Casirivimab lost ~16x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 3 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, E484Q shows a notably resistant profile, comparable to or even more resistant than E484K at later time points (i.e. more resistant to immune cell somatic mutation evolution), see Figure 5a,b. Subject C 32 days post-infection showed >>10 fold reduction in neutralization, reducing to ~10-fold by day 104. Subject B 26 days post-infection showed ~10 fold reduction in neutralization, reducing to ~4x at day 113. Notably, Subject B also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 32, and no E484K immune escape at day 104. Subject I 26 days post-infection showed ~10 fold reduction in neutralization, with no reduction in escape at day 102. Notably, Subject I also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 26, and no E484K immune escape at day 102. Greaney 2021 https://doi.org/10.1016/j.chom.2021.02.003 doi:10.1016/j.chom.2021.02.003 33592168 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in all 4 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Individual variants appearing at <=30% frequency at day 21 in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then appearing all at >95% frequency at day 27. Chen 2021 https://doi.org/10.1101/2021.04.08.21254791 doi:10.1101/2021.04.08.21254791 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.6 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported moderate increase in affinity compared to wild-type RBD on the cell surface (Kd = 38.5nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy E484K pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed a mean 2.8x decrease in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 33851150 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects >20% (ELISA significance threshold) drop in antibody binding by this variant against monoclonal antibody VH-Fc ab8. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant alone shows a 10x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus) Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody VH-Fc ab8 Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus) Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, ELISA tests show 10x reduced efficacy of a majority of isolated antibodies, but only a modest decrease for vaccine plasma overall. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape As measured by surface plasmon resonance, RBD with the E484K mutation alone showed a mean 19.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma. Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape This mutation occurred in 100% of sequenced virions after 12 passages and led to a 4-fold decrease in convalescent plasma neutralization activity Andreano 2020 https://doi.org/10.1101/2020.12.28.424451 doi:10.1101/2020.12.28.424451 33398278 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in binding efficiency vs wild type for mAb LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape due to E484K [given Dec 2020-Apr 2021 time frame of the study, this is assumed to entail both Beta and Gamma lineages]. Chung 2021 https://doi.org/10.1136/bmj.n1943 doi:10.1136/bmj.n1943 34417165 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,22597,22599 E484K,R346K,R346K NC_045512.2:g.1450G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E484K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,22810,22811,22812,22813,22813 E484K,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~32x binding against this double mutation. COR-101 lost ~160x binding against this double mutation. Casirivimab lost ~16x binding against this double mutation. Estesevimab lost ~32x binding against this double mutation. Regdanvimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403 E484K,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~13x more infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,22810,22811,22812,22813,22813,23399,23401,23402,23403 E484K,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Approximately as infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of the individual variants). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23053,23054,23055,23060,23061,23062,23063 E484K,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.4 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.5 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.4 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~17.5x folds more significant in 9 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 35581351 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Values taken 28 days after booster dose was given for BBIBP-CorVvaccine to 390 participants with 130 participants in the 0-14d-10m, 0-21d-10m and 0-28d-10m group. The geometric mean titers (GMT) of neutralizing antibody in 0-28d-10m and 0-21d-10m group were significantly higher than 0-14d-10m group at month 3, month 6 and month 10 after the second dose. A sharply decrease by 4.85-fold (GMT: 94.4-20.3), 4.67-fold (GMT: 134.4-28.8) and 4.49-fold (GMT: 145.5-32.4) was observed from day 28 to month 10 after the second dose in 0-14d-10m, 0-21d-10m and 0-28d-10m group, respectively, and they had similar decline kinetics. Yao T 2022 https://doi.org/10.1101/2022.06.22.22276690 doi:10.1101/2022.06.22.22276690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Omicron neutralizing antibodies is 0.686x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~100x folds more significant in 3 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 35581351 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Viral load from oral swabs from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 35579953 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Viral load from lung tissue from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 35579953 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)] Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)] Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Protection against symptomatic infection caused by Beta/Gamma (assumed by combined presence of N501Y and E484K) was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%). Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Omicron neutralizing antibodies is 0.722x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 20 sera from BNT162b2 mRNA vaccine inoculated participants, 6 displayed mild (2x) reductions in neutralization. This variant combination showed the highest reduction, but the magnitude of the differences was small compared to the >4x differences in HA-inhibition titers that have been used to signal potential need for a strain change in influenza vaccines. Xie 2021 https://doi.org/10.1038/s41591-021-01270-4 doi:10.1038/s41591-021-01270-4 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In the case of VOC B.1.1.7+E484K, the addition of the E484K mutation to N501Y further increased the affinity, to ~15 fold higher than WT RBD (KD ~5 nM), by further increasing the k(on) as measured by surface plasmon resonance. Because the higher k(on) could result in mass transfer limiting binding, we confirmed that the kinetic measurement for this variant was not substantially affected by varying levels of immobilization. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.0015x fold change in IC50 in B.1.1.529 Omicron Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.025x fold change in IC50 in B.1.1.529 Omicron Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 35677079 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Omicron Molnupiravir (MK-4482) had no statistically significant change. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 35579953 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.5 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~11x, Vero ~10x, and Calu-3 ~11x. Compare to wild type at ~5x across cell types. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~12x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of 501 and 484). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~6x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied] Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation ~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Pseudotyped viruses for B.1.618 was 2.5-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. [details on the convalescent patient sera collection are not abundantly clear in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, RBD-specific mutation E484Q did not significantly confer infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 1.34x drop in neutralization (NT50) [mostly from a single serum]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.618 was 2.7-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 3-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~4x infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The estimated vaccine effectiveness against R.1 strain SARS-CoV-2 infection among residents in a Kentucky skilled nursing facility was 66.2% (95% CI = 40.5%–80.8%) and among health care workers was 75.9% (95% CI = 32.5%–91.4%) in the cohort of only those 14d+ post-vaccination Pfizer booster dose. VE against symptomatic COVID-19 was 86.5% (95% CI = 65.6%–94.7%) among residents and 87.1% (95% CI = 46.4%–96.9%) among HCP. VE against hospitalization was 94.4% (95% CI = 73.9%–98.8%) among residents; no HCP were hospitalized. Three residents died, two of whom were unvaccinated (VE = 94.4%; 95% CI = 44.6%–99.4%). Cavanaugh 2021 https://doi.org/10.15585/mmwr.mm7017e2 doi:10.15585/mmwr.mm7017e2 33914720 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403,25088 E484K,D614G,D614G,D614G,D614G,V1176F NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs] Sapkal 2021 https://doi.org/10.1101/2021.04.30.441559 doi:10.1101/2021.04.30.441559 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403,25088 E484K,D614G,D614G,D614G,D614G,V1176F NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs] Sapkal 2021 https://doi.org/10.1101/2021.04.30.441559 doi:10.1101/2021.04.30.441559 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403,25088 E484K,D614G,D614G,D614G,D614G,V1176F NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the P.1 & P.2 lineages of SARS-CoV-2 in Brazil. The Brazilian arm of the Phase 3 double blind study showed severe/critical disease VE of 81.9% (95% CI: 17.0-98.1), and moderate to severe/critical disease VE of 66.2% (95% CI: 51.0-77.1). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 69.3% of mostly severe infections sequenced as of this report, 69.4% were of P.2 lineage [defining lineage SNPs reported here]. 2021 https://www.fda.gov/media/146217/download False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403,25088 E484K,D614G,D614G,D614G,D614G,V1176F NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped P.2 virus has reduced neutralization activity vs wild type: 5.8x (30 sera Pfizer median 9 days post 2nd dose) and 2.9x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23013 E484V NC_045512.2:g.1451A>T YP_009724390.1:p.Glu484Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23013 E484V NC_045512.2:g.1451A>T YP_009724390.1:p.Glu484Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23013 E484V NC_045512.2:g.1451A>T YP_009724390.1:p.Glu484Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486I NC_045512.2:g.1456T>A YP_009724390.1:p.Phe486Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486I NC_045512.2:g.1456T>A YP_009724390.1:p.Phe486Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486I NC_045512.2:g.1456T>A YP_009724390.1:p.Phe486Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2:g.1456T>C YP_009724390.1:p.Phe486Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2:g.1456T>C YP_009724390.1:p.Phe486Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed in 4 separate mink farms in Denmark, but not humans, potential adaptation (diff set of farms than N501T). Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 33172935 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2:g.1456T>C YP_009724390.1:p.Phe486Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutation causes a greater than 100x fold change in IC50 of Ensovibep. Rothenberger 2021 https://doi.org/10.1101/2021.02.03.429164v4 doi:10.1101/2021.02.03.429164v4 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutation causes a greater than 100x fold change in IC50 of Ensovibep. Rothenberger 2021 https://doi.org/10.1101/2021.02.03.429164v4 doi:10.1101/2021.02.03.429164v4 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape IC50 relative to wildtype drops ~8x in neutralization efficiency between 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 1 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects >60% drop in antibody binding (ELISA) by this variant against monoclonal antibody VH-Fc ab8. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 5 antibodies. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.13 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-07, SARS2-19, 1B07, SARS2-16 and 2B04 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed striking resistance with only 38% neutralization at the highest concentration tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Modest decrease in in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23023 N487K NC_045512.2:g.1461T>G YP_009724390.1:p.Asn487Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, high ACE2 binding affinity loss Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Based on structural modelling, this change detected on day 128 sequencing in a chronically infected patient would alter an extensive network of polar interactions with antibody residue R94VH, a germline antibody residue that is conserved in all of the potent VH3-53/3-66-derived antibodies isolated from a convalescent donor 5 weeks after infection. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 33299993 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.11 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-32. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 3 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody ab8 Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 36032981 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2/3 mAb C603 modestly selected for the emergence of this mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (3 ablations). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23060,23061,23062,23063 Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This Spike pseudotype for Day 146 virus from a chronically infected patient was completely resistent to REGN10933. The variant had a 4-fold decrease in REGN10987 neutralization sensitivity (2nd component of the Regeneron mAb cocktail). Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23060,23061,23062,23063 Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 146 virus from a chronically infected patient: resistant to neutralization by mAb C1A-B12, and was still resistant to the affinity enhanced antibodies derived from it (i.e. no affinity maturation effect on neutralization). Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23060,23061,23062,23063 Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 146 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 146 S pseudotype was resistant to neutralization. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 33831372 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490V NC_045512.2:g.1468T>G YP_009724390.1:p.Phe490Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 33259788 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) resistant to 3 individual sera at >4x Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs X593, 261-262, H4, and P2B-2F6 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody ab8 Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Positive selection (up to 23% of supernatant sequences) after C121 monoclonal antibody assay Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in binding efficiency vs wild type for mAbs CB6/LY-CoV16 and LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2 mAb C627 modestly selected for the emergence of this mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 33173867 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Dominant (70%) in day 21 of prolonged infection in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then nearly disappearing (<5%) by day 27. Chen 2021 https://doi.org/10.1101/2021.04.08.21254791 doi:10.1101/2021.04.08.21254791 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 33045718 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 32743579 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 33655250 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 33495307 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 33442690 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 2 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, S484P shows a slightly resistant profile across both timepoints (i.e. resistant to immune cell somatic mutation evolution) Greaney 2021 https://doi.org/10.1016/j.chom.2021.02.003 doi:10.1016/j.chom.2021.02.003 33592168 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-01 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 33535027 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Minor variant selected in late rounds of an in vitro evolution experiment for ACE2 binding. Shown to increase the thermostability but decrease the association rate constant of the RBD to ACE2 Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using molecular dynamic simulation, the mildly (~1kcal/mol) enhanced binding energy of this variant is primarily contributed by Tyr505 (−4.98 kcal/mol) which is now involved in a strong hydrogen bonding network with Arg393. Another important energetic contribution comes from the altered orientation of Tyr41 which is now involved with two hydrogen-bonding interactions with Asp355 and Thr500. 2021 https://doi.org/10.1016/j.bbrc.2021.01.035 doi:10.1016/j.bbrc.2021.01.035 33602511 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Regdanvimab lost ~32x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23048 G496S NC_045512.2:g.1486G>A YP_009724390.1:p.Gly496Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23053,23054,23055,23060,23061,23062,23063 Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. The extent of affinity increase with Q498R and N501Y is not exactly quantified, as E484K always emerged with this duo during in vitro evolution. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 33176080 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~8x binding against this isolated mutation. Regdanvimab lost ~6x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy Variant within the six key residues in the receptor binding domain (RBD). Independently reported in UK, Australia (same origin as UK), and South Africa (independent origin). Flores-Alanis 2021 https://doi.org/10.3390/pathogens10020184 doi:10.3390/pathogens10020184 33572190 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C663, and to a lesser extent C613. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Utilizing shark derived vnarbodies, S375F mutation on Omicron RBD disrupts the structure of β-strand, which inhibits binding with 20G6. 20G6 binds to a hidden epitope on RBD which is highly conserved in sarbecoviruses. Feng 2022 https://doi.org/10.1002/smtd.202200387 doi:10.1002/smtd.202200387 35583124 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 33851185 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.2x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 and day 14 post-2nd dose) against a recombinant single variant virus (modified replicating WA-1 cDNA clone) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 33564782 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.69 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape by lineage Alpha [defined here as N501Y positive, but E484K negative]. Chung 2021 https://doi.org/10.1136/bmj.n1943 doi:10.1136/bmj.n1943 34417165 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In 30 samples collected 111 to 260 days post onset of symptoms, the covalescent plasma can neutralize both the reference USA-WA1/2020 strain and the mouse adapted strain that contains the N501Y spike mutation with similar efficiency. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 33501468 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The N501Y mutation had the biggest effect on ACE2 affinity of any VOC mutation tested, increasing the affinity ~10 fold to KD ~7 nM, by increasing the k(on) ~1.8 fold and decreasing the k(off) by ~ 7 fold as measured by surface plasmon resonance. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 33851185 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021 https://doi.org/10.1101/2021.04.14.21255431 doi:10.1101/2021.04.14.21255431 33907767 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a modest decrease in neutralization by vaccine plasma was observed. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Human sera from 6 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) can neutralize both the reference USA-WA1/2020 strain and the mouse adapted SARS-CoV-2 strain that contains the N501Y spike mutation with similar efficiency. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 33501468 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape As measured by surface plasmon resonance, RBD with the N501Y mutation alone showed a mean 2.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma. Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021 https://doi.org/10.1101/2021.02.02.428884 doi:10.1101/2021.02.02.428884 33564771 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x) Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation alone accounts for most of the increased infectivity of the Alpha variant, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters, and Vero E6 (NHP) and Calu-3 (human) cell lines. Liu 2021 https://doi.org/10.1101/2021.03.08.434499 doi:10.1101/2021.03.08.434499 33758836 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021 https://doi.org/10.1101/2021.02.02.428884 doi:10.1101/2021.02.02.428884 33564771 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021 https://doi.org/10.1101/2021.02.02.428884 doi:10.1101/2021.02.02.428884 33564771 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects "Lowered the neutralization potency of mAb COVA1-12 to the limit of the assay. Decrease in potency was observed against the N501Y pseudotype for the cluster IX mAb COVA2-17." Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Vaccinated, but not post-infection sera, show decreased average T cell response to an N501Y peptide. When we primed transgenic mice expressing human HLA-DRB1*0401 with the Wuhan Hu-1 peptide pool, T cell responses to the B.1.1.7 variant peptide pool were significantly reduced (p = 0.0286). Furthermore, the T cell response to the spike N501Y mutation common to all three of the current VOC was ablated. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~4-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~4-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In silico methods (PyMOL and PDBePISA) involving mutagenesis (N501Y mutation) and interface analysis focusing on the Spike RDB-ACE2 interaction showed that the SARS-CoV-2 N501Y mutant (lineage B.1.1.7) establishes a more significant number of interactions relating to the mutant residue Y501 (Spike RDB) with residues Y41 and K353 (ACE2). This finding shows that the increased infectivity of SARS-CoV-2 lineage B.1.1.7 is associated with the interaction force between the Spike RBD Y501 mutant residue with the ACE2 receptor, which in this strain is increased. 2021 https://doi.org/10.1101/2020.12.29.424708 doi:10.1101/2020.12.29.424708 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Of 50 mAbs tested, major loss of neutralization observed for S2X128, S2D8, S2X192, S2D19, S2H14, S2H19. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x) Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 33532764 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 33501451 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Contrary to other reports on N501Y containing lineages (i.e. with additional mutations), N501Y alone may have an even greater affinity for a human monoclonal antibody specific for wild type. These results suggest that the individual N501Y mutation does not contribute to altered viral properties by itself, but may contribute to a collective conformational shift produced by multiple mutations. Klegerman 2021 https://doi.org/10.1101/2021.04.26.441517 doi:10.1101/2021.04.26.441517 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity. Zhu 2021 https://doi.org/10.1101/2021.01.11.426269 doi:10.1101/2021.01.11.426269 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021 https://doi.org/10.1101/2021.02.02.428884 doi:10.1101/2021.02.02.428884 33564771 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity. Zhu 2021 https://doi.org/10.1101/2021.01.11.426269 doi:10.1101/2021.01.11.426269 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021 https://doi.org/10.1101/2021.02.02.428884 doi:10.1101/2021.02.02.428884 33564771 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM). Ramanathan 2021 https://doi.org/10.1101/2021.02.22.432359 doi:10.1101/2021.02.22.432359 33655251 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM). Ramanathan 2021 https://doi.org/10.1101/2021.02.22.432359 doi:10.1101/2021.02.22.432359 33655251 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slightly increased infection rate amongst the cells. [in what is essentially a replicate experiment in the same paper, because each B.1.351 lineage variant was independetly evaluated and N501 is in both lineages, a significant decrease was observed, therefore the error bars described in this paper should be interpreted carefully] Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The most frequent RBM mutation N501Y (165,519 instances) makes defective the atypical N-glycosylation sequon NGV 501-503, becoming a key RBM position for the interaction with hACE2-binding hotspot 353. Gamez 2021 https://doi.org/10.1101/2021.04.09.439154 doi:10.1101/2021.04.09.439154 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape 0.7x reduction in neutralization by key variant in several variants of concern in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity. Zhu 2021 https://doi.org/10.1101/2021.01.11.426269 doi:10.1101/2021.01.11.426269 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,22810,22811,22812,22813,22813 N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~20x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~6x binding against this double mutation. M396 lost ~10x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,22810,22811,22812,22813,22813,23012 N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In post-vaccination sera from individuals who received one (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) of the BNT162b2 Pfizer vaccine, an average 6.8x reduction in neutralization efficacy of this B.1.351 key variants pseudotype lentivirus vs D614G was observed. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,22810,22811,22812,22813,22813,23012 N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape ~7x reduction in neutralization by key B.1.351 lineage RBD variant combination in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Two of the cohort showed no neutralization against this variant. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23012 N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~64x binding against this double mutation. COR-101 lost ~50x binding against this double mutation. Casirivimab lost ~250x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~32x binding against this double mutation. Tixagevimab lost ~10x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23271 N501Y,N501Y,N501Y,N501Y,A570D NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Partial sequencing of S gene reveals two cases of probable early 2021 B.1.1.7 lineage reinfection from non-B.1.1.7 original cases in Lombardy, with 45 to 90 days between infections (less than the typical 90 day guideline for this call). Patients were 56 and 58yo, immunocompenent, with one a former smoker with obesity and dyslipidemia. One case required intubation during first infection, but presented with mild symptoms upon reinfection. The other case convalesced at home during the first episode, but required CPAP support in the subacute clinical unit upon reinfection. Novazzi 2021 https://doi.org/10.1002/jmv.27066 doi:10.1002/jmv.27066 33969504 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation ~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~9x, Vero ~8x, and Calu-3 ~8x. Compare to wild type at ~5x across cell types. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~13x, Vero ~10x, and Calu-3 ~10x. Compare to wild type at ~5x across cell types. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking 9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking 9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed no change in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding "Lentiviral pseudotyped with the key mutations from COH.20G/677H (""Ohio"") lineage was neutralized similarly to D614G in 10 convalescent sera from April 2020 infectees." Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells for ACE2 affinity changes vs D614G alone, showing a ~70% drop in IC50 (i.e. increased affinity). Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23521,23522,23524,23525 N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 33501468 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23071,23074,23075 Y505H,Y505H,Y505H NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed first in a single tiger (cohort of 5), potential adaptation. McAloose 2020 https://doi.org/10.1128/mBio.02220-20 doi:10.1128/mBio.02220-20 33051368 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23071,23074,23075 Y505H,Y505H,Y505H NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23102 S514T NC_045512.2:g.1540T>A YP_009724390.1:p.Ser514Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23108 E516Q NC_045512.2:g.1546G>C YP_009724390.1:p.Glu516Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23115 L518Q NC_045512.2:g.1553T>A YP_009724390.1:p.Leu518Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23120 A520S NC_045512.2:g.1558G>T YP_009724390.1:p.Ala520Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness CR3022 (SARS-targeting mAb) cross-reactivity lost ~4x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23148 K529T NC_045512.2:g.1586A>C YP_009724390.1:p.Lys529Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.15 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 32841599 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing statistically significant increased infection rate amongst the cells. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated that there is very little free energy change (ddG. -0.02 kcal/mol) for this variant (i.e. approx. same stability as wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant raises PIWAS epitope score from 3.6% to 6.2% (improved immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23373 T604I NC_045512.2:g.1811C>T YP_009724390.1:p.Thr604Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a lentivirus virus pseudotyped with D614G Spike, sera from vaccinated individuals who received the second dose (9–11 days post-second dose of Pfizer) exhibited a robust neutralizing potential, with a mean NT50 value of 99,000. This was an average of a 2-fold increase, relative to sera drawn from the individuals who received one dose of vaccination—mean NT50 dilution of 51,300. Importantly, a 6-fold increase in mean NT50 dilution was obtained when sera from the first vaccination dose was compared to convalescent sera from cohort with severe disease (NT50 51,000 vs 8,700) 21 to 63 days post-onset. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 33789085 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 2.5 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to wild type, D614G showed increased infectivity (ie. cold stability) after storage at -20°C for up to 30 days. Huang 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped D614G virus has reduced neutralization activity vs wild type: 1.2x (37 sera Pfizer median 9 days post 2nd dose, 37 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 33743213 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.05x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.45x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.43x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 1.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In four cell lines (including 293T-hACE2 cells), this mutation combination increases infectivity vs D614G alone Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Yurkovetskiy 2020 https://doi.org/10.1016/j.cell.2020.09.032 doi:10.1016/j.cell.2020.09.032 32991842 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events "This mutation (a.k.a. ""Doug"") outside the receptor binding domain, while highly favorable to improved human-human transmission, decreases transduction in naked mole-rat (Heterocephalus glaber) fibroblast and Japanese pipistrelle bat (Pipistrellus abramus) cell cultures using a pseudotyped VSV assay." Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Weissman 2020 https://doi.org/10.1101/2020.07.22.20159905 doi:10.1101/2020.07.22.20159905 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 conferred a nearly two-fold infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD mutation conferred a 4.85x drop in neutralization (NT50). Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Yurkovetskiy 2020 https://doi.org/10.1016/j.cell.2020.09.032 doi:10.1016/j.cell.2020.09.032 32991842 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Weissman 2020 https://doi.org/10.1101/2020.07.22.20159905 doi:10.1101/2020.07.22.20159905 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." Yurkovetskiy 2020 https://doi.org/10.1016/j.cell.2020.09.032 doi:10.1016/j.cell.2020.09.032 32991842 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.35x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission. Plante 2020 https://doi.org/10.1038/s41586-020-2895-3 doi:10.1038/s41586-020-2895-3 33106671 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 33917138 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses. Ozono 2020 https://doi.org/10.1038/s41467-021-21118-2 doi:10.1038/s41467-021-21118-2 33558493 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses. Ozono 2020 https://doi.org/10.1038/s41467-021-21118-2 doi:10.1038/s41467-021-21118-2 33558493 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Studying 94 COVID-19 extended infection cases with genomics April 1 to October 17, 2020, one case developed 23 mutations in a 19 day period, including this combination in Spike. Landis 2021 https://doi.org/10.1101/2021.05.08.21256775 doi:10.1101/2021.05.08.21256775 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking The increased transduction with Spike D614G ranged from 1.3- to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2 and from 1.5- to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction. Daniloski 2021 https://doi.org/10.7554/eLife.65365 doi:10.7554/eLife.65365 33570490 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.97x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a slight decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.53x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 33243994 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575 D614G,D614G,D614G,D614G,L5F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.1x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575 D614G,D614G,D614G,D614G,L5F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.23x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575 D614G,D614G,D614G,D614G,L5F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664 D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.526) showed a 1.02x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664 D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.526) showed a 1.78x increase in binding (KD) relative to D614G, even though each variant independently decreases binding. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664 D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.526) showed a 1.34x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600 D614G,D614G,D614G,D614G,S13I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600 D614G,D614G,D614G,D614G,S13I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.42x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600 D614G,D614G,D614G,D614G,S13I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600,22018,22915,22916,22917 D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. [Stark contrast to 2.15x increase in binding by convalescent plasma 8 months post infection, presumably via memory B cell affinity maturation against L452R effects] 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600,22018,22915,22916,22917 D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.429 aka Epsilon) showed a 2.82x increase in binding (KD) relative to D614G, indicating a strong marginal effect for L452R. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600,22018,22915,22916,22917 D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, indicating ablated marginal effect from L452R. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614 D614G,D614G,D614G,D614G,L18F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.07x decrease in binding (KD) relative to D614G. Compare to increased binding in full Spike variant complements for major lineages containing this variant subset: 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614 D614G,D614G,D614G,D614G,L18F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.66x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Compare to decreased binding in full Spike variant complements for major lineages containing this variant subset: 0.96x (B.1.351 aka Beta), 0.77x (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614 D614G,D614G,D614G,D614G,L18F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.30x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.28x increase (B.1.351 aka Beta), and 1.14x decrease (P.1 aka Gamma). 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.17x increase (B.1.351 aka Beta), and 1.47x decrease (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing P.1 aka Gamma) showed a 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing P.1 aka Gamma) showed a 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing P.1 aka Gamma) showed a 4.24x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664 D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing B.1.351 aka Beta) showed a 1.04x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, in contrast to the largely positive binding values for each individual mutation that comprises the set. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664 D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing B.1.351 aka Beta) showed a 1.28x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. It shows a 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664 D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.351 aka Beta) showed a 3.56x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21621 D614G,D614G,D614G,D614G,T20N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.39x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21621 D614G,D614G,D614G,D614G,T20N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.96x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21621 D614G,D614G,D614G,D614G,T20N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21638 D614G,D614G,D614G,D614G,P26S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.58x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21638 D614G,D614G,D614G,D614G,P26S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.23x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21638 D614G,D614G,D614G,D614G,P26S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.33x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.51x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing B.1.1.7 aka Alpha) showed no change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.28x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing B.1.1.7 aka Alpha) showed a 1.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.1.7 aka Alpha) had 5.43x increased binding relative to D614G alone. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21801 D614G,D614G,D614G,D614G,D80A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination showed no change relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21801 D614G,D614G,D614G,D614G,D80A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.64x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.35x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21801 D614G,D614G,D614G,D614G,D80A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21846 D614G,D614G,D614G,D614G,T95I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21846 D614G,D614G,D614G,D614G,T95I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21846 D614G,D614G,D614G,D614G,T95I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21974 D614G,D614G,D614G,D614G,D138Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21974 D614G,D614G,D614G,D614G,D138Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21974 D614G,D614G,D614G,D614G,D138Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.32x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22018 D614G,D614G,D614G,D614G,W152C NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.15x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22018 D614G,D614G,D614G,D614G,W152C NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22018 D614G,D614G,D614G,D614G,W152C NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.03x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22132 D614G,D614G,D614G,D614G,R190S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.59x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22132 D614G,D614G,D614G,D614G,R190S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.82x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22132 D614G,D614G,D614G,D614G,R190S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22206 D614G,D614G,D614G,D614G,D215G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.19x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22206 D614G,D614G,D614G,D614G,D215G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.79x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22206 D614G,D614G,D614G,D614G,D215G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D253G,D253G,D253G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D253G,D253G,D253G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.08x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D253G,D253G,D253G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22810,22811,22812,22813,22813 D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22810,22811,22812,22813,22813 D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.76x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.75x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22810,22811,22812,22813,22813 D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22812 D614G,D614G,D614G,D614G,K417T NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.28x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22812 D614G,D614G,D614G,D614G,K417T NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22812 D614G,D614G,D614G,D614G,K417T NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.66x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.05x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.16x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 6.2-fold lower (95% CI: 11.8x-14.3x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 4.2x-fold lower (95% CI: 0.15x-0.20x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy paired testing of vaccine sera against ancestral virus compared to Omicron BA.1 shows that 3-dose vaccine regimen provides over 50x fold increase in protection against Omicron(B.1.1.529 [BA.1]) compared to a 2-dose regimen. Hao 2022 https://doi.org/10.1101/2022.08.12.22278720 doi:10.1101/2022.08.12.22278720 36032965 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 28.7x-fold lower (95% CI: 0.03x-0.05) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness 4th antigenic exposure with Omicron (B.1.1.529 [BA.1])(n=29) infection increased variant specific plasma antibody and memory B cell responses as well as overall increased strain specific memory in individuals aged 22 –79 years, median age=33.5 years. Data collected 2.4 months after 3rd vaccination. Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 3.4-fold lower (95% CI: 3.2x-3.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 3.9x-fold lower (95% CI: 0.14x-0.17x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 78fM for binding to the Omicron BA.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 4.5-fold lower (95% CI: 4.3x-4.7x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 4.2-fold lower (95% CI: 5.8x-6.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 3.9x-fold lower (95% CI: 0.14x-0.18x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23012 D614G,D614G,D614G,D614G,E484K NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.42x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23012 D614G,D614G,D614G,D614G,E484K NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23012 D614G,D614G,D614G,D614G,E484K NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This variant appears twice in the experiments, with slightly different affinities (both ~1.2x decrease in binding relative to D614G) using flow cytometry and ACE2 ectodomains-Fc portion IgG complex. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23060,23061,23062,23063 D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23060,23061,23062,23063 D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23060,23061,23062,23063 D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.52x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis). Compare to full Spike variant complements for major lineages containing this variant subset: 5.43x (B.1.1.7 aka Alpha), 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23271 D614G,D614G,D614G,D614G,A570D NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23271 D614G,D614G,D614G,D614G,A570D NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23271 D614G,D614G,D614G,D614G,A570D NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.18x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23521,23522,23524,23525 D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23521,23522,23524,23525 D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.21x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23521,23522,23524,23525 D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.48x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23604 D614G,D614G,D614G,D614G,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant change in virus neutralzation by 18 Pfizer two dose vaccinee sera compared to B.1.1.7. [results without including the used mutation A27S likely generalizable, as this is not a lineage defining mutation] Zuckerman 2021 https://doi.org/10.1101/2021.03.25.21253908 doi:10.1101/2021.03.25.21253908 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23604 D614G,D614G,D614G,D614G,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.26x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23604 D614G,D614G,D614G,D614G,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23604 D614G,D614G,D614G,D614G,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23664 D614G,D614G,D614G,D614G,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23664 D614G,D614G,D614G,D614G,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23664 D614G,D614G,D614G,D614G,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed essentially no change in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23709 D614G,D614G,D614G,D614G,T716I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.12x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23709 D614G,D614G,D614G,D614G,T716I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23709 D614G,D614G,D614G,D614G,T716I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.58x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24506 D614G,D614G,D614G,D614G,S982A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24506 D614G,D614G,D614G,D614G,S982A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.3x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24506 D614G,D614G,D614G,D614G,S982A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24642 D614G,D614G,D614G,D614G,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.69x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24642 D614G,D614G,D614G,D614G,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.22x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24642 D614G,D614G,D614G,D614G,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.56x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24914 D614G,D614G,D614G,D614G,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24914 D614G,D614G,D614G,D614G,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24914 D614G,D614G,D614G,D614G,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.96x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23429 A623T NC_045512.2:g.1867G>A YP_009724390.1:p.Ala623Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23522,23524,23525 H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23522,23524,23525 H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain increases the virus transduction rate in tree shrew (Tupaia belangeri), (as it does in humans) according to pseudotyped VSV experiments. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23522,23524,23525 H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.87 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23522,23524,23525 H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Six minks were intranasally infected with WA1 isolate, all developed this mutation during infection. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23587,23587 Q675H,Q675H NC_045512.2:g.2025G>C,NC_045512.2:g.2025G>T YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly enhanced the ability of the pseudotyped VSV to infect fat-tailed gerbil (Pachyuromys duprasi) kidney cell cultures, with a transduction rate of 13.4%, close to the 15.7% in epithelial-like human Huh-7 cells while starting from a significantly lower wildtype (Wuhan-Hu-1 Spike VSVdeltaG psuedotype) rate. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681R NC_045512.2:g.2042C>G YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. [PG: Inferred by conservative AA substitution of described P681H] Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic. Johnson 2020 https://doi.org/10.1101/2020.08.26.268854 doi:10.1101/2020.08.26.268854 32869021 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In the absence of N501Y, this Alpha lineage change in the furin clevage site did NOT show significant increase in infectivity relative to wild type, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters. Liu 2021 https://doi.org/10.1101/2021.03.08.434499 doi:10.1101/2021.03.08.434499 33758836 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). 2021 https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). 2021 https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing NO statistically significant infection rate change amongst the cells, suggesting that furin cleavage typically used for cell entry is not affected by this change one amino acid upstream of the RXXR recognition pattern. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 0.9x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic. Johnson 2020 https://doi.org/10.1101/2020.08.26.268854 doi:10.1101/2020.08.26.268854 32869021 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w 33664494 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681R NC_045512.2:g.2042C>G YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). [Inference from similar positively charged substitution P681H actually described in the work] 2021 https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking While the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC). Lubinski 2021 https://doi.org/10.1101/2021.04.06.438731 doi:10.1101/2021.04.06.438731 33851153 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23399,23401,23402,23403 P681R,D614G,D614G,D614G,D614G NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Quantification of the band intensities showed that the P681R mutation, which lies near the proteolytic processing site, caused a small increase in proteolytic processing as measured by a 2-fold decrease in the ratio of S/S2. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23664 A701V NC_045512.2:g.2102C>T YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23664 A701V NC_045512.2:g.2102C>T YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.33 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not in a major wildtype epitope, mutant increases PIWAS epitope score from 0.69% to 2.3% Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain showed a decreased capacity to transduce PK-15 (pig kidney, Sus scrofa) and PaKi (black flying fox kidney, Pteropus alecto) cell line cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed first in a single tiger (cohort of 5), potential adaptation. McAloose 2020 https://doi.org/10.1128/mBio.02220-20 doi:10.1128/mBio.02220-20 33051368 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. T716I was expressed at significantly lower level, accounting for the decreased infectivity of this spike protein. This property may be specific to spike protein biosynthesis in 293T cells and is not likely to reflect the situation in vivo given the reported increase in infectivity of the B.1.1.7 virus. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23897 Q779K NC_045512.2:g.2335C>A YP_009724390.1:p.Gln779Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 20% appearance in 2 passages against Regeneron monoclonal antibody RGN10989 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 32540904 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23948 D796H NC_045512.2:g.2386G>C YP_009724390.1:p.Asp796His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Fatal COVID-19 complications in immunocomprimised patient after immune escape from convalescent plasma Kemp 2020 https://doi.org/10.1101/2020.12.05.20241927 doi:10.1101/2020.12.05.20241927 33398302 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24000 S813I NC_045512.2:g.2438G>T YP_009724390.1:p.Ser813Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2:g.2492C>T YP_009724390.1:p.Ala831Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to neutralizing mAb B38 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2:g.2492C>T YP_009724390.1:p.Ala831Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2:g.2492C>T YP_009724390.1:p.Ala831Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 32730807 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24077 D839N NC_045512.2:g.2515G>A YP_009724390.1:p.Asp839Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry. Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24077 D839Y NC_045512.2:g.2515G>T YP_009724390.1:p.Asp839Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry. Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24130 N856K NC_045512.2:g.2568C>A YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. Lucaci 2021 Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24170 I870V NC_045512.2:g.2608A>G YP_009724390.1:p.Ile870Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Appeared at same time as T478K,S494P but listed separately due to distance and different domains affected in the Spike (i.e. putatively an independent mutation from a functional standpoint since the former are from S1, the latter from S2). Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 33176080 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24377,24378 S939F,S939F NC_045512.2:g.2816C>T,NC_045512.2:g.2816C>T YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 36690780 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The neutralizing activity of 6/20 convalescent sera was significantly lower against this single variant pseudotyped virus model, showing similar patterns to the pseudotyped virus model of B.1.1.7. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (70%) increase in infection rate amongst the cells, hence this individual variant is likely to significantly contribute to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24642 T1027I NC_045512.2:g.3080C>T YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 1.51 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 33791700 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Mutation is predicted to lose the T cell epitope for people carrying DRB1*0301 and DRB1*0401, but not for example in those who are DRB1*0701 or DRB1*1501 who would be predicted to show an enhanced response. This is also observed in a study of 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 33931567 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25046 P1162S NC_045512.2:g.3484C>T YP_009724390.1:p.Pro1162Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25249,25249,25249 M1229I,M1229I,M1229I NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 33564768 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25350 P1263L NC_045512.2:g.3788C>T YP_009724390.1:p.Pro1263Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant in the cytoplasmic tail, shown in vitro to increase Spike subunit fusion required for cell entry Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 33532777 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25855 D155Y NC_045512.2:g.463G>T YP_009724391.1:p.Asp155Tyr open reading frame 3a gene (SARS-CoV-2) orf3a gene (SARS-CoV-2) open reading frame 3a protein (SARS-CoV-2) Orf3a protein (SARS-CoV-2) caveolin binding In silico, this mutation is the only one weakening ORF3a's binding affinity for caveolin-1 (essential for entry and endomembrane trafficking of SARS-CoV-2). This mutation is a widespread homoplasy in 20A and 20B lineages. Gupta 2021 https://doi.org/10.1101/2021.03.26.437194 doi:10.1101/2021.03.26.437194 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26029 Q213K NC_045512.2:g.637C>A YP_009724391.1:p.Gln213Lys open reading frame 3a gene (SARS-CoV-2) orf3a gene (SARS-CoV-2) open reading frame 3a protein (SARS-CoV-2) Orf3a protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*01:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26029 Q213K NC_045512.2:g.637C>A YP_009724391.1:p.Gln213Lys open reading frame 3a gene (SARS-CoV-2) orf3a gene (SARS-CoV-2) open reading frame 3a protein (SARS-CoV-2) Orf3a protein (SARS-CoV-2) T cell evasion "Variant causes complete loss of T cell line responsiveness to A*01:01-restricted CD8+ ORF3a epitope, which is otherwise ""consistently dominant and of high magnitude""." de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26256 F4F NC_045512.2:g.12C>T YP_009724392.1:p.Phe4Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26268,26269,26270 T9I,T9I,T9I NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~300 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26268,26269,26270 T9I,T9I,T9I NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26296 L18I NC_045512.2:g.52C>A YP_009724392.1:p.Leu18Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (47x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26299 L19F NC_045512.2:g.55C>T YP_009724392.1:p.Leu19Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26312 F23C NC_045512.2:g.68T>G YP_009724392.1:p.Phe23Cys envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~8.8 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26314 V24M NC_045512.2:g.70G>A YP_009724392.1:p.Val24Met envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26319 V25V NC_045512.2:g.75A>G YP_009724392.1:p.Val25Val envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (45x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26333 T30I NC_045512.2:g.89C>T YP_009724392.1:p.Thr30Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26353 L37F NC_045512.2:g.109C>T YP_009724392.1:p.Leu37Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26395 L51I NC_045512.2:g.151C>A YP_009724392.1:p.Leu51Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (47x overrepresentation vs expected count of ~24 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26416 V58L NC_045512.2:g.172G>C YP_009724392.1:p.Val58Leu envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26428 V62F NC_045512.2:g.184G>T YP_009724392.1:p.Val62Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (18x overrepresentation vs expected count of ~333 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26442 N66K NC_045512.2:g.198T>G YP_009724392.1:p.Asn66Lys envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~23 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26447 S68F NC_045512.2:g.203C>T YP_009724392.1:p.Ser68Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26447 S68C NC_045512.2:g.203C>G YP_009724392.1:p.Ser68Cys envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (58x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26456 P71R NC_045512.2:g.212C>G YP_009724392.1:p.Pro71Arg envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26467 V75L NC_045512.2:g.223G>C YP_009724392.1:p.Val75Leu envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (3762.7x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526 A2S NC_045512.2:g.4G>T YP_009724393.1:p.Ala2Ser membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) immunosuppression variant emergence Emergent as 16% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing. Avanzato 2020 https://doi.org/10.1016/j.cell.2020.10.049 doi:10.1016/j.cell.2020.10.049 33248470 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526 A2S NC_045512.2:g.4G>T YP_009724393.1:p.Ala2Ser membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (38x overrepresentation vs expected count of ~334 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526,26527,26529 D3H,D3H,D3H NC_045512.2:g.7G>C,NC_045512.2:g.7G>C,NC_045512.2:g.7G>C YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (227x overrepresentation vs expected count of ~14 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26528,26528,26528 A2A,A2A,A2A NC_045512.2:g.6A>T,NC_045512.2:g.6A>G,NC_045512.2:g.6A>C YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (25x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26530 D3G NC_045512.2:g.8A>G YP_009724393.1:p.Asp3Gly membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (31x overrepresentation vs expected count of ~53 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26542 T7I NC_045512.2:g.20C>T YP_009724393.1:p.Thr7Ile membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 33501468 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26546 I8I NC_045512.2:g.24T>C YP_009724393.1:p.Ile8Ile membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~80 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26573,26576,26577 Q19E,Q19E,Q19E NC_045512.2:g.55C>G,NC_045512.2:g.55C>G,NC_045512.2:g.55C>G YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~8 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26620 C33S NC_045512.2:g.98G>C YP_009724393.1:p.Cys33Ser membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~32 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26645 N41N NC_045512.2:g.123C>T YP_009724393.1:p.Asn41Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (19x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26681 F53F NC_045512.2:g.159C>T YP_009724393.1:p.Phe53Phe membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (163x overrepresentation vs expected count of ~567 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26730 V70L NC_045512.2:g.208G>C YP_009724393.1:p.Val70Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26748 I76V NC_045512.2:g.226A>G YP_009724393.1:p.Ile76Val membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26748 I76L NC_045512.2:g.226A>C YP_009724393.1:p.Ile76Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~9 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26749 I76T NC_045512.2:g.227T>C YP_009724393.1:p.Ile76Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (19x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26767 I82T NC_045512.2:g.245T>C YP_009724393.1:p.Ile82Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) homoplasy This mutation presents mainly within the B.1 (44.0%) and B.1.525 (38.1%) lineages. Currently, 99.7% of the B.1.525 lineage isolates carry the M:I82T mutation. While this mutation is scattered across multiple phylogenetic clades, most cases cluster in two recent clades, suggesting a likely selective advantage in certain haplotype backgrounds. Shen 2021 https://doi.org/10.1080/22221751.2021.1922097 doi:10.1080/22221751.2021.1922097 33896413 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26767 I82T NC_045512.2:g.245T>C YP_009724393.1:p.Ile82Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (67x overrepresentation vs expected count of ~42 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26801,26801,26801 L93L,L93L,L93L NC_045512.2:g.279C>G,NC_045512.2:g.279C>A,NC_045512.2:g.279C>T YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~628 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26855,26858 F112F,F112F NC_045512.2:g.336C>T,NC_045512.2:g.336C>T YP_009724393.1:p.Phe112Phe,YP_009724393.1:p.Phe112Phe membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~463 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26861 N113N NC_045512.2:g.339T>C YP_009724393.1:p.Asn113Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (57x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26873 N117N NC_045512.2:g.351C>T YP_009724393.1:p.Asn117Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26882,26882 L120L,L120L NC_045512.2:g.360C>A,NC_045512.2:g.360C>T YP_009724393.1:p.Leu120Leu,YP_009724393.1:p.Leu120Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26894,26894 L124L,L124L NC_045512.2:g.372C>T,NC_045512.2:g.372C>G YP_009724393.1:p.Leu124Leu,YP_009724393.1:p.Leu124Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26895 H125Y NC_045512.2:g.373C>T YP_009724393.1:p.His125Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (22x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26895 H125Y NC_045512.2:g.373C>T YP_009724393.1:p.His125Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) homoplasy In experimental models of SARA_CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26907,26909,26909 L129L,L129L,L129L NC_045512.2:g.385C>T,NC_045512.2:g.387G>A,NC_045512.2:g.387G>T YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26927 E135E NC_045512.2:g.405A>G YP_009724393.1:p.Glu135Glu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (232x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26951,26951,26951 V143V,V143V,V143V NC_045512.2:g.429G>C,NC_045512.2:g.429G>A,NC_045512.2:g.429G>T YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~508 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26966 H148H NC_045512.2:g.444T>C YP_009724393.1:p.His148His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26972 R150R NC_045512.2:g.450T>C YP_009724393.1:p.Arg150Arg membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~89 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26985 H155N NC_045512.2:g.463C>A YP_009724393.1:p.His155Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26987 H155H NC_045512.2:g.465T>C YP_009724393.1:p.His155His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27021 E167Q NC_045512.2:g.499G>C YP_009724393.1:p.Glu167Gln membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27035,27038 T172T,T172T NC_045512.2:g.516A>G,NC_045512.2:g.516A>G YP_009724393.1:p.Thr172Thr,YP_009724393.1:p.Thr172Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27059 Y179Y NC_045512.2:g.537C>T YP_009724393.1:p.Tyr179Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27112 S197T NC_045512.2:g.590G>C YP_009724393.1:p.Ser197Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (18x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27134 Y204Y NC_045512.2:g.612T>C YP_009724393.1:p.Tyr204Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27143 N207N NC_045512.2:g.621C>T YP_009724393.1:p.Asn207Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27147 D209H NC_045512.2:g.625G>C YP_009724393.1:p.Asp209His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (81x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27367 Q56X NC_045512.2:g.166C>T YP_009724394.1:p.Gln56Xaa open reading frame 6 gene (SARS-CoV-2) orf6 gene (SARS-CoV-2) open reading frame 6 protein (SARS-CoV-2) Orf6 protein (SARS-CoV-2) IFN activity The residues listed are determinants of the potent IFN-antagonistic activity of SARS-CoV-2 ORF6 (via blocking mRNA nuclear export) Kimura 2020 https://doi.org/10.2139/ssrn.3690468 doi:10.2139/ssrn.3690468 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28144 L84S NC_045512.2:g.251T>C YP_009724396.1:p.Leu84Ser open reading frame 8 gene (SARS-CoV-2) orf8 gene (SARS-CoV-2) open reading frame 8 protein (SARS-CoV-2) Orf8 protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 33501468 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28307,28309,28310,28311 P13L,P13L,P13L,P13L NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28307,28309,28310,28311 P13L,P13L,P13L,P13L NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13). de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28310 P13S NC_045512.2:g.37C>T YP_009724397.2:p.Pro13Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13). de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28310 P13S NC_045512.2:g.37C>T YP_009724397.2:p.Pro13Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*27:05. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28769 T166A NC_045512.2:g.496A>G YP_009724397.2:p.Thr166Ala nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) variant linear antibody epitope effects Confers a significant PIWAS value decrease (reduced antigenicity) Haynes 2020 https://doi.org/10.1101/2020.11.23.20235002 doi:10.1101/2020.11.23.20235002 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28853 S194T NC_045512.2:g.580T>A YP_009724397.2:p.Ser194Thr nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 33501468 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28854 S194L NC_045512.2:g.581C>T YP_009724397.2:p.Ser194Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) homoplasy Mutation with a population frequency of 30% in a Mexican dataset, primarily of lineage 20B, but also present in a substantial number of 20A lineage sequences, suggesting convergent evolution. Barona-Gomez 2021 https://doi.org/10.1101/2021.05.18.21256128 doi:10.1101/2021.05.18.21256128 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28854 S194L NC_045512.2:g.581C>T YP_009724397.2:p.Ser194Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) outcome hazard ratio In March 2021 this variant had an allele frequency of 47.62 and 7.25% in deceased patients, compared to 35.16 and 3.20% of the same variant in recovered patients, from the Gujarat and global datasets. Joshi 2021 https://doi.org/10.3389/fgene.2021.586569 doi:10.3389/fgene.2021.586569 33815459 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28869 P199L NC_045512.2:g.596C>T YP_009724397.2:p.Pro199Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021 https://doi.org/10.1101/2021.08.05.455082 doi:10.1101/2021.08.05.455082 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28879 S202R NC_045512.2:g.606T>G YP_009724397.2:p.Ser202Arg nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows major increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021 https://doi.org/10.1101/2021.08.05.455082 doi:10.1101/2021.08.05.455082 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28881 R203M NC_045512.2:g.608G>T YP_009724397.2:p.Arg203Met nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows most increase in RNA content of any N mutation tested, suggesting that this mutation improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021 https://doi.org/10.1101/2021.08.05.455082 doi:10.1101/2021.08.05.455082 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28977 S235F NC_045512.2:g.704C>T YP_009724397.2:p.Ser235Phe nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) variant linear antibody epitope effects Substantially increases epitope and antigen scores in 2 of 579 individuals (should increase immune response). In the B1.1.7 lineage this is largely counteracted by the D3L mutation, which decreases PIWAS signal significantly in 1.5% of COVID patients, for a net neutral effect at the population level. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29239,29239 M322I,M322I NC_045512.2:g.966G>A,NC_045512.2:g.966G>T YP_009724397.2:p.Met322Ile,YP_009724397.2:p.Met322Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. Agerer 2021 https://doi.org/10.1126/sciimmunol.abg6461 doi:10.1126/sciimmunol.abg6461 33664060 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29247 T325I NC_045512.2:g.974C>T YP_009724397.2:p.Thr325Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes partial loss of T cell line responsiveness and CTL killing ability by B*40:01-restricted CD8+ N epitope MEVTPSGTWL 322-331. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29247 T325I NC_045512.2:g.974C>T YP_009724397.2:p.Thr325Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29266,29266 L331F,L331F NC_045512.2:g.993G>T,NC_045512.2:g.993G>C YP_009724397.2:p.Leu331Phe,YP_009724397.2:p.Leu331Phe nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. Agerer 2021 https://doi.org/10.1126/sciimmunol.abg6461 doi:10.1126/sciimmunol.abg6461 33664060 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29409 T379I NC_045512.2:g.1136C>T YP_009724397.2:p.Thr379Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 335 R24C NC_045512.2:g.70C>T YP_009724389.1:p.Arg24Cys YP_009724389.1:Arg24Cys open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (25x overrepresentation vs expected count of 514 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 347 V28I NC_045512.2:g.82G>A YP_009724389.1:p.Val28Ile YP_009724389.1:Val28Ile open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (30x overrepresentation vs expected count of 143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 383 S40P NC_045512.2:g.118T>C YP_009724389.1:p.Ser40Pro YP_009724389.1:Ser40Pro open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~58 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 396 Q44L NC_045512.2:g.131A>T YP_009724389.1:p.Gln44Leu YP_009724389.1:Gln44Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~19 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 443 V60I NC_045512.2:g.178G>A YP_009724389.1:p.Val60Ile YP_009724389.1:Val60Ile open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 489 D75G NC_045512.2:g.224A>G YP_009724389.1:p.Asp75Gly YP_009724389.1:Asp75Gly open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 490,490 D75E,D75E NC_045512.2:g.225T>G,NC_045512.2:g.225T>A YP_009724389.1:p.Asp75Glu,YP_009724389.1:p.Asp75Glu YP_009724389.1:Asp75Glu,YP_009724389.1:Asp75Glu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~20 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) immunosuppression variant emergence Emergent as 22% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing. Avanzato 2020 https://doi.org/10.1016/j.cell.2020.10.049 doi:10.1016/j.cell.2020.10.049 33248470 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) IFN activity Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-517) was tested in vitro for IFN response. Lin 2021 https://doi.org/10.1016/j.chom.2021.01.015 doi:10.1016/j.chom.2021.01.015 33548198 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) IFN activity Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-523) was tested in vitro for IFN response. Lin 2021 https://doi.org/10.1016/j.chom.2021.01.015 doi:10.1016/j.chom.2021.01.015 33548198 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) IFN activity Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 500-523) was tested in vitro for IFN response. Lin 2021 https://doi.org/10.1016/j.chom.2021.01.015 doi:10.1016/j.chom.2021.01.015 33548198 True Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,509,518 M85V,M85V,M85V NC_045512.2:g.253A>G,NC_045512.2:g.253A>G,NC_045512.2:g.253A>G YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val YP_009724389.1:Met85Val,YP_009724389.1:Met85Val,YP_009724389.1:Met85Val open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 508 H81Q NC_045512.2:g.243T>A YP_009724389.1:p.His81Gln YP_009724389.1:His81Gln open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (30x overrepresentation vs expected count of ~20 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 510 M85K NC_045512.2:g.254T>A YP_009724389.1:p.Met85Lys YP_009724389.1:Met85Lys open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~12 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 561 R99H NC_045512.2:g.296G>A YP_009724389.1:p.Arg99His YP_009724389.1:Arg99His open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 563 S100C NC_045512.2:g.298A>T YP_009724389.1:p.Ser100Cys YP_009724389.1:Ser100Cys open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (33x overrepresentation vs expected count of ~19 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 593 H110Y NC_045512.2:g.328C>T YP_009724389.1:p.His110Tyr YP_009724389.1:His110Tyr open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (22x overrepresentation vs expected count of ~514 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 593 H110D NC_045512.2:g.328C>G YP_009724389.1:p.His110Asp YP_009724389.1:His110Asp open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~11 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 606 I114T NC_045512.2:g.341T>C YP_009724389.1:p.Ile114Thr YP_009724389.1:Ile114Thr open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (155x overrepresentation vs expected count of ~58 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 657 A131V NC_045512.2:g.392C>T YP_009724389.1:p.Ala131Val YP_009724389.1:Ala131Val open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~514 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 677 A138T NC_045512.2:g.412G>A YP_009724389.1:p.Ala138Thr YP_009724389.1:Ala138Thr open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 761 S166G NC_045512.2:g.496A>G YP_009724389.1:p.Ser166Gly YP_009724389.1:Ser166Gly open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (132x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay -Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 798 N178S NC_045512.2:g.533A>G YP_009724389.1:p.Asn178Ser YP_009724389.1:Asn178Ser open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 36778462 False Paul Gordon Pokay +"organism" "reference accession" "reference database name" "nucleotide position" "original mutation description" "nucleotide mutation" "amino acid mutation" "amino acid mutation alias" "gene name" "gene symbol" "protein name" "protein symbol" "measured variant functional effect" "inferred variant functional effect" "viral life cycle functional effect" "variant functional effect description" "CVX code" "DrugBank Accession Number" "Antibody Registry ID" "author" "publication year" "URL" "DOI" "PMID" "peer review status" "curator" "mutation functional annotation resource" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "viral load" "" "" "This mutant causes a 0.41x fold change in the infectious virus production rate." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has a 0.66x fold change in EC50 value with Remdesivir." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has an inhibition rate of virus production by Remdesivir of 0.80." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has a 0.27x fold change in EC50 value with Remdesivir." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has an inhibition rate of virus production by Remdesivir of 0.78." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "viral load" "" "" "This mutant causes a 0.48x fold change in the infectious virus production rate." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.526 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.8x reduction in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,22992,23012,23664" "L5F,S477N,E484K,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 114 test-positive were Iota. Two dose vaccine efficacy against Iota was 95.7 (81.7-99.0%), one dose VE was 88.8 (0.7-98.7)%." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,25186" "L5F,Q1208H" "NC_045512.2:g.13C>T,NC_045512.2:g.3624G>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Gln1208His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Four of the convalescent sera tested showed 4-fold or greater improvement in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21587" "P9S" "NC_045512.2:g.25C>T" "YP_009724390.1:p.Pro9Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2M28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21597" "S12F" "NC_045512.2:g.35C>T" "YP_009724390.1:p.Ser12Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "A variant in low % circulation, predicted to have a similar effect to the experimentally verified S12P, which introduces a new signal peptide, altering cleavage to occur between residues C15 and V16, thereby eliminating the C15-C136 disulfide bond – similarly to escape mutants at positions C15 and C136. This in turn decreases to varying degrees N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600" "S13I" "NC_045512.2:g.38G>T" "YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The S13I mutation dampened binding of 5 mAbs and abrogated binding of 5 additional mAbs out of 11 neutralizing mAbs evaluated. Predicted to shift the signal peptide cleavage site from S13-Q14 to C15-V16, which can affect NTD conformation. PG: in saying S12F does not shift the signal peptide nor affect mAb binding, this manuscript appears to contradict the text of McCallum et al.'s earlier 2021 manuscript stating that S12F *does* affected some mAb binding via putative signal peptide shift." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018" "S13I,W152C" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The B.1.427/B.1.429 S13I/W152C NTD did not bind to any NTD-directed neutralizing mAbs, which are known to target a single antigenic site (antigenic site i), whereas binding of the non-neutralizing S2L20 mAb to the NTD antigenic site iv was not affected by any mutants, confirming proper retention of folding." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Antibody neutralization assays showed 6.7-fold resistance against 7/8 convalescent plasma." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Swab samples N/NP viral RNA is approximately 2-fold higher in B.1.427/B.1.429 than in non-variant viruses." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 9 plasma collected 15 to 28 days after early 2020 infections, neutralization reduced 4.9-fold for B.1.427/B.1.429 compared to wildtype (D614G). In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.427/B.1.429 pseudotyped virus, as well as WT and other VOCs." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using HIV pseudotype: Neutralization potency of 11 Moderna mRNA1273-elicited plasma (7-27 days post-2nd dose) was reduced ~2.8-fold compared to wildtype (D614G) S. It was reduced ~4-fold in 14 Pfizer/BioNtech BNT162b2-elicited plasma (7-27 days post-2nd dose). Using VSV pseudotype: we observed a 3-fold average reduction of Pfizer/BioNtech BNT162b2-elicited plasma neutralizing activity." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.249 (1.7-fold). Neutralization against 10 convalescent plasma was somewhat poorer (3.1-fold)." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "14 of 34 RBD-specific mAbs showed reduced neutralization to the B.1.427/B.1.429 variant pseudotype." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Lineages bearing these spike mutations comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the ""California"" or ""West Coast"" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI:1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020." "" "" "" "Peng" "2021" "https://doi.org/10.1093/cid/ciab283" "doi:10.1093/cid/ciab283" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.427/429 reduced 2.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "6 of 11 (55%) vaccine recipients (Moderna or Pfizer), showed 2x reduction in neutralization to a B.1.429 lineage virus." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 2.7x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 2.3x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403,25135" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G,K1191N" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3573G>T" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys1191Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for CAL.20C (B.1.429), and a slight decrease in CD8+ percentage (p=0.0201) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21604,21604" "Q14H,Q14H" "NC_045512.2:g.42G>C,NC_045512.2:g.42G>T" "YP_009724390.1:p.Gln14His,YP_009724390.1:p.Gln14His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21605" "C15R" "NC_045512.2:g.43T>C" "YP_009724390.1:p.Cys15Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21606" "C15F" "NC_045512.2:g.44G>T" "YP_009724390.1:p.Cys15Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates neutralization by N-terminal-domain-targeting mAbs 4-19. Impairs neutralization by N-terminal-domain-targeting mAbs 4A8 and 2-17." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggetsing that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132" "L18F,T20N,P26S,D138Y,R190S" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The neutralization titer of NTD-binding mAb159 was 133-fold reduced on P.1 compared to Victoria (~wild type), with only 64% neutralization at 10 μg/mL. Residues 20, 18, and 138 form a cluster underlying the 245–259 loop, which inserts into a groove between the light and heavy chains of Fab 159. In addition, the N-terminal residues preceding residue 18 interact with the antibody and may be perturbed. Given that there is likely a single supersite (""i"") for potent NTD-binding antibodies, the binding of many of these are likely affected. Using 20 potent (primaruly anti-RBD) antibodies, neutralization was measured by a focus reduction neutralization test (FRNT) and compared with neutralization of Victoria (~wild type) and variants B.1.1.7 and B.1.351. Compared to Victoria neutralization by the mAbs was significantly impacted by P.1, with 12/20 showing > 10-fold reduction in FRNT50 titer and a number showing complete knockout of activity. The results with P.1 showed a greater impact compared to B.1.1.7 but were, as expected, similar to those with B.1.351." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Amongst RBD-targeting Emergency Use Authorized monoclonal antibody treatments CB6, LY-CoV555 and REGN10933 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1, but REGN10987 activity remains strong. RBD-targeting monoclonal antibodies 2-15 and C121 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. N terminal domain targeting monoclonal antibodies 5-7, 4-8, 4-18 and 2-17 have abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 12 Moderna vaccinee sera 15 days post second dose (43 days since first vaccination), an average 2.8x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 4.8x decrease against the full P.1 type vs WA-1 was observed, though overall with a higher ID50 reciprocal value. In 10 Pfizer vaccinee sera 7 days or more post second dose (28 days or more since first vaccination), an average 2.2x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.8x decrease against the full P.1 type vs WA-1 was observed, with similar variant ID50 reciprocal value." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the “up” position." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In convalescent sera one month or more post-infection in Spring 2020, an average 6.5x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.4x decrease against the full P.1 type vs WA-1 was observed, with better full P.1 ID50 reciprocal value compared to the 10-mutation model." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "After a 128 day interval, a patient in Sao Paulo State, Brazil reinfected with P.1 (first episode likely predates P.1 emergence). Both cases were fairly mild (difficulty breathing, tiredness, dizziness and fatigue)." "" "" "" "Malta Romano" "2021" "https://doi.org/10.1590/S1678-9946202163036" "doi:10.1590/S1678-9946202163036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Gamma (P.1) variant is 0.6x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 3.0x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 4.1x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 349 test-positive were Gamma. Two dose vaccine efficacy against Gamma was 95.5 (90.9-97.8%), one dose VE was 74.2 (43.8-88.1%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Three healthcare workers (29-50yo) had confirmed P.1 [Gamma] re-infection in the Amazonas region of Brazil 3-9 months after initial infection from viruses with distinct lineage from P.1, but mild symptoms upon re-infection and evidence for infectiousness during re-infection." "" "" "" "Naveca" "2021" "https://doi.org/10.21203/rs.3.rs-318392/v1" "doi:10.21203/rs.3.rs-318392/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x cleavage of S2 relative to WA1 (D614G) wildtype by Gamma variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but H655Y is upstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly lower against B.1.1.248 variant constellation in sera tested from most of the 15 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped P.1 virus has reduced neutralization activity vs wild type: 6.7x (30 sera Pfizer median 9 days post 2nd dose) and 4.5x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Unlike wild type or B.1.1.7, P.1 lineage virus was able to infect and replicate in common lab mouse strains, with high titer." "" "" "" "Montagutelli" "2021" "https://doi.org/10.1101/2021.03.18.436013" "doi:10.1101/2021.03.18.436013" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.248 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07. B.1.1.248 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.7 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0039 for mild resistance." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.248 variant constellation in 10 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples, P=0.0020." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 16.6% in this B.1.1.248 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Among 46,884 HCWs in Manaus, Brazil vaccinated with at least one dose of CoronaVac, a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%; 95% CI, 11.3 - 71.4) in the odds of symptomatic SARS-CoV-2 infection was observed during the period 14 days or more after receiving the first dose. Estimated vaccine effectiveness of at least one dose against any SARS-CoV-2 infection was 35.1% (95% CI, −6.6 - 60.5) in the same time period." "" "" "" "Hitchlings" "2021" "https://doi.org/10.1101/2021.04.07.21255081" "doi:10.1101/2021.04.07.21255081" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.15x *increase* in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Neutralizing antibodies that were generated following a mild infection with SARS-CoV-2 B.1.128 were effective in vitro, and likely protective, against the SARS-CoV-2 P.1. variant in the majority of individuals based on 60 convalescent sera tested." "" "" "" "Mendes-Correa" "2021" "https://doi.org/10.1101/2021.05.11.21256908" "doi:10.1101/2021.05.11.21256908" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "VSV pseudotype P.1 showed 4.8-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections)." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype P.1 showed slight decrease in cell entry relative to wild type in 262T and 263T-ACE2 (kidney) cell lines. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "VSV pseudotype P.1 entry mediated by the S proteins of the P.1 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Cell fusion proficiency was slight impaired. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for P.1 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the P.1 variants used, using the most popular as a stand in]" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against P.1 at various time points using pseudovirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 85%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 256 for B.1.1.7 virus. Compare to somewhat stronger neutralization titer for wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "PBMCs of 11 mild COVID-19 patients collected 38-80 days after symptom onset were stimulated with the 15-mer peptide pools (w/ 10 residue overlaps) from the wholle viral proteome, showing no significant CD4+ cell count effect for P.1, and a slight increase in CD8+ percentage (p=0.0195) by Activation Induced Marker (AIM) assay (cellular immunity measurement). [in the text, this increase is not noted as signficant, even though p=0.05 is used elsewhere in the text as a signficance threshold]" "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "P.1 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with Lilly mAb combination LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of P.1. There was also escape from neutralization of P.1 by REGN10933 (one of 2 in Regeneron's mAb cocktail) and a modest reduction in neutralization of P.1 by AstraZeneca's AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized P.1 with all reaching a plateau at 100% neutralization; interestingly, ADG30 showed a slight increase of neutralization of P.1. S309 Vir was largely unaffected, although for several viruses, including P.1, the antibody failed to completely neutralize, conceivably reflecting incomplete glycosylation at N343, since the sugar interaction is key to binding of this antibody." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The relative transmissibility of P.1 estimated at the national level (Italy) varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. PG: variant list has been abbreviated due to mixed K417 bases in this lineage, potential miscalls of deletions" "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21801,22206,22334,22600,22600,22810,22811,22812,22813,22813,22879,22881,22882,22882,22986,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D80A,D215G,W258R,R346S,R346S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,A475V,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.772T>C,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1424C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ala475Val,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments and mutations from variants of concern completely ablates neutralization in 19 of 21 convalescents plasma collected mean 1.3 months post infection. [actual Y145del from manuscript substituted with more common Y144del description]" "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801" "L18F,D80A" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The L18F and D80A of the B.1.351 lineage lead to reconfiguration of the N-terminal segment despite the disulfide between Cys16 and Cys136 that partly anchors the N-terminal peptide. The most consequential changes are probably from the triple residue deletion... which causes a shift of the nearby loop 144-155 and must also reconfigure the adjacent disorder loop (residues 246-260), both of which form part of the neutralizing epitopes...bringing large changes in the antigenic surface in this region." "" "" "" "Cai" "2021" "https://doi.org/10.1101/2021.04.13.439709" "doi:10.1101/2021.04.13.439709" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The 501Y.V2 to first wave IC50 ratio ranged from 6 to 200-fold. Averaging across all 7 participant convalescent sera highlighted the dramatic decrease in sensitivity to neutralization of authentic 501Y.V2 variants. PG: I'm purposefully ignoring D614G and A701V as contributors" "" "" "" "Cele" "2021" "https://doi.org/10.1038/s41586-021-03471-w" "doi:10.1038/s41586-021-03471-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~7-fold reduction in B.1.351 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike)." "" "" "" "Riddell" "2021" "https://doi.org/10.1101/2021.04.17.440246" "doi:10.1101/2021.04.17.440246" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike)." "" "" "" "Riddell" "2021" "https://doi.org/10.1101/2021.04.17.440246" "doi:10.1101/2021.04.17.440246" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pzifer vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1), but were all infected before 14 days post second vaccination." "" "" "" "Kustin" "2021" "https://doi.org/10.1101/2021.04.06.21254882" "doi:10.1101/2021.04.06.21254882" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals (5/9) and recipients of a only a single dose of mRNA vaccine (10/11) – heterotypic neutralization dropped to negligible levels, particularly against B.1.351." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR22 molecule had a 1.57x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "B.1.351 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of B.1.351. There was also escape from neutralization of B.1.351 by REGN10933 and a modest reduction in neutralization of B.1.351 by AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized B.1.351." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.054x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 8 for B.1.351 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Sera from individuals who have been infected with Delta does not have strong neutralising activity against Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Beta neutralizing antibodies is 0.803x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.351. We observed an increase (relative to D614G) in binding of soluble ACE2 to B.1.351, and to a much gearter extent to B.1.1.7, which both carry the N501Y mutation (see Fig 3)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Pseudotype lentivirus for the full B.1.351 Spike variant list shows increase affinity for ACE2 as measured by IC50. This is in contrast to B.1.1.7 which showed no major change, indicating that the shared N501Y mutation is the driver of affinity change, attentuated in the B.1.1.7 mutatioon set, but maintained in the B.1.351 lineage." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 6.3x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Beta Variant B.1.351 RBD significantly better than w.t. SARS-CoV-2 RBD. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.07x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed for B.1.351 a CD4+ cell count decrease (29%, p=0.00063) as well as CD8+ (33%, p=0.0016) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Encouragingly, we find that the majority of T cell responses in recipients of two doses of the BNT162b2 vaccine are generated by epitopes that are invariant between the [wildtype] and two of the current variants of concern (B.1.1.7 and B.1.351). In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals and recipients of a only a single dose of mRNA vaccine – heterotypic neutralization dropped to negligible levels, particularly against B.1.351." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 8.2x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 16/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.351, with similar results for the live virus." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Beta neutralizing antibodies is 0.899x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v2 virus has reduced neutralization activity vs wild type: 41.2x (30 sera Pfizer median 9 days post 2nd dose) and 20.8x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v2 reduced 7.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.351 sample. Contrast this with 1.4-fold reduction for just the pseudovirus combination of ""key"" B.1.351 mutations K417N+E484K+N501Y. WA1 and B.1.351 FRNT50 titers correlated weakly at the individual level, with some individual’s serum potently neutralizing WA1 while having FRNT50 for B.1.351 below the assay limit of detection (1:20)." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.351 pseudotyped virus model ablates neutralization by RBD-directed mAbs CB6, 4-20, 2-4, 2-43, 910-30, 2-302-15, LY-Cov555, C121. B.1.351 pseudotyped virus model severely impairs neutralization by RBD-directed mAb 1-20. B.1.351 pseudotyped virus model impairs neutralization by RBD-directed mAb REGN10933. B.1.351 pseudotyped virus model ablates neutralization by N-terminal-domain-directed mAbs 5-24, 4-8, 4A8, 4-19. B.1.351 pseudotyped virus model severely impairs neutralization by N-terminal-domain-directed mAb 2-17. B.1.351 pseudotyped virus model impairs neutralization by N-terminal-domain-directed mAb 5-7. PG: Live virus data for the same mAbs is similar, but 1-20 becomes severally impaired, REGN10933 activity is ablated, and Brii-196 becomes impaired." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "3.2x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "[Contrary to how this paper has been cited, Voysey et al. do NOT show evidence of decreased effectiveness of ChAdOx1 (AstraZeneca) against the South African B.1.351 lineage. Insufficient numbers reaching the primary study endpoint were available in that arm of the vaccine study to report any statistics from the South African participants. Additionally, the study period of the paper ended in November 2020, while the earliest reported case of this lineage is October (covariants.org), only becoming dominant by mid-November.]" "" "" "" "Voysey" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms had mean ~6x reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: while B.1.1.7 and D614G showed neutralization by nasal swab from only one different previously infected vacinee neutralizing at weeks 3 and 6, B.1.351 showed zero neutralization at either time point in any sample (and relatively impaired serum neutralization)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "A 1.8-fold drop in FRNT50 for B.1.351 was observed in 44 sera collected between 1 and 301 post-infection." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 0.036x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 99.7x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 6.7x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with all key mutations from B.1.351 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting some synergy between the mutations to decrease cell entry fitness (i.e. cell entry is liklely not the driver of this lineage's dominance)." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,23060,23061,23062,23063,22810,22811,22812,22813,22813,23012,23399,23401,23402,23403" "L18F,D80A,D215G,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The most significant loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against authentic B.1.351 lineage virus (9.2-fold). Neutralization against 10 convalescent plasma was poorer (18.7x)." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks." "" "" "" "Meister" "2021" "https://doi.org/10.1093/infdis/jiab260" "doi:10.1093/infdis/jiab260" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Parana state of Brazil, patients aged 20-29 years experienced a tripling of their case fatality rate (CFR), from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling comparing February to January in 2021. Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil. [this is somewhat indirect evidence that assume greatly increasing proportion of P.1 cases in March (70%) compared to February, but the first official ID of P.1 in Parana state (Feb 16th) may be due to testing procedures rather than actual prevalence]" "" "" "" "Santos de Oliviera" "2021" "https://doi.org/10.1101/2021.03.24.21254046" "doi:10.1101/2021.03.24.21254046" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22915,22916,22917,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 (Pfizer) vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains." "" "" "" "Mallm" "2021" "https://doi.org/10.1101/2021.04.27.21254849" "doi:10.1101/2021.04.27.21254849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Delta (B.1.617.2) shows mean 2.1x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Delta (B.1.617.2) shows 3.64x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22916,22917,23012,23399,23401,23402,23403" "T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this lineage defining mutation combination from B.1.617.3 increased syncytium formation ~2.3x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22916,22917,23012,23399,23401,23402,23403" "T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this lineage defining mutation combination from B.1.617.3 conferred a ~11.8x drop in neutralization (NT50) [suggesting role for T19R and T95I in half the sera]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22916,22917,23012,23399,23401,23402,23403" "T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this lineage defining mutation combination from B.1.617.3 conferred a ~4.5x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,23399,23401,23402,23403" "T19R,T95I,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22028,22915,22916,22917,23604,23399,23401,23402,23403,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,E156del,L452R,L452R,L452R,P681R,D614G,D614G,D614G,D614G,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.467_472del,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4.5x cleavage of S2 relative to WA1 (D614G) wildtype by Delta (B.1.617.2) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~3.5x for closely related Kappa B.1.617.1 also with P681R at the cleavage site)." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. [Mutation list in publication appears to contain a typo with R158del instead of R158G]" "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 4.0x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Modelling the Delta variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increased 11x relative to wild type (15.3 vs 1.4). [del ~157 truncated due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a coinfection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 2.6x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.020x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.10x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In primary human airway epithelial cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 1.9x relative to wild type (2.7 vs 1.4). This is the Delta variant with the P681R furin cleavage site mutation absent. [del ~157 truncated due to ambiguity]" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Plasma neutralizing activity was also assessed against SARS-CoV-2 Delta, Omicron BA.1, BA.2 and BA.4/5 variants using viruses pseudotyped with appropriate variant spikeproteins. Delta breakthrough infection resulted in 15-fold increased neutralizing titers." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Plasma neutralizing activity in 49 participants was measured using HIV-1 pseudotyped with the 100 WT SARS-CoV-2 spike protein. Delta breakthrough infection resulted in 11-fold increased geometric mean half-maximal neutralizing titer (NT50)." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Delta neutralizing antibodies is 0.872x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Delta Variant B.1.617.2 RBD or w.t. SARS-CoV-2 RBD with nearly equal potency determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 507 pM for binding to the Delta B.1.617.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Delta neutralizing antibodies is 0.952x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "The incidence rate of Covid-19 during the Delta-dominant period (Jul-Aug 2021) was lower for late vaccinated (49.0/1000 person-years) [formerly placebo] versus early vaccinated (77.1/1000 person-years) participants in the Moderna mRNA-1273 Phase 3 trials, representing a 36.4% VE reduction (95% CI 17.1%-51.5%). There were fewer severe Covid-19 cases in the late group (6; 6.2/1000 person-years) than early (13; 3.3/1000 person-years), representing a 46.0% reduction (95% CI −52.4%-83.2%). Three Covid-19 related hospitalizations occurred with two resulting deaths in the early group." "" "" "" "Baden" "2021" "https://doi.org/10.1101/2021.09.17.21263624" "doi:10.1101/2021.09.17.21263624" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.92x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Delta Molnupiravir (MK-4482) had ~4x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001)." "" "" "" "Chia" "2021" "https://doi.org/10.1101/2021.07.28.21261295" "doi:10.1101/2021.07.28.21261295" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001)." "" "" "" "Chia" "2021" "https://doi.org/10.1101/2021.07.28.21261295" "doi:10.1101/2021.07.28.21261295" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance." "" "" "" "Twohig" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance." "" "" "" "Twohig" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccination of health care workers in Delhi was started in early 2021, with the ChdOx-1 (Astra Zeneca) vaccine. Surveillance has suggested B.1.1.7 dominance in the Delhi area during early 2021, with growth of B.1.617 since March 2021. During the wave of infections during March and April an outbreak of SARS-CoV-2 was confirmed in 33 vaccinated staff members at a single tertiary centre (age 27-77 years). Sequencing revealed that 16/33 were B.1.617.2, with a range of other B lineage viruses including B.1.1.7 for the rest except one A lineage case. Importantly no severe cases were documented in this event." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Case 62541 cluster in Singapore included a fully vaccinated nurse 2 months post-vaccine [likely Pfizer based on dates and supply], and a doctor of unknown vaccine status. This cluster was caused by a B.1.617.2 virus [via crossreference to" "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Denmark, for the period Jan 1 to Jun 27, 2021, Delta variant was associated with increased an risk ratio of 2.83 [95% CI 2.02–3.98] for hospitalization." "" "" "" "Bager" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.2 aka Delta) showed a 2.34x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.89x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Delta (B.1.617.2) has an IC50 fold change of 46.5x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Delta (B.1.617.2) variant is 0.6x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Delta (B.1.617.2) has an IC50 fold change of 0.57x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Delta (B.1.617.2) has an IC50 fold change of 0.87x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Delta (B.1.617.2) has an IC50 fold change of 0.15x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,23399,23401,23402,23403" "T19R,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21627" "T22I" "NC_045512.2:g.65C>T" "YP_009724390.1:p.Thr22Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain, frequently observed in various human infection lineages, reduces the tropism of SARS-CoV-2 in F81 (cat kidney, Felis catus) and BHK-21 (golden hamster kidney, Mesocricetus auratus) cell line cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21648" "T29I" "NC_045512.2:g.86C>T" "YP_009724390.1:p.Thr29Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21717,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23399,23401,23402,23403,23593,23593,24224" "Q52R,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,D614G,D614G,D614G,D614G,Q677H,Q677H,F888L" "NC_045512.2:g.155A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C" "YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.525 reduced 4.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21717,23012,23593,23593,24224" "Q52R,E484K,Q677H,Q677H,F888L" "NC_045512.2:g.155A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C" "YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The B.1.525 appears to have poor transmissibility when in competition with B.1.1.7 and other circulating strains in Denmark (early 2021)." "" "" "" "Albertsen" "2021" "https://www.covid19genomics.dk/2021-05-08_data-overview.html#b1525" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21752,21752" "W64R,W64R" "NC_045512.2:g.190T>A,NC_045512.2:g.190T>C" "YP_009724390.1:p.Trp64Arg,YP_009724390.1:p.Trp64Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21759" "H66R" "NC_045512.2:g.197A>G" "YP_009724390.1:p.His66Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent, especially on a D614 wildtype background." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Neutralization activity of almost all Moderna Phase 1 sera tested actually *increased*." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This deletion outside the receptor binding domain in pseudotyped VSV promoted the capacity of pseudotyped VSV to transduce black flying fox (Pteropus alecto) kidney PabKi.1 cells (17.8%) to a level twice that of human epithelial-like Huh-7 cells (9.8%)" "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduces neutralization by structurally unmapped mAb COVA1-21 (cluster XI)." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization activity of almost all convalescent sera tested decreased ~2x." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "The delH69/V70 enhances viral infectivity, indicating its effect on virus fitness is independent to the N501Y RBM change [with which it is found in lineage B.1.1.7] Possibly arisen as a result of the virus evolving from immune selection pressure in infected individuals and possibly only one chronic infection in the case of lineage B.1.1.7." "" "" "" "Kemp" "2020" "https://doi.org/10.1101/2020.12.14.422555" "doi:10.1101/2020.12.14.422555" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No notable change in neutralization efficiency, despite N439K by itself showing a ~2x decrease on average in 16 health workers' convalescent sera." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization activity of convalescent sera tested decreased ~2x with this B.1.1.7 pseudotyped virus." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron (a.k.a. B.1.1.529) Spike pseudotyped VSV and Vero E6 cells has somewhat reduced neutralization (2.7x) vs wild type with monoclonal antibody Sotrovimab (a.k.a. VIR-7831). [delins at 214 omitted for syntax compatibility]" "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron breakthrough infection after 3-dose vaccination resulted in a further 3.5-fold and 2.9-fold increase of Omicron BA.1 and BA.2 neutralizing titers. Omicron BA.4/5 showed the highest neutralization resistance of all variants tested, resulting in low geometric mean neutralizing titers in plasma samples obtained after the second vaccine dose (NT50=72)." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron B.1.1.529 (BA.1) neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron (B.1.1.529 [BA.1]) have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Omicron variant and was used to determine neutralizing antibodytitres. There was a 114.84x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 6.61x fold increase in antibody response pre-reinfection. There was a 1194.9x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Omicron BA.1 variant is 1.0x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.1 has an IC50 fold change of 0.30x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 73 pM for binding to the Omicron B.1.1.529. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigms’ ACE-2 variant LVE/STR chimera binds to SARS-2 Omicron variant B.1.1.529 spike protein trimer with high affinity. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Omicron BA.1 has an IC50 fold change of 1.26x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Delta variant and was used to determine neutralizing antibodytitres. There was a 24.63x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 4.21x fold increase in antibody response pre-reinfection. There was a 39.27x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.1 has an IC50 fold change of 0.08x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Omicron BA.1 has an IC50 fold change of 0.38x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "All 10 individuals with 3 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 3319 NT50." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "All 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 729 NT50." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against B.1 variant and was used to determine neutralizing antibodytitres. There was a 6.76x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 2.06x fold increase in antibody response pre-reinfection. There was a 8.18x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.3 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.3 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was somewhat lower against B.1.1.7 in sera tested from most of the 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.7 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2489." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.1.7 sample. Contrast this with 1.3-fold reduction for just the pseudovirus combination of ""key"" B.1.1.7 mutation N501Y." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild to modest decrease in infection rate amongst the cells, suggesting a net mild negative effect on human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing moderate decrease in infection rate amongst the cells, significantly lower than the deletion or Y453F alone, or their combination, suggesting a synergistic effect on poorer human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, much closer to D614G activity level than Y453F alone, suggesting compensatory effects between the deletion and the mutation in human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,23399,23401,23402,23403,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,D614G,D614G,D614G,D614G,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.298 virus has reduced neutralization activity vs wild type: 1.4x (30 sera Pfizer median 9 days post 2nd dose) and 1.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells, markedly higher infectivity than either mutation alone, suggesting a synergistic net neutral effect on human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from Mink Cluster 5 was neutralized more easily than D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with all key mutations from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (~50%) decrease in infection rate amongst the cells, suggesting that this anthropozoonotic event is driven by other factors at the expense of human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7+E484K reduced 2.8x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Compare with 1.2x reduction for B.1.1.7 without E484K." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization capacity GMT of 27 subjects' sera post-infection was markedly worse against B.1.1.7 + E484K than the lineage alone, with a 11.4x drop." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation combination causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x). PG: these effects are laregly missing in the deletion-alone data" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." "" "" "" "van Loon" "2021" "https://doi.org/10.1101/2021.04.15.21255389" "doi:10.1101/2021.04.15.21255389" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." "" "" "" "van Loon" "2021" "https://doi.org/10.1101/2021.04.15.21255389" "doi:10.1101/2021.04.15.21255389" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "A higher proportion of cases infected with the B.1.1.7 variant were hypoxic on admission compared to other variants (70.0% vs 62.5%, p=0.029), in London between March 13th 2020 and February 17th 2021 (400 B.1.1.7 cases out of 1470 total sequenced)." "" "" "" "Snell" "2021" "https://doi.org/10.1101/2021.03.16.21253377" "doi:10.1101/2021.03.16.21253377" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, moreso than this combination with the addition of P681H." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "clinical indicators" "" "" "After adjusting for the age factor, in a prospective Chinese cohort study B.1.1.7 variant infection (compared to B.1.140) was the risk factor for C-reactive protein (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), Serum amyloid A (0.011, 5.031, [1.459, 17.354]), Creatine Kinase (0.034, 4.34, [0.05, 0.91]), CD4+ T lymphocyte (0.029, 3.31, [1.13, 9.71]), and Ground Glass Opacity (0.005, 5.418, [1.656, 17.729])" "" "" "" "Song" "2021" "https://doi.org/10.1101/2021.05.04.21256655" "doi:10.1101/2021.05.04.21256655" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion)." "" "" "" "Marquez" "2021" "https://doi.org/10.1017/ice.2021.195" "doi:10.1017/ice.2021.195" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Second infection in December 2020 with B.1.1.7 after April 2020 initial infection with B.2 in a 78-year-old man with a history of Type 2 diabetes mellitus, diabetic nephropathy on hemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnea, ischemic heart disease, with no history of immunosuppression." "" "" "" "Harrington" "2021" "https://doi.org/10.1093/cid/ciab014" "doi:10.1093/cid/ciab014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM for binding to the Alpha B1.1.7. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Lessens the potency of mAbs COVA2-17 (~5x, similar to N501Y alone), COVA1-12 (~11x) and COVA1-21 (>100x), which do not compete allosterically." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 1.7x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.7 pseudotyped virus model impairs binding by RBD-directed mAb 910-30. B.1.1.7 pseudotyped virus model abolishes N-terminal-domain-directed mAbs 5-24, 4-8, and 4A8. B.1.1.7 pseudotyped virus model impairs binding by N-terminal-domain-directed mAbs 2-17, 4-19, 5-7." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020. Possible reinfections were identified in 249 (0.7% [95% CI 0.6-0.8]) of 36509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants." "" "" "" "Graham" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20x resistence to mAb CQ038 by B.1.1.7 pseudotyped virus" "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Alpha Variant B.1.1.7 RBD significantly better than GenScript IgG FL18-740 w.t. ACE-2 mAB. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.1.7. We observed a dramatic increase (relative to D614G) in binding of soluble ACE2 to B.1.1.7, and to a lesser extent to B.1.351, which both carry the N501Y mutation (see Fig 3)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion)." "" "" "" "Marquez" "2021" "https://doi.org/10.1017/ice.2021.195" "doi:10.1017/ice.2021.195" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%)." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "aerosolization" "" "" "Alpha variant cases in a large campus study showed fine-aerosol shedding amongst unmasked participants remained significantly greater for alpha variant infections (18-fold, 95% CI, 3.4 to 92-fold) after adjusting for the increased viral RNA in MTS and saliva, the number of coughs during sampling sessions, and symptom. After controlling for the effect of masks and numbers of coughs during sampling, alpha variant infection was associated with a 100-fold (95% CI, 16 to 650-fold) increase in coarse- and a 73-fold (95% CI, 15 to 350-fold) increase in fine-aerosol RNA shedding." "" "" "" "Adenaiye" "2021" "https://doi.org/10.1093/cid/ciab797" "doi:10.1093/cid/ciab797" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2.5x cleavage of S2 relative to WA1 (D614G) wildtype by Alpha variant variant as measured by mass spectrometry of Vero-TMPRSS culture." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "First documented cases of domestic cat and dog infections with the B.1.1.7 strain." "" "" "" "Hamer" "2021" "https://doi.org/10.1111/tbed.14122" "doi:10.1111/tbed.14122" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 2.6x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the 47D10. Alpha (B.1.1.7) has an IC50 fold change of 0.40x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks." "" "" "" "Meister" "2021" "https://doi.org/10.1093/infdis/jiab260" "doi:10.1093/infdis/jiab260" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively." "" "" "" "Schuit" "2021" "https://doi.org/10.1093/infdis/jiab171" "doi:10.1093/infdis/jiab171" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively." "" "" "" "Schuit" "2021" "https://doi.org/10.1093/infdis/jiab171" "doi:10.1093/infdis/jiab171" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.44x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM analysis of B.1.1.7 demonstrates an increased propensity for 'up', receptor accessible conformation of the Spike protein trimer." "" "" "" "Cai" "2021" "https://doi.org/10.1101/2021.04.13.439709" "doi:10.1101/2021.04.13.439709" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 2/20 (10%) samples showed >10x reduction (sera collected ~1mo post Jan 2020 first wave in China). Neutralizing antibody titers of 8/20 samples (40%) decreased below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaulated against VSV pseudotypes: neutralized D614G at week 2, whereas B.1.1.7 started to be neutralized at week 3, although less efficiently than D614G. B.1.1.7 and D614G strains were similarly neutralized at week 4 (1 week after booster dose)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We observed a sharp decline in cases when ∼50% of the elderly population was 2 weeks beyond their first vaccination dose and at a time point during which the B.1.1.7 variant gained transmission dominance. In support of this finding, it was suggested that, after the first vaccination dose, more than 70% of patients develop neutralization antibodies,15 and the vaccine efficiency can reach 85%." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Live virus was tested ex vivo in reconstituted brochial epithelium, and out competed wild type." "" "" "" "Touret" "2021" "https://doi.org/10.1101/2021.03.22.436427" "doi:10.1101/2021.03.22.436427" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.39x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization assays of B.1.1.7 virus showed a reduction of 2.5-fold (14 days post 2nd dose AstraZeneca, n=15), 2.1-fold (28 days post 2nd dose AstraZeneca, n=10), and 3.3-fold (7-17 days post 2nd dose Pfizer-BioNTech, n=25). [D1119H was included in the original paper, assumed typographical error and changed to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 1 (B.1.1.7) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "NTD-specific nAbs showed a substantial (3-450x) decrease in neutralization potency against the recently reported highly transmissible B.1.1.7 variant of concern, whereas RBD-specific nAbs were either unaffected or showed lower decreases in potency." "" "" "" "Graham" "2021" "https://doi.org/10.1016/j.immuni.2021.03.023" "doi:10.1016/j.immuni.2021.03.023" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Modelling the Alpha variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 3.9x relative to wild type (5.4 vs 1.4). This is less efficient than Delta (11x vs wildtype using a P681R mutation instead). [del ~144 changed due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a co-infection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 virus has reduced neutralization activity vs wild type: 2.1x (30 sera Pfizer median 9 days post 2nd dose) and 2.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Note that Y145del was actually noted in the paper as the effect of their DNA construct, but this is equivalent at the protein level to the more commonly annotated Y144del." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Alpha (B.1.1.7) variant is 1.0x fold the wildtype in 42 COVI." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Alpha Molnupiravir (MK-4482) had ~2.75x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "NVX-CoV2373 [Novavax] vaccine in phase 3 trial was 89.7% (95% CI, 80.2-94.6) effective in preventing COVID-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8-99.5) and 86.3% (71.3-93.5) against the prototype strain and B.1.1.7 variant, respectively." "" "" "" "Heath" "2021" "https://doi.org/10.1101/2021.05.13.21256639" "doi:10.1101/2021.05.13.21256639" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Alpha (B.1.1.7) has an IC50 fold change of 1.19x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.1.7 lineage effectiveness was observed as 29.5% (95% CI [22.9,35.5]) against infection, and 54.1% against severe/critical/fatal disease (95% CI [26.1-71.9]). Two weeks or more after 2nd dose, effectiveness climbed to 89.5% [85.9,92.3] against infection, and 100% against severe/critical/fatal disease (95% CI [81.7,100])." "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24506" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,S982A" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Lilly's LY-CoV16 showed marked reduction in neutralization of B.1.1.7." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Sera neutralized the B1.1.7 isolate with a lower potency (2-fold; 95% CL: 1.5 – 3-fold), and those with the lowest homotypic neutralizing potency had undetectable heterotypic potency (2/25)." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23709,23604,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,T716I,P681H,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific replication effects" "" "" "In this report, by using a lower infectious dose, we demonstrate that B.1.1.7 (cultured sample Hong Kong/HKPU-00015/2021) exhibits higher infectivity and/or replication efficiency in the nasal epithelium. (Hamster model of infection)" "" "" "" "Mok" "2021" "https://doi.org/10.1101/2021.04.19.440414" "doi:10.1101/2021.04.19.440414" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7." "" "" "" "Graham" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7." "" "" "" "Graham" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies." "" "" "" "Muik" "2021" "https://doi.org/10.1126/science.abg6105" "doi:10.1126/science.abg6105" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies." "" "" "" "Muik" "2021" "https://doi.org/10.1126/science.abg6105" "doi:10.1126/science.abg6105" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The mortality hazard ratio associated with infection with [B.1.1.7] compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community (54906 matched pairs of participants who tested positive for SARS-CoV-2 in pillar 2 between 1 October 2020 and 29 January 2021). In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases." "" "" "" "Challen" "2021" "https://doi.org/10.1136/bmj.n579" "doi:10.1136/bmj.n579" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "20/29 sera after the first dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 variant of 3.2 ± 5.7. After the second dose, the GMT was markedly increased compared with the first-dose titres, with a fold change of 1.9 ± 0.9 (mean ± s.d.). Neutralization GMT of 27 subjects post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization capacity GMT of 27 subjects' sera post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036)." "" "" "" "Song" "2021" "https://doi.org/10.1101/2021.05.04.21256655" "doi:10.1101/2021.05.04.21256655" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype B.1.1.7 showed no significant difference in cell entry relative to wild type in 6 cell lines. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020, Rt of B.1.1.7 was 1.35x (95% CI 1.02-1.69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant." "" "" "" "Graham" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, but to a smaller extent than N501Y and the deletion alone." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Slight neutralization improvement on average in 16 health workers' convalescent sera." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "These key B.1.1.7 mutations as a combination neutralized slightly less well than D614G and this was noticeable in the lack of sera with high neutralizing titer for the viruses across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,21762,21763,21764,21765,21766,21766,23399,23401,23402,23403,22915,22916,22917" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 17.2x-fold lower (95% CI: 0.6x-0.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,21762,21763,21764,21765,21766,21766,23399,23401,23402,23403,22915,22916,22917" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 13.0-fold lower (95% CI: 4.2x-4.6x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,22810,22811,22812,22813,22813,23009,23010,23012,23013" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,K417N,K417N,K417N,K417N,K417N,E484A,E484A,E484A,E484A" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario, using a retrospective matched case (age, gender and onset date) study of 6,312 Omicron cases vs 8,875 Delta, the adjusted risk of hospitalization or death was 54% lower (HR=0.46, 95%CI: 0.27, 0.77) among Omicron cases, after adjusting for vaccination statis and time since 2nd shot. The ratio for >60yo was 0.55 (95%CI: 0.28-1.06), and <60yo was 0.30 (95%CI: 0.16-0.57)." "" "" "" "Ulloa" "2021" "https://doi.org/10.1101/2021.12.24.21268382" "doi:10.1101/2021.12.24.21268382" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,23009,23010,23012,23013" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,E484A,E484A,E484A,E484A" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection, evidenced by a reinfection hazard ratio of 2.39 (CI95: 1.88-3.11) relative to primary infection in the initial part of South Africa's 4th covid-19 wave (November 2021). In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. [minimal variant signature for Omicron (B.1.1.529) used based on H69del PCR dropout observed in November 2021 coincident with the rise of Omicron]" "" "" "" "Pulliam" "2021" "https://doi.org/10.1101/2021.11.11.21266068" "doi:10.1101/2021.11.11.21266068" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800" "D80N" "NC_045512.2:g.238G>A" "YP_009724390.1:p.Asp80Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800" "D80Y" "NC_045512.2:g.238G>T" "YP_009724390.1:p.Asp80Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This AA substitution outside the receptor binding domain in pseudotyped VSV promoted a 7.2% transduction rate in golden hamster cells, which was higher than that of human epithelial-like Huh-7 cells (6.6%)." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800,22188,22206,22597,22599,23012,23521,23522,23524,23525,23604" "D80Y,I210del,D215G,R346K,R346K,E484K,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.238G>T,NC_045512.2:g.629_631del,NC_045512.2:g.644A>G,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp80Tyr,YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.VOI.V2 (first identified in Angola) reduced 8.0x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated that there is no free energy change (ddG) for this variant (i.e. same stability as wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "One individual of 30 in the study, with HLA supertype HLA*A24:02, had a linear epitope that overlaps this variant of concern." "" "" "" "Redd" "2021" "https://doi.org/10.1101/2021.02.11.21251585" "doi:10.1101/2021.02.11.21251585" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolishes neutralizing activity of N-terminal-domain-directed mAb 4-19." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.351 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 71%, Day 209 54%. Detectable antibodies against B.1.351 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 79%, Day 209 58%. Detectable antibodies against B.1.351 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 63%, Day 43 100%, Day 119 71%, Day 209 79%. Decreased neutralization on some assays was seen especially in those vaccinees tested that were 71+." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In an Ontario long term care facility, cumulatively, weaker BNT162b2 vaccine stimulation, age/comorbidities, produced a ∼130-fold reduction in apparent neutralization titers in mean 88yo LTCH residents against Beta (B.1.351), relative to staff vaccinees against D614G wild type. 37.9% of 116 two-dose-mRNA-vaccinated residents had undetectable neutralizing antibodies to B.1.351. mRNA-1273 vaccinee sera displayed ~2 better neutralization than BNT162b2. [common defining B.1.351 mutations noted, as the manuscript does not provide details]" "" "" "" "Abe" "2021" "https://doi.org/10.1101/2021.08.06.21261721" "doi:10.1101/2021.08.06.21261721" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, 7 of 15 neutralized this B.1.351 pseudotype that includes the L242del, and only one had titers above 100. Only one of the 15 sera achieved 80% neutralization. [compare to 5 and 1 for pseudotype without the deletion]" "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~10-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~3 fold without the deletion] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were significant, but ~500x weaker than in previously infected patients after first dose." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v3 reduced 8.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Beta (B.1.351) variant is 0.4x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A two-dose regimen of (AstraZeneca) ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, vaccine efficacy against severe Covid-19 is undetermined." "" "" "" "Madhi" "2021" "https://doi.org/10.1101/2021.02.10.21251247" "doi:10.1101/2021.02.10.21251247" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination." "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Unlike wild type or B.1.1.7, B.1.351 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. PG: The virus used in these expriments has a non-typical deletion+sub in the 242 region." "" "" "" "Montagutelli" "2021" "https://doi.org/10.1101/2021.03.18.436013" "doi:10.1101/2021.03.18.436013" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Beta (B.1.351) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Beta (B.1.351) has an IC50 fold change of 0.15x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x cleavage of S2 relative to WA1 (D614G) wildtype by Beta variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but A701V is downstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Beta Molnupiravir (MK-4482) had ~1.75x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v1 virus has reduced neutralization activity vs wild type: 34.5x (30 sera Pfizer median 9 days post 2nd dose) and 27.7x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Beta (B.1.351) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination." "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Compared to Alpha (B.1.1.7) variant, odds of progressing to severe disease were 1.24-fold (95% CI: 1.11-1.39) higher for Beta. Odds of progressing to critical disease were 1.49-fold (95% CI: 1.13-1.97) higher. Odds of COVID-19 death were 1.57-fold (95% CI: 1.03-2.43) higher." "" "" "" "Abu-Raddad" "2021" "https://doi.org/10.1101/2021.08.02.21261465" "doi:10.1101/2021.08.02.21261465" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 34 convalescent cases 4–9 weeks following infection in June 2020, before the emergence of B.1.1.7, neutralization titers against B.1.351 were, on average, 13.3-fold reduced compared with an early Victoria sample (p < 0.0001). Significantly, 18 of 34 samples failed to reach 50% neutralization at a plasma dilution of 1:20, with a number showing a near total reduction of neutralization activity. In 13 convalescent cases 4–9 weeks following infection with B.1.1.7, neutralization titers against B.1.351 were, on average, 3.1-fold reduced compared with an early Victoria sample (p < 0.0001)." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Testing against B.1.351 the 20 most effective mAbs (19 anti-RBD, 1 anti-NTD) from a screen of 377 against wild type, 4 of 20 antibodies had >10-fold fall in neutralization titers, with most of these showing a complete knockout of activity. This is in line with the key roles of K417, E484, and N501, in particular E484, in antibody recognition of the ACE2 interaction surface of the RBD. Regeneron mAb cocktail: The neutralization of REGN10987 was unaffected by B.1.351, while REGN10933 was severely impaired (773-fold). AstraZeneca mAb cocktail: Neutralization by the AZ pair of antibodies was little affected on B.1.351 compared with Victoria." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.351 defining mutations: Significant shift to infection in those without pre-existing conditions (79.6% vs 89% for non-VOC cases). Significant increase in hospitalization rate (19.3% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.3% vs 0.6% for non-VOC cases). PG: seems to be different notations around the LAL deletion, using the minimal shared definition to catch as many as possible." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The B.1.351 variant constellation causes an ∼20-fold increase in affinity for ACE2 compared with Wuhan RBD, which may influence transmissibility." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine plasma neutralization of B.1.351-spike virus was nominally robust but lower (~3x) than other variants of concern." "" "" "" "Liu" "2021" "https://doi.org/10.1056/NEJMc2102017" "doi:10.1056/NEJMc2102017" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "humoral response durability" "" "" "In a prospective study of 107 hospitalized patients, decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7 and P.1 variants for at least 6 months (last of two samples taken) in patients previously hospitalized for COVID-19. A weaker protection was however observed for the B.1.351 variant." "" "" "" "Betton" "2020" "https://doi.org/10.1093/cid/ciab308" "doi:10.1093/cid/ciab308" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Beta (B.1.351) has an IC50 fold change of 0.88x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using B.1.351 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~3-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~10 fold with L242del] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were signficiant, but >100x weaker than in previously infected patients after first dose." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, one third (5/15) of sera neutralized this B.1.351 pseudotype and only three had ID50 titers above 100. Only two of the 15 sera achieved 80% neutralization." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission." "" "" "" "Yinda" "2021" "https://doi.org/10.1101/2021.05.05.442780" "doi:10.1101/2021.05.05.442780" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Inoculation with the B.1.351 isolate resulted in lower clinical scores in 6 rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. Our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity." "" "" "" "Munster" "2021" "https://doi.org/10.1101/2021.05.07.443115" "doi:10.1101/2021.05.07.443115" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "4 health care workers in the 20's and 30's with no underlying conditions and seropositivity or confirmed 2020 SARS-CoV-2 infections were confirmed to have B.1.351 infection during a Februrary 2021 hospital outbreak in Luxembourg. Symptoms were mostly mild on first infection, and milder on second infection." "" "" "" "Staub" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.18.2100423" "doi:10.2807/1560-7917.ES.2021.26.18.2100423" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission." "" "" "" "Yinda" "2021" "https://doi.org/10.1101/2021.05.05.442780" "doi:10.1101/2021.05.05.442780" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer" "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.351 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the B.1.351 variants used, using the most popular as a stad in]" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In a Syrian hamster model, B.1.351 variant virus had >4x reduction in YRNT90 (measure of neutralization) using wild type convalescent sera. PG: Note that exact sequence for B.1.351 used was not disclosed." "" "" "" "Cochin" "2021" "https://doi.org/10.1101/2021.04.19.440435" "doi:10.1101/2021.04.19.440435" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "During an outbreak of SARS-CoV-2 501Y.V2 in a nursing home, all non-vaccinated residents (5/5) versus half of those fully vaccinated 2-5 weeks prior with BNT162b2 (13/26) were infected. Two of 13 vaccinated versus 4 of 5 non-vaccinated residents presented severe disease. BNT162b2 did not prevent the outbreak, but reduced transmission and disease severity. Among the 13 fully vaccinated residents who were infected, 2 (15.4%) presented with an asymptomatic disease, 9 (69.2%) developed mild to moderate symptoms, and 2 (15.4%) progressed to severe disease with fatal evolution secondary to acute respiratory distress syndrome (ARDS). There was no relationship between anti-S antibody levels at diagnosis and disease severity. Overall, the proportion of residents with severe disease in the non-vaccinated group (4/5) was higher than that in the vaccinated group (2/13). Only 1 vaccinated staff, but 10 unvaccinated were infected in the outbreak (no severe disease)." "" "" "" "Bailly" "2021" "https://doi.org/10.1093/cid/ciab446" "doi:10.1093/cid/ciab446" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer" "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v3 virus has reduced neutralization activity vs wild type: 42.4x (30 sera Pfizer median 9 days post 2nd dose) and 19.2x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.351 in 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.351 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0020 for moderate resistance." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.351 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. B.1.1.351 variant constellation ablates Class 3 N-terminal domain targeting antibodies COV2-2489 and COV2-2676 (the only two tested)." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine elicited antibodies neutralized virus with the B.1.351 spike protein had an average 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "VSV pseudotype B.1.351 entry mediated by the S proteins of the B.1.351 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.351 lineage effectiveness was observed as 16.9% (95% CI [10.4,23.0]) against infection, and 0% against severe/critical/fatal disease (95% CI [0-19.0]). Two weeks or more after 2nd dose, effectiveness climbed to 75.0% [70.5,78.9] against infection, and 100% against severe/critical/fatal disease (95% CI [73.7,100])." "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.351 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "VSV pseudotype B.1.351 showed 7.86-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections)." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype B.1.351 showed slight decrease in cell entry relative to wild type in 263T-ACE2 (kidney) cell line, and slight increase in Calu-3 (lung). Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abrogates Bamlanivimab, Etesevimab, or their combined use neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Approximately 6-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In one of eight cell lines tested (293T lung cells), a modest increase in cell entry was observed." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846" "T95I" "NC_045512.2:g.284C>T" "YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "65yo female with no severe Covid-19 risk factors tested positive 36 days after second dose of BNT162b2 (Pfizer) vaccine. Presented with fatigue, sinus congestion, and a headache developed; her symptoms plateaued and began to resolve six days later. [Mising genome coverage in regions of Spike covering clinically relevant mutations K417T, L452R, E484K, A701V, D796H, N501Y]" "" "" "" "Hacisuleyman" "2021" "https://doi.org/10.1056/NEJMoa2105000" "doi:10.1056/NEJMoa2105000" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22317,22319,22320,23399,23401,23402,23403" "T95I,D253G,D253G,D253G,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "B.1.526 (Iota) substantially increased IFR in older adults: by 46% (95% CI: 7.4 – 84%) among 45-64 year-olds, 82% (95% CI: 20 – 140%) among 65-74 year-olds, and 62% (95% CI: 45 – 80%) among 75+ during Nov 2020 – Apr 2021, compared to baseline IFR estimated for preexisting variants. [minimum clade defining mutations listed]" "" "" "" "Yang" "2021" "https://doi.org/10.1101/2021.08.04.21261596" "doi:10.1101/2021.08.04.21261596" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against B.1.621." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from vaccinees [ChAdOx1 and BNT162b2 primarily used in UK] shows decreased ability to neutralize B.1.621 compared to first wave virus and Alpha, with a magnitude of change similar to Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 69 test-positive were Mu. Two dose vaccine efficacy against Mu was 90.4% (73.9-96.5%), one dose VE was 45.8% (0.0-88.9%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Sera from individuals who have been infected with Delta does not have strong neutralising activity against B.1.621" "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 12.4x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. [This is a greater reduction than Beta @ 8.2x]" "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using live B.1.621 virus and a cytopathic effect-based assay, sera from 37 Pfizer/BioNTech BNT162b2 vaccinees collected 10-20 days post-booster showed significantly lower (95) but still ""robust"" neutralization than against ancestral B.1 virus (107)." "" "" "" "Messali" "2021" "https://doi.org/10.1002/jmv.27247" "doi:10.1002/jmv.27247" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 7.6x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. [This is a greater reduction than Beta @ 6.3x]" "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403" "T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 4.4-fold lower (95% CI: 4.3x-4.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403" "T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 1.5x-fold lower (95% CI: 0.05x-0.07x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,23012,23271,23399,23401,23402,23403,23604,23948" "T95I,E484K,A570D,D614G,D614G,D614G,D614G,P681H,D796H" "NC_045512.2:g.284C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2386G>C" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp796His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "51yo female with no severe COVID-19 risk factors tested positive 19 days after second dose of mRNA-1273 (Moderna) vaccine. Presented with sore throat, congestion, and headache developed; the next day she lost her sense of smell. Symptoms resolved over a one week period. Serum obtained 4 days after symptom onset was tested for neutralization against wild-type virus, the E484K mutant, and the B.1.526 variant. It was equally effective against each. These data suggest that the antibody response recognized these variants but was nonetheless insufficient to prevent a breakthrough infection. The virus detected matched neither B.1.1.7 nor B.1.526 VOC strains in wide circulation in New York at the time of infection, though shared some mutations." "" "" "" "Hacisuleyman" "2021" "https://doi.org/10.1056/NEJMoa2105000" "doi:10.1056/NEJMoa2105000" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,23399,23401,23402,23403" "T95I,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21855" "S98F" "NC_045512.2:g.293C>T" "YP_009724390.1:p.Ser98Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly enhanced the transduction rate in raccoon dog (Nyctereutes procyonoides) kidney (62.4%) and Rickett’s big-footed bat (Myotis pilosus) kidney (45.0%) cell cultures compared to epithelial-like human Huh-7 cells (38.9%)." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21929" "A123S" "NC_045512.2:g.367G>T" "YP_009724390.1:p.Ala123Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected in passage with mAb COV2-2489 during alanine mutagenesis antibody mapping experiment." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21969" "C136Y" "NC_045512.2:g.407G>A" "YP_009724390.1:p.Cys136Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massively decreases N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21969" "C136Y" "NC_045512.2:g.407G>A" "YP_009724390.1:p.Cys136Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected twice in passage with mAb COV2-2489." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. [PG: This mutation is adjacent to a well known deletion, which may confound the significance of this variant]" "" "" "" "Lucaci" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "These variants dominate in mink infections in North America, sometime supplemented with F486L. The Y453F variant found in other jurisdictions in mink infections is notably absent in North America." "" "" "" "" "2021" "https://doi.org/10.1101/2021.03.18.21253734v3" "doi:10.1101/2021.03.18.21253734v3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Kappa (B.1.617.1) shows 5.71x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Average 2x neutralization efficiency decrease against sera from 26 Phase II trial Covaxin (BBV152) vaccine recipents. Very similar to B.1.1.7 (~2x) in the same study, and the neutralization from 17 sera of natural infections across B1 lineages." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.04.23.441101" "doi:10.1101/2021.04.23.441101" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.1) showed a 1.12x increase in binding (KD) relative to D614G, but described as ""not significant"". [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cluster of B.1.617[.1] infections related to travel from India to USA, one patient with mild symptoms had received their second dose of Pfizer vaccine more than two weeks before the infection [i.e. vaccine breakthrough]." "" "" "" "Verghese" "2021" "https://doi.org/10.1128/JCM.00741-21" "doi:10.1128/JCM.00741-21" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617.1) showed a 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617.1) showed a 1.79x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~3.5x cleavage of S2 relative to WA1 (D614G) wildtype by Kappa (B.1.617.1) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~4.5x for closely related Delta B.1.617.2 also with P681R at the cleavage site)." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Kappa (B.1.617.1) shows mean 1.97x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Kappa (B.1.617.1) has an IC50 fold change of 2.3x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Kappa (B.1.617.1) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Kappa (B.1.617.1) has an IC50 fold change of 80.2x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Kappa (B.1.617.1) has an IC50 fold change of 0.68x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.2 has an IC50 fold change of 0.04x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Omicron BA.2 has an IC50 fold change of 0.09x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.2 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Omicron BA.2 has an IC50 fold change of 0.08x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.2 has an IC50 fold change of 0.07x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Omicron BA.2 variant is 0.8x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.2 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21974" "D138Y" "NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.43 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21977" "P139S" "NC_045512.2:g.415C>T" "YP_009724390.1:p.Pro139Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected once in passage with mAb COV2-2676." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990" "Y145del,Y145del" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990" "Y145del,Y145del" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient." "" "" "" "McCarthy" "2021" "https://doi.org/10.1126/science.abf6950" "doi:10.1126/science.abf6950" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990,21993,21995,23012,23399,23401,23402,23403" "Y145del,Y145del,H146del,H146del,E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.436_438del,NC_045512.2:g.436_438del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.His146del,YP_009724390.1:p.His146del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Normalized for particle number, on ACE2.293T cells showed that the B.1.618 spike protein was about as infective as D614G wild type." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21993,21995" "H146del,H146del" "NC_045512.2:g.436_438del,NC_045512.2:g.436_438del" "YP_009724390.1:p.His146del,YP_009724390.1:p.His146del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient." "" "" "" "McCarthy" "2021" "https://doi.org/10.1126/science.abf6950" "doi:10.1126/science.abf6950" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21997,21998,21999,22000,22001" "K147E,K147E,K147E,K147E,K147E" "NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G" "YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21997,21998,21999,22000,22001" "K147E,K147E,K147E,K147E,K147E" "NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G" "YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21998" "H146Y" "NC_045512.2:g.436C>T" "YP_009724390.1:p.His146Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in 4A8 monoclonal antibody EC50 (i.e. ablated recognition), but much milder effect on mAbs within antigenic supersite ""i""" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22001" "K147Q" "NC_045512.2:g.439A>C" "YP_009724390.1:p.Lys147Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22002" "K147T" "NC_045512.2:g.440A>C" "YP_009724390.1:p.Lys147Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22002" "K147T" "NC_045512.2:g.440A>C" "YP_009724390.1:p.Lys147Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massively decreases N terminal domain antigen recognition by supersite i mAbs S2M28, S2X28, S2X333, 4A8 (but not S2L28)." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22003" "K147N" "NC_045512.2:g.441A>T" "YP_009724390.1:p.Lys147Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22005" "N148S" "NC_045512.2:g.443A>G" "YP_009724390.1:p.Asn148Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong positive selection (up to 72% of supernatant sequences) under six rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22010" "K150E" "NC_045512.2:g.448A>G" "YP_009724390.1:p.Lys150Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong positive selection (up to 40% of supernatant sequences) under three rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22010" "K150E" "NC_045512.2:g.448A>G" "YP_009724390.1:p.Lys150Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22011" "K150T" "NC_045512.2:g.449A>C" "YP_009724390.1:p.Lys150Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 22% of supernatant sequences) after COV47 convalescent plasma assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22011" "K150R" "NC_045512.2:g.449A>G" "YP_009724390.1:p.Lys150Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 18% of supernatant sequences) under two rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22016,22016" "W152R,W152R" "NC_045512.2:g.454T>A,NC_045512.2:g.454T>C" "YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For NTD-binding neutralizing antibody ADI-56479 this mutation causes a 1000x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22016,22016" "W152R,W152R" "NC_045512.2:g.454T>A,NC_045512.2:g.454T>C" "YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22018" "W152C" "NC_045512.2:g.456G>T" "YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Pseudoviruses carrying the W152C mutation demonstrated small increases in cell entry compared to D614G alone in 293T cells and human airway organoids." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22018" "W152C" "NC_045512.2:g.456G>T" "YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The W152C mutation reduced recognition of six NTD neutralizing mAbs, including a complete loss of binding for two of them, with a complementary pattern to that observed for S13I (also found in lineage B.1.427/B.1.429) out of 11 neutralizing mAbs evaluated." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022" "E154K" "NC_045512.2:g.460G>A" "YP_009724390.1:p.Glu154Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Approximately 2-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abrogates Bamlanivimab neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Significant decrease in combined Etesevimab+Bamlanivimab neutralization except at the highest concentration measured. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In two of eight cell lines tested (Caco-2 intenstinal and Calu-3 lung), a modest increase in cell entry was observed. This increase was not observed in a Calu-3 cell line with overexpressed ACE2. [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pfizer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~3x (compared to ~11x for B.1.351). [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22028,22034" "R158G,R158G" "NC_045512.2:g.467_472del,NC_045512.2:g.472A>G" "YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22033,23012,23604" "F157L,E484K,P681R" "NC_045512.2:g.471C>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.23.1-v2 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22033,23604" "F157L,P681R" "NC_045512.2:g.471C>A,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.23.1-v1 reduced 1.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22036" "R158S" "NC_045512.2:g.474A>T" "YP_009724390.1:p.Arg158Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected three times in passage with mAb COV2-2489." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:03." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type C*07:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DPB1*04:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*16:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*07:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22107,22111" "Q183H,Q183H" "NC_045512.2:g.549G>T,NC_045512.2:g.549G>T" "YP_009724390.1:p.Gln183His,YP_009724390.1:p.Gln183His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome" "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132" "R190S" "NC_045512.2:g.570G>T" "YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.69 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604" "R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in B.1.640.2 variant was ~1000x folds more significant in 8 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604" "R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1.640.2 variant was ~5.6x folds more significant in 9 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22188,23399,23401,23402,23403" "I210del,D614G,D614G,D614G,D614G" "NC_045512.2:g.629_631del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "A 42yo Iranian male was reinfected with B.1.36 lineage virus 128 days after infection with genetically distinct B.1.36 virus, with negative PCR tests in between. In the first instance patient presented with cough, headache, severe diarrhea. In the second instance symptoms were more severe: body pain, shortness of breath, headache and anosmia. Anti-SARS-CoV-2 IgG and IgM tests were negative after both episodes. [Non-seroconversion may be associated with elevated risk of re-infection] [I210del is a homoplasy that has appeared in several disparate parts of the global phylogenetic tree, including A and B lineages, primarily in LMICs]" "" "" "" "Salehi-Vaziri" "2021" "https://doi.org/10.1016/j.virusres.2021.198421" "doi:10.1016/j.virusres.2021.198421" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:01." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*13:02." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:02." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.98 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227" "A222V,A222V" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227,23399,23401,23402,23403" "A222V,A222V,D614G,D614G,D614G,D614G" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "humoral response durability" "" "" "27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3), i.e. with a 9 month interval. Both cases were mild. No significant differences in the neutralizing capacity of the two lineages were observed in 4 sera taken (1 pre-reinfection, three post-reinfection). Neutralizing antibody titres (IC50) before and immediately after re-infection were <300 against both strains, and jumped >7x upon re-infection. Viral titres were also higher in the second case. Second case also includes N:p.A220V" "" "" "" "Brehm" "2021" "https://doi.org/10.3390/v13040661" "doi:10.3390/v13040661" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227,23399,23401,23402,23403" "A222V,A222V,D614G,D614G,D614G,D614G" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3). Both cases were mild. Second case also includes N:p.A220V" "" "" "" "Brehm" "2021" "https://doi.org/10.3390/v13040661" "doi:10.3390/v13040661" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22293" "L244S" "NC_045512.2:g.731T>C" "YP_009724390.1:p.Leu244Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22301" "S247R" "NC_045512.2:g.739A>C" "YP_009724390.1:p.Ser247Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22304" "Y248H" "NC_045512.2:g.742T>C" "YP_009724390.1:p.Tyr248His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22314" "P251L" "NC_045512.2:g.752C>T" "YP_009724390.1:p.Pro251Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317" "G252D" "NC_045512.2:g.755G>A" "YP_009724390.1:p.Gly252Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317,22319,22320" "D253G,D253G,D253G" "NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317,22319,22320" "D253G,D253G,D253G" "NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22319" "D253Y" "NC_045512.2:g.757G>T" "YP_009724390.1:p.Asp253Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22323" "S254Y" "NC_045512.2:g.761C>A" "YP_009724390.1:p.Ser254Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22323" "S254F" "NC_045512.2:g.761C>T" "YP_009724390.1:p.Ser254Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22326" "S255F" "NC_045512.2:g.764C>T" "YP_009724390.1:p.Ser255Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22328,22329,22331" "G257S,G257S,G257S" "NC_045512.2:g.769G>A,NC_045512.2:g.769G>A,NC_045512.2:g.769G>A" "YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334" "W258R" "NC_045512.2:g.772T>C" "YP_009724390.1:p.Trp258Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334" "W258R" "NC_045512.2:g.772T>C" "YP_009724390.1:p.Trp258Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334,22879,22881,22882,22882,22904,22910,23012" "W258R,N440K,N440K,N440K,N440K,N450D,N450D,E484K" "NC_045512.2:g.772T>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22340" "A260T" "NC_045512.2:g.778G>A" "YP_009724390.1:p.Ala260Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22344" "G261D" "NC_045512.2:g.782G>A" "YP_009724390.1:p.Gly261Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Multiple mink but no humans on one farm in Denmark, potential adaptation." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22377" "P272L" "NC_045512.2:g.815C>T" "YP_009724390.1:p.Pro272Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*02:01." "" "" "" "Dolton" "2021" "https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf" "doi:10.1101/2021.06.21.21259010v2.full.pdf" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22377" "P272L" "NC_045512.2:g.815C>T" "YP_009724390.1:p.Pro272Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*08:01." "" "" "" "Dolton" "2021" "https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf" "doi:10.1101/2021.06.21.21259010v2.full.pdf" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 1.2x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.3 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22583" "V341I" "NC_045512.2:g.1021G>A" "YP_009724390.1:p.Val341Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22599" "R346T,R346T,R346T,R346T" "NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22599" "R346T,R346T,R346T,R346T" "NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22599,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22939,22942,22942,22992,23009,23010,23012,23013,23027,23029,23030,23031,23053,23054,23055,22992,22995,23060,23061,23062,23063,23071,23074,23075" "R346T,R346T,R346T,R346T,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N460K,N460K,N460K,S477N,E484A,E484A,E484A,E484A,F490S,F490S,F490S,F490S,Q498R,Q498R,Q498R,T478K,T478K,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H" "NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The hACE2-binding affinity of XBB.1.5 RBD has a dissociation constant KD of 3.4 nM, where S486P is the distinguishing Spike mutation vs parent XBB.1 RBD with a much weaker KD (19 nM), as measured by surface plasmon resonance (SPR) assays." "" "" "" "Yue" "2023" "https://doi.org/10.1101/2023.01.03.522427" "doi:10.1101/2023.01.03.522427" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346K,R346K" "NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346I,R346I" "NC_045512.2:g.1037G>T,NC_045512.2:g.1037G>T" "YP_009724390.1:p.Arg346Ile,YP_009724390.1:p.Arg346Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Provides ~80% escape from mAb COV2-2130, even though its appearance in culture is formed without selective mAb pressure." "" "" "" "Dong" "2021" "https://doi.org/10.1101/2021.01.27.428529" "doi:10.1101/2021.01.27.428529" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346K,R346K" "NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation, which has emerged in some Omicron sequences, has a 0.7x reduction in neutralization activity with Sotrovimab in a VSV model on Vero E6 cells. [Omicron sequences with R346K may very well have a non-additive neutralization rather than 2.7x+0.7x = 3.4x]" "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346K,R346K" "NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 53% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 2/3 antibody C603." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 2/3 antibody C603." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 30% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22622" "N354D" "NC_045512.2:g.1060A>G" "YP_009724390.1:p.Asn354Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.13 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22624" "N354K" "NC_045512.2:g.1062C>A" "YP_009724390.1:p.Asn354Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22627,22629" "K356T,K356T" "NC_045512.2:g.1067A>C,NC_045512.2:g.1067A>C" "YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.14 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22629" "K356R" "NC_045512.2:g.1067A>G" "YP_009724390.1:p.Lys356Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22632" "R357K" "NC_045512.2:g.1070G>A" "YP_009724390.1:p.Arg357Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.18 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as ""stabilizing"" since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.72 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as ""stabilizing"" since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22661" "V367I" "NC_045512.2:g.1099G>A" "YP_009724390.1:p.Val367Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22679" "S373P" "NC_045512.2:g.1117T>C" "YP_009724390.1:p.Ser373Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Reduce affinity for mildly cross-reactive CR3022 (2003 pandemic SARS monoclonal antibody cross-reactive to SARS-CoV-2)" "" "" "" "Long" "2020" "https://doi.org/10.1128/mBio.02707-20" "doi:10.1128/mBio.02707-20" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22679,23009,23010,23012,23013" "S373P,E484A,E484A,E484A,E484A" "NC_045512.2:g.1117T>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "On December 7, 2021 the estimate of Omicron effective reproduction rate (Rt) is 3.12 [presumably R0 is higher], compared to 1.12 for the dominant Delta VOC at that time. [shorthand of variant list shraed by all contemporary BA lineage used here]" "" "" "" "" "2021" "https://doi.org/10.47326/ocsat.dashboard.2021.1.0" "doi:10.47326/ocsat.dashboard.2021.1.0" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22686" "S375F" "NC_045512.2:g.1124C>T" "YP_009724390.1:p.Ser375Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch." "" "" "" "Lucaci" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22696" "K378N" "NC_045512.2:g.1134G>T" "YP_009724390.1:p.Lys378Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for mildly neutralizing COV2-2677 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23402,23403" "P384L,D614G,D614G,D614G,D614G" "NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23402,23403" "P384L,D614G,D614G,D614G,D614G" "NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23402,23403" "P384L,D614G,D614G,D614G,D614G" "NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22745" "V395I" "NC_045512.2:g.1183G>A" "YP_009724390.1:p.Val395Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22766" "I402V" "NC_045512.2:g.1204A>G" "YP_009724390.1:p.Ile402Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22783,22784,22785,22786,22786" "R408S,R408S,R408S,R408S,R408S" "NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C" "YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22783,22784,22785,22786,22786,23009,23010,23012,23013,23060,23061,23062,23063" "R408S,R408S,R408S,R408S,R408S,E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a study of 481 vaccinees going from lowest to highest infection rate, 2 doses of CoronaVac and 1 dose of BNT162b2 had the lowest infection rate at 6.3%, then it was 3 doses of BNT162b2 having a infection rate of 16.6%. 2 and 3 doses of CoronaVac had 48.6% and 20.6% infection rate respectively. 2 doses of BNT162b2 has the highest infection rate at 49.2%." "" "" "" "Zhou" "2022" "https://doi.org/10.1101/2022.05.09.491254" "doi:10.1101/2022.05.09.491254" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates binding by RBD-directed mAbs CB6 and 910-30 (targeting the inner side of the RBD). Pseudotyped virus model impairs binding by RBD-directed mAbs 4-20 and REGN10933." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "1.1 fold drop in IC50 of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The K417N mutation decreased the affinity ~4 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs)" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs)" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C682, and to a lesser extent C614 and C660" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against IgG1 monoclonal antibody ab1." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.86 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~6x binding against this isolated mutation. Estesevimab lost ~100x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 7.5 fold decrease in KD value for antibody binding of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 1.5 fold decrease in KD value of antibody binding of ACE2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 3-fold decrease in affinity compared to wild-type RBD on the cell surface (Kd = 145.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection, Two-tailed Wilcoxon matched-pairs signed-rank test shows mild resistance P=0.0361." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 36.9 fold decrease in KD value for antibody binding of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "27% of 44 early pandemic exposure convalescent plasma/sera lose all activity against a RBD triple mutant pseudovirus (RBD mutatants of the 501Y.V2 ""South African"" lineage), while only 23% retained high titres" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of the B.1.351 RBD variants for ACE2 increased by 3.7 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.4-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.351 key variants lentivirus. Compare to 8.8-fold reduction against cultured B.1.351 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from B.1.351." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26)." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26)." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.351 and P.1 samples showed average Ct cycle threshold of 22.2 vs 23 for wildtype (i.e. ~60% higher viral load) comparing 3360 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibodies ab8 and IgG1 ab1. Complete loss for the same antibodies was also observed against S1 pseudotyped and full Spike protein trimers with both B.1.351 and P.1 lineage variants, with slight binding signal for P.1 against IgG1 at the highest concentration tested (1uM). Complete loss of neutralization by these two antibodies was also observed." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This combination showed ~3x increase binding to ACE2 vs wild type, about half that of the B.1.1.7 lineage, suggesting that the K417N mutation is slightly detrimental to ACE2 binding, probably as a result of disrupting the salt bridge formed with ACE2 residue D30" "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Moderna vaccinee sera, 2.7x reduction in neutralization, and 6.4 for the full B.1.351 Spike mutation complement, but despite the observed decreases, titers in human vaccinee sera against the B.1.351 variant remained at clinically significant level of ~1/300." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.01.25.427948" "doi:10.1101/2021.01.25.427948" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "36,590 variant-specific RT-PCR tests were performed on samples collected between April 12 and May 7, 2021 in France to compare variant spread. Compared to January to March 2021, B.1.351 variant had a significant transmission advantage over B.1.1.7 in some regions (15.1 to 16.1% in Île-de-France and 16.1 to 18.8% in Hauts-de-France). This shift in transmission advantage is consistent with the immune evasion abilities of B.1.351 and the high levels of immunization in these regions." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.05.12.21257130" "doi:10.1101/2021.05.12.21257130" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure." "" "" "" "Pearson" "2021" "https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant of key B.1.351 lineage mutations showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure." "" "" "" "Pearson" "2021" "https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Average ~10-fold reduction in neutralization efficacy in convalescent sera of 16 health workers infected in Spring 2020." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) with enrollment June 24 and November 9, 2020 from ~2000 HIV-negative 18-64 year olds (1:1 placebo to treatment), incidence of serious adverse events 14 or more days post- 2nd dose was balanced between the vaccine and placebo groups. A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed 3.5x reduction in neutralization (ID50) for B.1.351 RBD pseudotype HIB-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a similar 3.2x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 2 (B.1.351) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolished neutralization by mAbs CQ026 and CQ038, greatly diminished neutralization by CQ012 and CQ046." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23041,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trachea viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~750x fold drop in the R3P1-E4 antibody in comparison to the IgG control." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23041,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Lung viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~2266x fold drop in the R3P1-E4 antibody in comparison to the IgG control." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23041,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "100% of the 5 8‑month‑old male R3P1-E4 antibody treated mice suvived 14 days after infection while only 60% the control group mice survived 5 days post infection." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~5x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied]" "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (no synergy as level approx. that of N501Y alone)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 57.1 fold decrease in KD value for antibody binding of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.64 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 1.1 fold decrease in KD value of antibody binding of ACE2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.25 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 antibody C682" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The K417T mutation decreased the affinity ~2 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~16x binding against this isolated mutation. Estesevimab lost ~16x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 2.9 fold decrease in KD value for antibody binding of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "2.6 fold increase in IC50 of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,23012,23060,23061,23062,23063" "K417T,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from P.1." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,23012,23060,23061,23062,23063" "K417T,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of the P.1 RBD variants for ACE2 increased by 5.3 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The KD for the pseudotyped P.1-ACE2 interaction is 4.8 nM, showing that binding to P.1 is essentially indistinguishable from B.1.351 (4.0 nM), which binds with ~19x greater affinity that wild type." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22851" "T430I" "NC_045512.2:g.1289C>T" "YP_009724390.1:p.Thr430Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22865" "A435S" "NC_045512.2:g.1303G>T" "YP_009724390.1:p.Ala435Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb H014 (on D614G background)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The N440K variant produced ten times higher infectious viral titers than a prevalent A2a strain, and over 1000 folds higher titers than a much less prevalent A3i strain prototype in Caco2 cells. Interestingly, A3i strain showed the highest viral RNA levels, but the lowest infectious titers in the culture supernatants, indicating the absence of correlation between the RNA content and the infectivity of the sample." "" "" "" "Tandel" "2021" "https://doi.org/10.1101/2021.04.30.441434" "doi:10.1101/2021.04.30.441434" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 0.7x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "N501Y substitution decreased the neutralizing and binding activities of CB6 and increased that of BD-23" "" "" "" "Cheng" "2021" "https://doi.org/10.1186/s12985-021-01554-8" "doi:10.1186/s12985-021-01554-8" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 45% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, eliminated in subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 3 antibody C669 mildly selected for the emergence of the N440K mutation in vitro (in contrast to N440H which caused mild escape in Class 1/2 mAb C653)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882,23399,23401,23402,23403" "N440K,N440K,N440K,N440K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "A 47yo Indian male was reinfected with B.1.36 lineage virus in September 2020 after infection with genetically distinct B.1.36 virus in July, with negative PCR tests in between. While the forst episode was asymptomatic, the second included fever, cough, and malaise. The second case additionally contained stopgain ORF3a:E261*" "" "" "" "Rani" "2021" "https://doi.org/10.1002/jmv.26997" "doi:10.1002/jmv.26997" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444T" "NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444R" "NC_045512.2:g.1331A>G" "YP_009724390.1:p.Lys444Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Identified in 6/20 replicates of recombinant VSV growth in the presence of mAb COV2-2130." "" "" "" "Dong" "2021" "https://doi.org/10.1101/2021.01.27.428529" "doi:10.1101/2021.01.27.428529" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444T" "NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Results in 3.7-fold drop in neutralization potency for COVA2-29, which is a cluster I RBD141 specific antibody." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444R" "NC_045512.2:g.1331A>G" "YP_009724390.1:p.Lys444Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 20% of supernatant sequences) under two rounds of COV-NY convalescent plasma passage, eliminated in rounds three and four" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444T" "NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolishes binding efficiency vs wild type for mAb REGN10933." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 14% of supernatant sequences) after COV-NY convalescent plasma assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Improvement in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-01 and moderately resistant to 2H04 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22896" "V445A" "NC_045512.2:g.1334T>C" "YP_009724390.1:p.Val445Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 41% appearance in 2 passages against Regeneron monoclonal antibody RGN10987 @ 10ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2499 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 1 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed a ~4x drop in sensitivity." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-02, SARS2-32 and SARS2-35 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Decrease in neutralization capability of all 4 convalescent sera tested (1 ablated)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations), triple replicates. Against a broader panel of 16 convalescent plasma (no replicates), reductions in neutralization are considerably less dramatic in pattern, and sometime neutralization increases." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 95% appearance in 2 passages against Regeneron monoclonal antibody RGN10934 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 4 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Most effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-07 nd moderately resistant to SARS2-16 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910,23012,23039,23040,23373,25046" "N450D,N450D,E484K,Q493R,Q493R,T604I,P1162S" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1811C>T,NC_045512.2:g.3484C>T" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Thr604Ile,YP_009724390.1:p.Pro1162Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22905" "N448S" "NC_045512.2:g.1343A>G" "YP_009724390.1:p.Asn448Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22907" "Y449H" "NC_045512.2:g.1345T>C" "YP_009724390.1:p.Tyr449His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22907" "Y449N" "NC_045512.2:g.1345T>A" "YP_009724390.1:p.Tyr449Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912,22916" "L452M,L452M" "NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A" "YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912,22916" "L452M,L452M" "NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A" "YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.67 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Observed ~2x decrease on average in neutralization efficacy in convalescent sera of 16 health workers." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 3 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2/3 antibody C628 and class 2 antibody C643 selected for the emergence of the L452R mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Ablation of neutralization capability of 3 of 4 convalescent sera tested, the other is significantly hindered." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~1.7-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "10 of 14 RBD-specific mAbs that showed at least 10-fold reduced neutralization of B.1.427/B.1.429 variant pseudotype (S13I, W152C, and L452R) were also found to poorly bind to just a L452R RBD mutant, demonstrating a role for this mutation as an escape mechanism for certain RBD-targeting mAbs." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "L452R derivative virus did not induce IFN-gamma expression even at the highest concentration tested (10 nM) in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456)." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We observed increased entry by pseudoviruses carrying the L452R mutation compared to D614G alone, with a 6.7 to 22.5-fold increase in 293T cells and a 5.8 to 14.7-fold increase in human airway organoids." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.32 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02." "" "" "" "Motozono" "2021" "https://doi.org/10.1016/j.chom.2021.06.006" "doi:10.1016/j.chom.2021.06.006" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs X593 and P2B-2F6" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. [listed as L454R in Figure, but L452R in text, also text suggests not statistically significant, but error bars say otherwise in Figure 4]" "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. L452R conferred about a two-fold reduction in neutralisation by vaccine sera, but was not statistically significant with this sample size." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~5x binding against this isolated mutation. Cligavimab lost ~4x binding against this isolated mutation. Regdanvimab lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-02 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Increased stability of RBD expression in yeast, suggesting increased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012" "L452R,L452R,L452R,E484K" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant combination shows a ~4-5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, same as L452R alone." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012" "L452R,L452R,L452R,E484Q" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484Q had a ~5x drop in neutralization (vs ~10x for E484K). When E484Q and L452R were combined, the fold change was significant, but similar to that of L452R alone (~2x), suggesting no evidence for an additive effect [perhaps even E484Q effect dilution]." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617) showed a 1.22x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2.5x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617) showed a 1.30x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.18x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x drop in neutralization (NT50) [working with the delins, less than just L452R but more than just E484Q]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x infectivity advantage to the spike particles [less than L452R or E484Q alone working with the delins]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Pseudotyped viruses for B.1.617 was 2.3-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. [details on the convalescent patient sera collection are not abundantly clear in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617) showed a 1.85x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The combination caused a 3-fold increase in infectivity relative to D614G wild type. [compare to 3.5x for L452R alone]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604" "L452R,L452R,L452R,E484Q,P681R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Gross examination of 3+3 hamster lung specimens showed pronounced congestion and hemorrhages on days 5 and 7 post-infection in the case of the B.1.617.1 as compared with the B.1. The lung lesions with the B.1 variant were minimal to mild whereas with B.1.617.1 they were moderate. For B.1 pneumonic changes were minimal to mild (inflammatory cell infiltration, focal consolidation and mild congestion). The pronounced changes (moderate to severe) with mononuclear infiltration in the alveolar interstitial space, interstitial septal thickening, consolidation and pneumocyte hyperplasia were observed with B.1.617.1 variant consistently." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.05.05.442760" "doi:10.1101/2021.05.05.442760" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604" "L452R,L452R,L452R,E484Q,P681R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In 9 infected hamsters each for B.1 and B.1.617.1, no significant change in viral load or subgenomic RNA levels were detected." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.05.05.442760" "doi:10.1101/2021.05.05.442760" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604" "L452R,L452R,L452R,E484K,P681R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant combination shows a ~3x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, significantly less of a decrease than any B.1.617 lineage variants alone, suggesting a synergistic effect on cell entry while maintaining known immunity esacpe mutants." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,P681R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Normalized for particle number, on ACE2.293T cells showed that the B.1.617 spike protein was >2-fold increase in infectivity relative to D614G wild type." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23060,23061,23062,23063" "L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of these B.1.417/B.1.429 defining variants in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The L452R mutation increased the infectivity more than two-fold in these conditions." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 7.42x drop in neutralization (NT50) [mostly from 3 of the sera]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this RBD mutation conferred a 2.36x drop in neutralization (NT50)." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~2x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 583 test-positive were Epsilon. Two dose vaccine efficacy against Epsilon was 97.6 (90.2-99.4%), one dose VE was 76.3 (48.1-89.1%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917" "L452Q" "NC_045512.2:g.1355T>A" "YP_009724390.1:p.Leu452Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917" "L452Q" "NC_045512.2:g.1355T>A" "YP_009724390.1:p.Leu452Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.27 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 3.4x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.038x fold change in IC50 in C.37 Lambda" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 1.7x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.048x fold change in IC50 in C.37 Lambda" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "VSV pseudotyped with Y453F reduced inhibition by most of the 13 potent convalescent serum/plasma samples tested, albeit with variable efficiency (median increase of serum/plasma titer required for 50% neutralization [NT50] = 1.62x, range = 1.02x to 3.43x), indicating that this RBD mutation may compromise SARS-CoV-2 control by preexisting neutralizing antibody responses." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.celrep.2021.109017" "doi:10.1016/j.celrep.2021.109017" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.25 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "10-fold reduction in binding efficiency vs wild type for MAb REGN10933." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~12x binding against this double mutation. Casirivimab lost ~64x binding against this double mutation. Cligavimab lost ~6x binding against this double mutation. Estesevimab lost ~10x binding against this double mutation. Imdevimab lost ~5x binding against this double mutation. Regdanvimab lost ~8x binding against this double mutation. Sotrovimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed in 4 separate mink farms in Denmark, and Y453F is circulating relatively widely in humans." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02." "" "" "" "Motozono" "2021" "https://doi.org/10.1016/j.chom.2021.06.006" "doi:10.1016/j.chom.2021.06.006" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "The induction level of IFN-gamma expression by the Y453F derivative in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456) was significantly lower." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "" "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Casirivimab lost >50x binding against this mutation." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.celrep.2021.109017" "doi:10.1016/j.celrep.2021.109017" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "Y453F,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.1358A>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "The so-called ""delta F"" variant combination previously observed in mink spillover events also emerged in a lymphoma patient (non-Hodgkin diffuse B-cell lymphoma IV stage B) with a long-term COVID-19 infection (4 months) where 18 de novo mutation occureed overall. Patient was taking rituximab, the B-cell-depleting agent, and had no detectable neutralizing antibody response." "" "" "" "Bazykin" "2021" "https://virological.org/t/emergence-of-y453f-and-69-70hv-mutations-in-a-lymphoma-patient-with-long-term-covid-19/580" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22924,22925,22926" "L455S,L455S,L455S" "NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C" "YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.45 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22926,22927,22927,22928,22930,22930" "F456L,F456L,F456L,F456L,F456L,F456L" "NC_045512.2:g.1366T>C,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>A,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>G,NC_045512.2:g.1368T>A" "YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This double substitution reduces neutralization by RBD-specific mAbs from different clusters, specifically, the cluster I mAb COVA2-29, cluster III mAb COVA2-07 and cluster VI mAb COVA1-12. For COVA1-12 all neutralization activity is abolished, while COVA2-07 activity is just below the level required to calculate an IC50 value." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Moderate in vitro selection against class 1 (Spike 'up' conformation) antibodies C683 and C664. Unclassified antibody C666 selected for the emergence of the F456V mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22936" "K458N" "NC_045512.2:g.1374G>T" "YP_009724390.1:p.Lys458Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.09 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460Y" "NC_045512.2:g.1378A>T" "YP_009724390.1:p.Asn460Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mild escape mutant emergent for class 1 antibody C613 in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22941" "N460I" "NC_045512.2:g.1379A>T" "YP_009724390.1:p.Asn460Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22941" "N460S" "NC_045512.2:g.1379A>G" "YP_009724390.1:p.Asn460Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22964" "I468V" "NC_045512.2:g.1402A>G" "YP_009724390.1:p.Ile468Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22964" "I468V" "NC_045512.2:g.1402A>G" "YP_009724390.1:p.Ile468Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22976" "I472V" "NC_045512.2:g.1414A>G" "YP_009724390.1:p.Ile472Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22976" "I472V" "NC_045512.2:g.1414A>G" "YP_009724390.1:p.Ile472Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb X593 (on D614G background)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C102, C105 and C144 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~50x binding against this isolated mutation. Estesevimab lost ~8x binding against this isolated mutation. Sotrovimab lost ~30x binding against this isolated mutation. Tixagevimab lost ~15x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some class 1 (Spike 'up' conformation) antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 host variant dependency" "" "" "This mutation's measured interaction affinity with ACE2:p.S19P (0.03% minor allele frequency, found almost exclusively in African/African-Americans in the GnomAD database) was significantly lower than the predicted value, indicating that these mutations were not independent. This is consistent with the fact that the ACE2 residue S19 is adjacent to RBD residue S477 in the contact interface." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 2.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "While S477N itself is highly resistent to a broad range of monoclonal antibodies, combined with S514F high neutralization is restricted to only three antibodies in a broad screen." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of mild positive and negative changes in neutralization capability of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), 10 show low neutralization." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 11 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.22 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-07, SARS2-16 and SARS2-19 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility." "" "" "" "Singh" "2021" "https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows some resistence across all antibodies tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility." "" "" "" "Singh" "2021" "https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding, with increasing proportion in subsequent rounds." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-07 and SARS2-16 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,22995,23042" "T478K,T478K,S494P" "NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1480T>C" "YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Combination of RBD mutations appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome complicated by diffuse alveolar hemorrhage, who was receiving anticoagulation therapy, glucocorticoids, cyclophosphamide, and intermittent rituximab and eculizumab." "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23012" "S477N,E484K" "NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~10x binding against this double mutation. Tixagevimab lost ~16x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was neutralized slightly less than D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Compared to the clade 20A strains that predominated during phase 1 between March and May 2020, the Marseille-4 variant (characterized by this mutation plus N:p.M234I;A376T) was associated with a lower frequency of cough, rhinitis, and olfactory and gustatory disorders. By contrast, hypoxemia was more frequent in patients infected with the Marseille-4 variant." "" "" "" "Fournier" "2021" "https://doi.org/10.1016/j.ijid.2021.03.068" "doi:10.1016/j.ijid.2021.03.068" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "11 cases of re-infection with the ""Marseille-4"" variant found within 1028 positive tests, where all of the earlier infections were from different strains. This lineage is also characterized by N:p.M234I;A376T" "" "" "" "Fournier" "2021" "https://doi.org/10.1016/j.ijid.2021.03.068" "doi:10.1016/j.ijid.2021.03.068" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23003" "N481Y" "NC_045512.2:g.1441A>T" "YP_009724390.1:p.Asn481Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Minor variant in initial round of in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009" "V483L" "NC_045512.2:g.1447G>C" "YP_009724390.1:p.Val483Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, 1B07, SARS2-32, SARS2-35 and SARS2-07 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in all 4 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Remarkably, several of the E484 escape mutants were resistant to neutralization at the highest concentration (1:80 initial dilution) of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), all but one show major resistance." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 152 virus from a chronically infected patient: although mAb C1A-B12 had no activity against this pseudotype, all three affinity optimized versions were active; the antibody containing the most mutations, C1A-B12.3, was the most potent (IC50 <0.5 μg/mL)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 152 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 152 S pseudotype was resistant to neutralization." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This Spike pseudotype for Day 152 virus from a chronically infected patient was completely resistent to REGN10933." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous." "" "" "" "Braeye" "2022" "https://doi.org/10.1101/2022.05.09.22274623" "doi:10.1101/2022.05.09.22274623" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "3rd exposure to antigen by Delta (B.1.617.2) (n=24) breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a 3rd mRNA vaccine dose in individuals aged 21 –63 years, median age=30 years. Data collected 5.5 months after 2nd vaccination." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous." "" "" "" "Braeye" "2022" "https://doi.org/10.1101/2022.05.09.22274623" "doi:10.1101/2022.05.09.22274623" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In sera from 17 sero-positive blood donors, and 18 months post-infection (May 2020) sera from 17 health care workers in Sweden, a 40x drop in neutralization by Omicron (B.1.1.529) pseudotyped lentivirus was observed in HEK293T cells using the First WHO International Standard (20/136). Median IC50 reduction was ~6x for the blood donors, and ~4.5x for the health care workers." "" "" "" "Sheward" "2021" "https://drive.google.com/file/d/1CuxmNYj5cpIuxWXhjjVmuDqntxXwlfXQ/view" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23071,23074,23075,22992,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,Y505H,Y505H,Y505H,S477N,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1430G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using molecular dynamics simulation, ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations." "" "" "" "Zhang" "2022" "https://doi.org/10.1101/2022.06.05.493249" "doi:10.1101/2022.06.05.493249" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "The only mutation in the B.1.351 lineage that appears to contribute to neutralization reduction (~1.7x across 10 convalescent sera from April 2020 infectees)" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 15/20 convalescent sera was significantly lower against this pseudotyped virus model" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2 antibodies C627, C602, C671, C643, and class 2/3 antibody C603 selected for the emergence of the E484K mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.3x reduction in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers of non-human primate sera after one or two doses of Ad26.COV2.S (Jannsen vaccine) against the variants containing the E484K substitution in the RBD were present but reduced (fold reduction between 3.35–7.78, 95% confidence interval all above twofold difference, one-sample t test)." "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-02, 1B07, SARS2-16, SARS2-32, SARS2-35 and 2B04 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Multiple individuals in two related households were infected with a newly acquired E484K mutation within the B.1.311 lineage. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient's quarantine period." "" "" "" "Sabin" "2021" "https://doi.org/10.1101/2021.10.02.21264415" "doi:10.1101/2021.10.02.21264415" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Of 50 mAbs tested, major loss of neutralization observed for S2N28, S2X615, S2N12, S2X192, S2H7, S2X16, S2X58, S2H70, S2X613, S2D19, S2N22, S2D32, S2H58, S2M11, S2D106, S2X30." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Monoclonal antibodies 13G9 and 58G6 maintain fairly high neutralization potency, compared to others interfacing with E484K." "" "" "" "Li" "2021" "https://doi.org/10.1101/2021.04.19.440481" "doi:10.1101/2021.04.19.440481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Analyzing responses to the E484K mutation seen in B.1.351 and P.1 variants, we noted that it did not fall in a region predicted to bind the HLAII alleles tested (table S4). The mutation appeared to have no substantial or differential impact on T cell responses." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Human sera from 5 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) neutralized this variant 3.4x less relative to reference USA-WA1/2020 strain. 8 convalescent plasma with weak IgG ELISA titre neutralized this variant 2.4x less relative to reference USA-WA1/2020 strain. One plasma failed to neutralize at all. 11 convalescent plasma with moderate IgG ELISA titre neutralized this variant 4.2x less relative to reference USA-WA1/2020 strain. 11 convalescent plasma with high IgG ELISA titre neutralized this variant 2.6x less relative to reference USA-WA1/2020 strain." "" "" "" "Jangra" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~20x binding against this isolated mutation. Casirivimab lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484K conferred a ten-fold reduction in neutralisation by vaccine sera." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~16x binding against this isolated mutation. Casirivimab lost ~16x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 3 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, E484Q shows a notably resistant profile, comparable to or even more resistant than E484K at later time points (i.e. more resistant to immune cell somatic mutation evolution), see Figure 5a,b. Subject C 32 days post-infection showed >>10 fold reduction in neutralization, reducing to ~10-fold by day 104. Subject B 26 days post-infection showed ~10 fold reduction in neutralization, reducing to ~4x at day 113. Notably, Subject B also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 32, and no E484K immune escape at day 104. Subject I 26 days post-infection showed ~10 fold reduction in neutralization, with no reduction in escape at day 102. Notably, Subject I also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 26, and no E484K immune escape at day 102." "" "" "" "Greaney" "2021" "https://doi.org/10.1016/j.chom.2021.02.003" "doi:10.1016/j.chom.2021.02.003" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in all 4 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Individual variants appearing at <=30% frequency at day 21 in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then appearing all at >95% frequency at day 27." "" "" "" "Chen" "2021" "https://doi.org/10.1101/2021.04.08.21254791" "doi:10.1101/2021.04.08.21254791" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.6 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported moderate increase in affinity compared to wild-type RBD on the cell surface (Kd = 38.5nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "E484K pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed a mean 2.8x decrease in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">20% (ELISA significance threshold) drop in antibody binding by this variant against monoclonal antibody VH-Fc ab8." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a 10x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus)" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody VH-Fc ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus)" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, ELISA tests show 10x reduced efficacy of a majority of isolated antibodies, but only a modest decrease for vaccine plasma overall." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "As measured by surface plasmon resonance, RBD with the E484K mutation alone showed a mean 19.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "This mutation occurred in 100% of sequenced virions after 12 passages and led to a 4-fold decrease in convalescent plasma neutralization activity" "" "" "" "Andreano" "2020" "https://doi.org/10.1101/2020.12.28.424451" "doi:10.1101/2020.12.28.424451" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in binding efficiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape due to E484K [given Dec 2020-Apr 2021 time frame of the study, this is assumed to entail both Beta and Gamma lineages]." "" "" "" "Chung" "2021" "https://doi.org/10.1136/bmj.n1943" "doi:10.1136/bmj.n1943" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22597,22599" "E484K,R346K,R346K" "NC_045512.2:g.1450G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E484K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22810,22811,22812,22813,22813" "E484K,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~32x binding against this double mutation. COR-101 lost ~160x binding against this double mutation. Casirivimab lost ~16x binding against this double mutation. Estesevimab lost ~32x binding against this double mutation. Regdanvimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~13x more infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22810,22811,22812,22813,22813,23399,23401,23402,23403" "E484K,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Approximately as infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of the individual variants)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23053,23054,23055,23060,23061,23062,23063" "E484K,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.4 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.5 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.4 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~17.5x folds more significant in 9 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Values taken 28 days after booster dose was given for BBIBP-CorVvaccine to 390 participants with 130 participants in the 0-14d-10m, 0-21d-10m and 0-28d-10m group. The geometric mean titers (GMT) of neutralizing antibody in 0-28d-10m and 0-21d-10m group were significantly higher than 0-14d-10m group at month 3, month 6 and month 10 after the second dose. A sharply decrease by 4.85-fold (GMT: 94.4-20.3), 4.67-fold (GMT: 134.4-28.8) and 4.49-fold (GMT: 145.5-32.4) was observed from day 28 to month 10 after the second dose in 0-14d-10m, 0-21d-10m and 0-28d-10m group, respectively, and they had similar decline kinetics." "" "" "" "Yao T" "2022" "https://doi.org/10.1101/2022.06.22.22276690" "doi:10.1101/2022.06.22.22276690" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Omicron neutralizing antibodies is 0.686x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~100x folds more significant in 3 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Viral load from oral swabs from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Viral load from lung tissue from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)]" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)]" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Protection against symptomatic infection caused by Beta/Gamma (assumed by combined presence of N501Y and E484K) was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%)." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Omicron neutralizing antibodies is 0.722x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 20 sera from BNT162b2 mRNA vaccine inoculated participants, 6 displayed mild (2x) reductions in neutralization. This variant combination showed the highest reduction, but the magnitude of the differences was small compared to the >4x differences in HA-inhibition titers that have been used to signal potential need for a strain change in influenza vaccines." "" "" "" "Xie" "2021" "https://doi.org/10.1038/s41591-021-01270-4" "doi:10.1038/s41591-021-01270-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In the case of VOC B.1.1.7+E484K, the addition of the E484K mutation to N501Y further increased the affinity, to ~15 fold higher than WT RBD (KD ~5 nM), by further increasing the k(on) as measured by surface plasmon resonance. Because the higher k(on) could result in mass transfer limiting binding, we confirmed that the kinetic measurement for this variant was not substantially affected by varying levels of immobilization." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.0015x fold change in IC50 in B.1.1.529 Omicron" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.025x fold change in IC50 in B.1.1.529 Omicron" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Omicron Molnupiravir (MK-4482) had no statistically significant change." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.5 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~11x, Vero ~10x, and Calu-3 ~11x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~12x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of 501 and 484)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied]" "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Pseudotyped viruses for B.1.618 was 2.5-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. [details on the convalescent patient sera collection are not abundantly clear in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, RBD-specific mutation E484Q did not significantly confer infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 1.34x drop in neutralization (NT50) [mostly from a single serum]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.618 was 2.7-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 3-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~4x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The estimated vaccine effectiveness against R.1 strain SARS-CoV-2 infection among residents in a Kentucky skilled nursing facility was 66.2% (95% CI = 40.5%–80.8%) and among health care workers was 75.9% (95% CI = 32.5%–91.4%) in the cohort of only those 14d+ post-vaccination Pfizer booster dose. VE against symptomatic COVID-19 was 86.5% (95% CI = 65.6%–94.7%) among residents and 87.1% (95% CI = 46.4%–96.9%) among HCP. VE against hospitalization was 94.4% (95% CI = 73.9%–98.8%) among residents; no HCP were hospitalized. Three residents died, two of whom were unvaccinated (VE = 94.4%; 95% CI = 44.6%–99.4%)." "" "" "" "Cavanaugh" "2021" "https://doi.org/10.15585/mmwr.mm7017e2" "doi:10.15585/mmwr.mm7017e2" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs]" "" "" "" "Sapkal" "2021" "https://doi.org/10.1101/2021.04.30.441559" "doi:10.1101/2021.04.30.441559" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs]" "" "" "" "Sapkal" "2021" "https://doi.org/10.1101/2021.04.30.441559" "doi:10.1101/2021.04.30.441559" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the P.1 & P.2 lineages of SARS-CoV-2 in Brazil. The Brazilian arm of the Phase 3 double blind study showed severe/critical disease VE of 81.9% (95% CI: 17.0-98.1), and moderate to severe/critical disease VE of 66.2% (95% CI: 51.0-77.1). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 69.3% of mostly severe infections sequenced as of this report, 69.4% were of P.2 lineage [defining lineage SNPs reported here]." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped P.2 virus has reduced neutralization activity vs wild type: 5.8x (30 sera Pfizer median 9 days post 2nd dose) and 2.9x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed in 4 separate mink farms in Denmark, but not humans, potential adaptation (diff set of farms than N501T)." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutation causes a greater than 100x fold change in IC50 of Ensovibep." "" "" "" "Rothenberger" "2021" "https://doi.org/10.1101/2021.02.03.429164v4" "doi:10.1101/2021.02.03.429164v4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutation causes a greater than 100x fold change in IC50 of Ensovibep." "" "" "" "Rothenberger" "2021" "https://doi.org/10.1101/2021.02.03.429164v4" "doi:10.1101/2021.02.03.429164v4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "IC50 relative to wildtype drops ~8x in neutralization efficiency between 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 1 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">60% drop in antibody binding (ELISA) by this variant against monoclonal antibody VH-Fc ab8." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 5 antibodies." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.13 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-07, SARS2-19, 1B07, SARS2-16 and 2B04 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed striking resistance with only 38% neutralization at the highest concentration tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Modest decrease in in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23023" "N487K" "NC_045512.2:g.1461T>G" "YP_009724390.1:p.Asn487Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, high ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Based on structural modelling, this change detected on day 128 sequencing in a chronically infected patient would alter an extensive network of polar interactions with antibody residue R94VH, a germline antibody residue that is conserved in all of the potent VH3-53/3-66-derived antibodies isolated from a convalescent donor 5 weeks after infection." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.11 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-32." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 3 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2/3 mAb C603 modestly selected for the emergence of this mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (3 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23063" "Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This Spike pseudotype for Day 146 virus from a chronically infected patient was completely resistent to REGN10933. The variant had a 4-fold decrease in REGN10987 neutralization sensitivity (2nd component of the Regeneron mAb cocktail)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23063" "Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 146 virus from a chronically infected patient: resistant to neutralization by mAb C1A-B12, and was still resistant to the affinity enhanced antibodies derived from it (i.e. no affinity maturation effect on neutralization)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23063" "Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 146 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 146 S pseudotype was resistant to neutralization." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490V" "NC_045512.2:g.1468T>G" "YP_009724390.1:p.Phe490Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) resistant to 3 individual sera at >4x" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs X593, 261-262, H4, and P2B-2F6" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 23% of supernatant sequences) after C121 monoclonal antibody assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in binding efficiency vs wild type for mAbs CB6/LY-CoV16 and LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2 mAb C627 modestly selected for the emergence of this mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Dominant (70%) in day 21 of prolonged infection in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then nearly disappearing (<5%) by day 27." "" "" "" "Chen" "2021" "https://doi.org/10.1101/2021.04.08.21254791" "doi:10.1101/2021.04.08.21254791" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 2 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, S484P shows a slightly resistant profile across both timepoints (i.e. resistant to immune cell somatic mutation evolution)" "" "" "" "Greaney" "2021" "https://doi.org/10.1016/j.chom.2021.02.003" "doi:10.1016/j.chom.2021.02.003" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-01 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Minor variant selected in late rounds of an in vitro evolution experiment for ACE2 binding. Shown to increase the thermostability but decrease the association rate constant of the RBD to ACE2" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using molecular dynamic simulation, the mildly (~1kcal/mol) enhanced binding energy of this variant is primarily contributed by Tyr505 (−4.98 kcal/mol) which is now involved in a strong hydrogen bonding network with Arg393. Another important energetic contribution comes from the altered orientation of Tyr41 which is now involved with two hydrogen-bonding interactions with Asp355 and Thr500." "" "" "" "" "2021" "https://doi.org/10.1016/j.bbrc.2021.01.035" "doi:10.1016/j.bbrc.2021.01.035" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Regdanvimab lost ~32x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23048" "G496S" "NC_045512.2:g.1486G>A" "YP_009724390.1:p.Gly496Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23053,23054,23055,23060,23061,23062,23063" "Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. The extent of affinity increase with Q498R and N501Y is not exactly quantified, as E484K always emerged with this duo during in vitro evolution." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome" "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~8x binding against this isolated mutation. Regdanvimab lost ~6x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "Variant within the six key residues in the receptor binding domain (RBD). Independently reported in UK, Australia (same origin as UK), and South Africa (independent origin)." "" "" "" "Flores-Alanis" "2021" "https://doi.org/10.3390/pathogens10020184" "doi:10.3390/pathogens10020184" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C663, and to a lesser extent C613." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Utilizing shark derived vnarbodies, S375F mutation on Omicron RBD disrupts the structure of β-strand, which inhibits binding with 20G6. 20G6 binds to a hidden epitope on RBD which is highly conserved in sarbecoviruses." "" "" "" "Feng" "2022" "https://doi.org/10.1002/smtd.202200387" "doi:10.1002/smtd.202200387" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.2x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 and day 14 post-2nd dose) against a recombinant single variant virus (modified replicating WA-1 cDNA clone) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.69 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape by lineage Alpha [defined here as N501Y positive, but E484K negative]." "" "" "" "Chung" "2021" "https://doi.org/10.1136/bmj.n1943" "doi:10.1136/bmj.n1943" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In 30 samples collected 111 to 260 days post onset of symptoms, the covalescent plasma can neutralize both the reference USA-WA1/2020 strain and the mouse adapted strain that contains the N501Y spike mutation with similar efficiency." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The N501Y mutation had the biggest effect on ACE2 affinity of any VOC mutation tested, increasing the affinity ~10 fold to KD ~7 nM, by increasing the k(on) ~1.8 fold and decreasing the k(off) by ~ 7 fold as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a modest decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Human sera from 6 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) can neutralize both the reference USA-WA1/2020 strain and the mouse adapted SARS-CoV-2 strain that contains the N501Y spike mutation with similar efficiency." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "As measured by surface plasmon resonance, RBD with the N501Y mutation alone showed a mean 2.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x)" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation alone accounts for most of the increased infectivity of the Alpha variant, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters, and Vero E6 (NHP) and Calu-3 (human) cell lines." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.03.08.434499" "doi:10.1101/2021.03.08.434499" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Lowered the neutralization potency of mAb COVA1-12 to the limit of the assay. Decrease in potency was observed against the N501Y pseudotype for the cluster IX mAb COVA2-17." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Vaccinated, but not post-infection sera, show decreased average T cell response to an N501Y peptide. When we primed transgenic mice expressing human HLA-DRB1*0401 with the Wuhan Hu-1 peptide pool, T cell responses to the B.1.1.7 variant peptide pool were significantly reduced (p = 0.0286). Furthermore, the T cell response to the spike N501Y mutation common to all three of the current VOC was ablated." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In silico methods (PyMOL and PDBePISA) involving mutagenesis (N501Y mutation) and interface analysis focusing on the Spike RDB-ACE2 interaction showed that the SARS-CoV-2 N501Y mutant (lineage B.1.1.7) establishes a more significant number of interactions relating to the mutant residue Y501 (Spike RDB) with residues Y41 and K353 (ACE2). This finding shows that the increased infectivity of SARS-CoV-2 lineage B.1.1.7 is associated with the interaction force between the Spike RBD Y501 mutant residue with the ACE2 receptor, which in this strain is increased." "" "" "" "" "2021" "https://doi.org/10.1101/2020.12.29.424708" "doi:10.1101/2020.12.29.424708" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Of 50 mAbs tested, major loss of neutralization observed for S2X128, S2D8, S2X192, S2D19, S2H14, S2H19." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x)" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Contrary to other reports on N501Y containing lineages (i.e. with additional mutations), N501Y alone may have an even greater affinity for a human monoclonal antibody specific for wild type. These results suggest that the individual N501Y mutation does not contribute to altered viral properties by itself, but may contribute to a collective conformational shift produced by multiple mutations." "" "" "" "Klegerman" "2021" "https://doi.org/10.1101/2021.04.26.441517" "doi:10.1101/2021.04.26.441517" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slightly increased infection rate amongst the cells. [in what is essentially a replicate experiment in the same paper, because each B.1.351 lineage variant was independetly evaluated and N501 is in both lineages, a significant decrease was observed, therefore the error bars described in this paper should be interpreted carefully]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The most frequent RBM mutation N501Y (165,519 instances) makes defective the atypical N-glycosylation sequon NGV 501-503, becoming a key RBM position for the interaction with hACE2-binding hotspot 353." "" "" "" "Gamez" "2021" "https://doi.org/10.1101/2021.04.09.439154" "doi:10.1101/2021.04.09.439154" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "0.7x reduction in neutralization by key variant in several variants of concern in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,22810,22811,22812,22813,22813" "N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~20x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~6x binding against this double mutation. M396 lost ~10x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,22810,22811,22812,22813,22813,23012" "N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In post-vaccination sera from individuals who received one (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) of the BNT162b2 Pfizer vaccine, an average 6.8x reduction in neutralization efficacy of this B.1.351 key variants pseudotype lentivirus vs D614G was observed." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,22810,22811,22812,22813,22813,23012" "N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "~7x reduction in neutralization by key B.1.351 lineage RBD variant combination in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Two of the cohort showed no neutralization against this variant." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23012" "N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~64x binding against this double mutation. COR-101 lost ~50x binding against this double mutation. Casirivimab lost ~250x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~32x binding against this double mutation. Tixagevimab lost ~10x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23271" "N501Y,N501Y,N501Y,N501Y,A570D" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Partial sequencing of S gene reveals two cases of probable early 2021 B.1.1.7 lineage reinfection from non-B.1.1.7 original cases in Lombardy, with 45 to 90 days between infections (less than the typical 90 day guideline for this call). Patients were 56 and 58yo, immunocompenent, with one a former smoker with obesity and dyslipidemia. One case required intubation during first infection, but presented with mild symptoms upon reinfection. The other case convalesced at home during the first episode, but required CPAP support in the subacute clinical unit upon reinfection." "" "" "" "Novazzi" "2021" "https://doi.org/10.1002/jmv.27066" "doi:10.1002/jmv.27066" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~9x, Vero ~8x, and Calu-3 ~8x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~13x, Vero ~10x, and Calu-3 ~10x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed no change in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H (""Ohio"") lineage was neutralized similarly to D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells for ACE2 affinity changes vs D614G alone, showing a ~70% drop in IC50 (i.e. increased affinity)." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23521,23522,23524,23525" "N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23071,23074,23075" "Y505H,Y505H,Y505H" "NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed first in a single tiger (cohort of 5), potential adaptation." "" "" "" "McAloose" "2020" "https://doi.org/10.1128/mBio.02220-20" "doi:10.1128/mBio.02220-20" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23071,23074,23075" "Y505H,Y505H,Y505H" "NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23102" "S514T" "NC_045512.2:g.1540T>A" "YP_009724390.1:p.Ser514Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23108" "E516Q" "NC_045512.2:g.1546G>C" "YP_009724390.1:p.Glu516Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23115" "L518Q" "NC_045512.2:g.1553T>A" "YP_009724390.1:p.Leu518Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23120" "A520S" "NC_045512.2:g.1558G>T" "YP_009724390.1:p.Ala520Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "CR3022 (SARS-targeting mAb) cross-reactivity lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23148" "K529T" "NC_045512.2:g.1586A>C" "YP_009724390.1:p.Lys529Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing statistically significant increased infection rate amongst the cells." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated that there is very little free energy change (ddG. -0.02 kcal/mol) for this variant (i.e. approx. same stability as wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant raises PIWAS epitope score from 3.6% to 6.2% (improved immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23373" "T604I" "NC_045512.2:g.1811C>T" "YP_009724390.1:p.Thr604Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a lentivirus virus pseudotyped with D614G Spike, sera from vaccinated individuals who received the second dose (9–11 days post-second dose of Pfizer) exhibited a robust neutralizing potential, with a mean NT50 value of 99,000. This was an average of a 2-fold increase, relative to sera drawn from the individuals who received one dose of vaccination—mean NT50 dilution of 51,300. Importantly, a 6-fold increase in mean NT50 dilution was obtained when sera from the first vaccination dose was compared to convalescent sera from cohort with severe disease (NT50 51,000 vs 8,700) 21 to 63 days post-onset." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 2.5 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to wild type, D614G showed increased infectivity (ie. cold stability) after storage at -20°C for up to 30 days." "" "" "" "Huang" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped D614G virus has reduced neutralization activity vs wild type: 1.2x (37 sera Pfizer median 9 days post 2nd dose, 37 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.05x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.45x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.43x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 1.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In four cell lines (including 293T-hACE2 cells), this mutation combination increases infectivity vs D614G alone" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation (a.k.a. ""Doug"") outside the receptor binding domain, while highly favorable to improved human-human transmission, decreases transduction in naked mole-rat (Heterocephalus glaber) fibroblast and Japanese pipistrelle bat (Pipistrellus abramus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Weissman" "2020" "https://doi.org/10.1101/2020.07.22.20159905" "doi:10.1101/2020.07.22.20159905" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 conferred a nearly two-fold infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD mutation conferred a 4.85x drop in neutralization (NT50)." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Weissman" "2020" "https://doi.org/10.1101/2020.07.22.20159905" "doi:10.1101/2020.07.22.20159905" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.35x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission." "" "" "" "Plante" "2020" "https://doi.org/10.1038/s41586-020-2895-3" "doi:10.1038/s41586-020-2895-3" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses." "" "" "" "Ozono" "2020" "https://doi.org/10.1038/s41467-021-21118-2" "doi:10.1038/s41467-021-21118-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses." "" "" "" "Ozono" "2020" "https://doi.org/10.1038/s41467-021-21118-2" "doi:10.1038/s41467-021-21118-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Studying 94 COVID-19 extended infection cases with genomics April 1 to October 17, 2020, one case developed 23 mutations in a 19 day period, including this combination in Spike." "" "" "" "Landis" "2021" "https://doi.org/10.1101/2021.05.08.21256775" "doi:10.1101/2021.05.08.21256775" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The increased transduction with Spike D614G ranged from 1.3- to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2 and from 1.5- to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction." "" "" "" "Daniloski" "2021" "https://doi.org/10.7554/eLife.65365" "doi:10.7554/eLife.65365" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.97x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a slight decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.53x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575" "D614G,D614G,D614G,D614G,L5F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.1x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575" "D614G,D614G,D614G,D614G,L5F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.23x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575" "D614G,D614G,D614G,D614G,L5F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664" "D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.526) showed a 1.02x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664" "D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.526) showed a 1.78x increase in binding (KD) relative to D614G, even though each variant independently decreases binding." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664" "D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.526) showed a 1.34x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600" "D614G,D614G,D614G,D614G,S13I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600" "D614G,D614G,D614G,D614G,S13I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.42x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600" "D614G,D614G,D614G,D614G,S13I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600,22018,22915,22916,22917" "D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. [Stark contrast to 2.15x increase in binding by convalescent plasma 8 months post infection, presumably via memory B cell affinity maturation against L452R effects] 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600,22018,22915,22916,22917" "D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.429 aka Epsilon) showed a 2.82x increase in binding (KD) relative to D614G, indicating a strong marginal effect for L452R." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600,22018,22915,22916,22917" "D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, indicating ablated marginal effect from L452R." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614" "D614G,D614G,D614G,D614G,L18F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.07x decrease in binding (KD) relative to D614G. Compare to increased binding in full Spike variant complements for major lineages containing this variant subset: 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614" "D614G,D614G,D614G,D614G,L18F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.66x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Compare to decreased binding in full Spike variant complements for major lineages containing this variant subset: 0.96x (B.1.351 aka Beta), 0.77x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614" "D614G,D614G,D614G,D614G,L18F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.30x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.28x increase (B.1.351 aka Beta), and 1.14x decrease (P.1 aka Gamma). 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.17x increase (B.1.351 aka Beta), and 1.47x decrease (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing P.1 aka Gamma) showed a 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing P.1 aka Gamma) showed a 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing P.1 aka Gamma) showed a 4.24x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664" "D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing B.1.351 aka Beta) showed a 1.04x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, in contrast to the largely positive binding values for each individual mutation that comprises the set." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664" "D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing B.1.351 aka Beta) showed a 1.28x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. It shows a 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664" "D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.351 aka Beta) showed a 3.56x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21621" "D614G,D614G,D614G,D614G,T20N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.39x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21621" "D614G,D614G,D614G,D614G,T20N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.96x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21621" "D614G,D614G,D614G,D614G,T20N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21638" "D614G,D614G,D614G,D614G,P26S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.58x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21638" "D614G,D614G,D614G,D614G,P26S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.23x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21638" "D614G,D614G,D614G,D614G,P26S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.33x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.51x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing B.1.1.7 aka Alpha) showed no change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.28x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing B.1.1.7 aka Alpha) showed a 1.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.1.7 aka Alpha) had 5.43x increased binding relative to D614G alone." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21801" "D614G,D614G,D614G,D614G,D80A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination showed no change relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21801" "D614G,D614G,D614G,D614G,D80A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.64x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.35x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21801" "D614G,D614G,D614G,D614G,D80A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21846" "D614G,D614G,D614G,D614G,T95I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21846" "D614G,D614G,D614G,D614G,T95I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21846" "D614G,D614G,D614G,D614G,T95I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21974" "D614G,D614G,D614G,D614G,D138Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21974" "D614G,D614G,D614G,D614G,D138Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21974" "D614G,D614G,D614G,D614G,D138Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.32x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22018" "D614G,D614G,D614G,D614G,W152C" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.15x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22018" "D614G,D614G,D614G,D614G,W152C" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22018" "D614G,D614G,D614G,D614G,W152C" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.03x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22132" "D614G,D614G,D614G,D614G,R190S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.59x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22132" "D614G,D614G,D614G,D614G,R190S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.82x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22132" "D614G,D614G,D614G,D614G,R190S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22206" "D614G,D614G,D614G,D614G,D215G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.19x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22206" "D614G,D614G,D614G,D614G,D215G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.79x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22206" "D614G,D614G,D614G,D614G,D215G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D253G,D253G,D253G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D253G,D253G,D253G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.08x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D253G,D253G,D253G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22810,22811,22812,22813,22813" "D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22810,22811,22812,22813,22813" "D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.76x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.75x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22810,22811,22812,22813,22813" "D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22812" "D614G,D614G,D614G,D614G,K417T" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.28x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22812" "D614G,D614G,D614G,D614G,K417T" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22812" "D614G,D614G,D614G,D614G,K417T" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.66x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.05x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.16x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 6.2-fold lower (95% CI: 11.8x-14.3x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 4.2x-fold lower (95% CI: 0.15x-0.20x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "paired testing of vaccine sera against ancestral virus compared to Omicron BA.1 shows that 3-dose vaccine regimen provides over 50x fold increase in protection against Omicron(B.1.1.529 [BA.1]) compared to a 2-dose regimen." "" "" "" "Hao" "2022" "https://doi.org/10.1101/2022.08.12.22278720" "doi:10.1101/2022.08.12.22278720" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 28.7x-fold lower (95% CI: 0.03x-0.05) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "4th antigenic exposure with Omicron (B.1.1.529 [BA.1])(n=29) infection increased variant specific plasma antibody and memory B cell responses as well as overall increased strain specific memory in individuals aged 22 –79 years, median age=33.5 years. Data collected 2.4 months after 3rd vaccination." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 3.4-fold lower (95% CI: 3.2x-3.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 3.9x-fold lower (95% CI: 0.14x-0.17x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 78fM for binding to the Omicron BA.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 4.5-fold lower (95% CI: 4.3x-4.7x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 4.2-fold lower (95% CI: 5.8x-6.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 3.9x-fold lower (95% CI: 0.14x-0.18x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23012" "D614G,D614G,D614G,D614G,E484K" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.42x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23012" "D614G,D614G,D614G,D614G,E484K" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23012" "D614G,D614G,D614G,D614G,E484K" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This variant appears twice in the experiments, with slightly different affinities (both ~1.2x decrease in binding relative to D614G) using flow cytometry and ACE2 ectodomains-Fc portion IgG complex." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23060,23061,23062,23063" "D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23060,23061,23062,23063" "D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23060,23061,23062,23063" "D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.52x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis). Compare to full Spike variant complements for major lineages containing this variant subset: 5.43x (B.1.1.7 aka Alpha), 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23271" "D614G,D614G,D614G,D614G,A570D" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23271" "D614G,D614G,D614G,D614G,A570D" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23271" "D614G,D614G,D614G,D614G,A570D" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.18x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23521,23522,23524,23525" "D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23521,23522,23524,23525" "D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.21x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23521,23522,23524,23525" "D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.48x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant change in virus neutralzation by 18 Pfizer two dose vaccinee sera compared to B.1.1.7. [results without including the used mutation A27S likely generalizable, as this is not a lineage defining mutation]" "" "" "" "Zuckerman" "2021" "https://doi.org/10.1101/2021.03.25.21253908" "doi:10.1101/2021.03.25.21253908" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.26x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23664" "D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23664" "D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23664" "D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed essentially no change in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23709" "D614G,D614G,D614G,D614G,T716I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.12x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23709" "D614G,D614G,D614G,D614G,T716I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23709" "D614G,D614G,D614G,D614G,T716I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.58x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24506" "D614G,D614G,D614G,D614G,S982A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24506" "D614G,D614G,D614G,D614G,S982A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.3x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24506" "D614G,D614G,D614G,D614G,S982A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24642" "D614G,D614G,D614G,D614G,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.69x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24642" "D614G,D614G,D614G,D614G,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.22x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24642" "D614G,D614G,D614G,D614G,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.56x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24914" "D614G,D614G,D614G,D614G,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24914" "D614G,D614G,D614G,D614G,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24914" "D614G,D614G,D614G,D614G,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.96x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23429" "A623T" "NC_045512.2:g.1867G>A" "YP_009724390.1:p.Ala623Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain increases the virus transduction rate in tree shrew (Tupaia belangeri), (as it does in humans) according to pseudotyped VSV experiments." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.87 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Six minks were intranasally infected with WA1 isolate, all developed this mutation during infection." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23587,23587" "Q675H,Q675H" "NC_045512.2:g.2025G>C,NC_045512.2:g.2025G>T" "YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly enhanced the ability of the pseudotyped VSV to infect fat-tailed gerbil (Pachyuromys duprasi) kidney cell cultures, with a transduction rate of 13.4%, close to the 15.7% in epithelial-like human Huh-7 cells while starting from a significantly lower wildtype (Wuhan-Hu-1 Spike VSVdeltaG psuedotype) rate." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681R" "NC_045512.2:g.2042C>G" "YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. [PG: Inferred by conservative AA substitution of described P681H]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic." "" "" "" "Johnson" "2020" "https://doi.org/10.1101/2020.08.26.268854" "doi:10.1101/2020.08.26.268854" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In the absence of N501Y, this Alpha lineage change in the furin clevage site did NOT show significant increase in infectivity relative to wild type, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.03.08.434499" "doi:10.1101/2021.03.08.434499" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry)." "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry)." "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing NO statistically significant infection rate change amongst the cells, suggesting that furin cleavage typically used for cell entry is not affected by this change one amino acid upstream of the RXXR recognition pattern." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 0.9x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic." "" "" "" "Johnson" "2020" "https://doi.org/10.1101/2020.08.26.268854" "doi:10.1101/2020.08.26.268854" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681R" "NC_045512.2:g.2042C>G" "YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). [Inference from similar positively charged substitution P681H actually described in the work]" "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "While the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC)." "" "" "" "Lubinski" "2021" "https://doi.org/10.1101/2021.04.06.438731" "doi:10.1101/2021.04.06.438731" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23399,23401,23402,23403" "P681R,D614G,D614G,D614G,D614G" "NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Quantification of the band intensities showed that the P681R mutation, which lies near the proteolytic processing site, caused a small increase in proteolytic processing as measured by a 2-fold decrease in the ratio of S/S2." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23664" "A701V" "NC_045512.2:g.2102C>T" "YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23664" "A701V" "NC_045512.2:g.2102C>T" "YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.33 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant increases PIWAS epitope score from 0.69% to 2.3% Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain showed a decreased capacity to transduce PK-15 (pig kidney, Sus scrofa) and PaKi (black flying fox kidney, Pteropus alecto) cell line cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed first in a single tiger (cohort of 5), potential adaptation." "" "" "" "McAloose" "2020" "https://doi.org/10.1128/mBio.02220-20" "doi:10.1128/mBio.02220-20" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. T716I was expressed at significantly lower level, accounting for the decreased infectivity of this spike protein. This property may be specific to spike protein biosynthesis in 293T cells and is not likely to reflect the situation in vivo given the reported increase in infectivity of the B.1.1.7 virus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23897" "Q779K" "NC_045512.2:g.2335C>A" "YP_009724390.1:p.Gln779Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 20% appearance in 2 passages against Regeneron monoclonal antibody RGN10989 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23948" "D796H" "NC_045512.2:g.2386G>C" "YP_009724390.1:p.Asp796His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Fatal COVID-19 complications in immunocomprimised patient after immune escape from convalescent plasma" "" "" "" "Kemp" "2020" "https://doi.org/10.1101/2020.12.05.20241927" "doi:10.1101/2020.12.05.20241927" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24000" "S813I" "NC_045512.2:g.2438G>T" "YP_009724390.1:p.Ser813Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb B38" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24077" "D839N" "NC_045512.2:g.2515G>A" "YP_009724390.1:p.Asp839Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry." "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24077" "D839Y" "NC_045512.2:g.2515G>T" "YP_009724390.1:p.Asp839Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry." "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24130" "N856K" "NC_045512.2:g.2568C>A" "YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch." "" "" "" "Lucaci" "2021" "" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24170" "I870V" "NC_045512.2:g.2608A>G" "YP_009724390.1:p.Ile870Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Appeared at same time as T478K,S494P but listed separately due to distance and different domains affected in the Spike (i.e. putatively an independent mutation from a functional standpoint since the former are from S1, the latter from S2)." "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24377,24378" "S939F,S939F" "NC_045512.2:g.2816C>T,NC_045512.2:g.2816C>T" "YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 6/20 convalescent sera was significantly lower against this single variant pseudotyped virus model, showing similar patterns to the pseudotyped virus model of B.1.1.7." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (70%) increase in infection rate amongst the cells, hence this individual variant is likely to significantly contribute to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24642" "T1027I" "NC_045512.2:g.3080C>T" "YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 1.51 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Mutation is predicted to lose the T cell epitope for people carrying DRB1*0301 and DRB1*0401, but not for example in those who are DRB1*0701 or DRB1*1501 who would be predicted to show an enhanced response. This is also observed in a study of 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25046" "P1162S" "NC_045512.2:g.3484C>T" "YP_009724390.1:p.Pro1162Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25249,25249,25249" "M1229I,M1229I,M1229I" "NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25350" "P1263L" "NC_045512.2:g.3788C>T" "YP_009724390.1:p.Pro1263Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant in the cytoplasmic tail, shown in vitro to increase Spike subunit fusion required for cell entry" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25855" "D155Y" "NC_045512.2:g.463G>T" "YP_009724391.1:p.Asp155Tyr" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "caveolin binding" "" "" "In silico, this mutation is the only one weakening ORF3a's binding affinity for caveolin-1 (essential for entry and endomembrane trafficking of SARS-CoV-2). This mutation is a widespread homoplasy in 20A and 20B lineages." "" "" "" "Gupta" "2021" "https://doi.org/10.1101/2021.03.26.437194" "doi:10.1101/2021.03.26.437194" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26029" "Q213K" "NC_045512.2:g.637C>A" "YP_009724391.1:p.Gln213Lys" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*01:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26029" "Q213K" "NC_045512.2:g.637C>A" "YP_009724391.1:p.Gln213Lys" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*01:01-restricted CD8+ ORF3a epitope, which is otherwise ""consistently dominant and of high magnitude""." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26256" "F4F" "NC_045512.2:g.12C>T" "YP_009724392.1:p.Phe4Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26268,26269,26270" "T9I,T9I,T9I" "NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T" "YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~300 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26268,26269,26270" "T9I,T9I,T9I" "NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T" "YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26296" "L18I" "NC_045512.2:g.52C>A" "YP_009724392.1:p.Leu18Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (47x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26299" "L19F" "NC_045512.2:g.55C>T" "YP_009724392.1:p.Leu19Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26312" "F23C" "NC_045512.2:g.68T>G" "YP_009724392.1:p.Phe23Cys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~8.8 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26314" "V24M" "NC_045512.2:g.70G>A" "YP_009724392.1:p.Val24Met" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26319" "V25V" "NC_045512.2:g.75A>G" "YP_009724392.1:p.Val25Val" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (45x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26333" "T30I" "NC_045512.2:g.89C>T" "YP_009724392.1:p.Thr30Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26353" "L37F" "NC_045512.2:g.109C>T" "YP_009724392.1:p.Leu37Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26395" "L51I" "NC_045512.2:g.151C>A" "YP_009724392.1:p.Leu51Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (47x overrepresentation vs expected count of ~24 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26416" "V58L" "NC_045512.2:g.172G>C" "YP_009724392.1:p.Val58Leu" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26428" "V62F" "NC_045512.2:g.184G>T" "YP_009724392.1:p.Val62Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (18x overrepresentation vs expected count of ~333 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26442" "N66K" "NC_045512.2:g.198T>G" "YP_009724392.1:p.Asn66Lys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~23 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26447" "S68F" "NC_045512.2:g.203C>T" "YP_009724392.1:p.Ser68Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26447" "S68C" "NC_045512.2:g.203C>G" "YP_009724392.1:p.Ser68Cys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (58x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26456" "P71R" "NC_045512.2:g.212C>G" "YP_009724392.1:p.Pro71Arg" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26467" "V75L" "NC_045512.2:g.223G>C" "YP_009724392.1:p.Val75Leu" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (3762.7x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526" "A2S" "NC_045512.2:g.4G>T" "YP_009724393.1:p.Ala2Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Emergent as 16% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing." "" "" "" "Avanzato" "2020" "https://doi.org/10.1016/j.cell.2020.10.049" "doi:10.1016/j.cell.2020.10.049" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526" "A2S" "NC_045512.2:g.4G>T" "YP_009724393.1:p.Ala2Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (38x overrepresentation vs expected count of ~334 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526,26527,26529" "D3H,D3H,D3H" "NC_045512.2:g.7G>C,NC_045512.2:g.7G>C,NC_045512.2:g.7G>C" "YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (227x overrepresentation vs expected count of ~14 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26528,26528,26528" "A2A,A2A,A2A" "NC_045512.2:g.6A>T,NC_045512.2:g.6A>G,NC_045512.2:g.6A>C" "YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (25x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26530" "D3G" "NC_045512.2:g.8A>G" "YP_009724393.1:p.Asp3Gly" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (31x overrepresentation vs expected count of ~53 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26542" "T7I" "NC_045512.2:g.20C>T" "YP_009724393.1:p.Thr7Ile" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26546" "I8I" "NC_045512.2:g.24T>C" "YP_009724393.1:p.Ile8Ile" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~80 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26573,26576,26577" "Q19E,Q19E,Q19E" "NC_045512.2:g.55C>G,NC_045512.2:g.55C>G,NC_045512.2:g.55C>G" "YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~8 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26620" "C33S" "NC_045512.2:g.98G>C" "YP_009724393.1:p.Cys33Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~32 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26645" "N41N" "NC_045512.2:g.123C>T" "YP_009724393.1:p.Asn41Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (19x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26681" "F53F" "NC_045512.2:g.159C>T" "YP_009724393.1:p.Phe53Phe" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (163x overrepresentation vs expected count of ~567 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26730" "V70L" "NC_045512.2:g.208G>C" "YP_009724393.1:p.Val70Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26748" "I76V" "NC_045512.2:g.226A>G" "YP_009724393.1:p.Ile76Val" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26748" "I76L" "NC_045512.2:g.226A>C" "YP_009724393.1:p.Ile76Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~9 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26749" "I76T" "NC_045512.2:g.227T>C" "YP_009724393.1:p.Ile76Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (19x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26767" "I82T" "NC_045512.2:g.245T>C" "YP_009724393.1:p.Ile82Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "homoplasy" "" "" "This mutation presents mainly within the B.1 (44.0%) and B.1.525 (38.1%) lineages. Currently, 99.7% of the B.1.525 lineage isolates carry the M:I82T mutation. While this mutation is scattered across multiple phylogenetic clades, most cases cluster in two recent clades, suggesting a likely selective advantage in certain haplotype backgrounds." "" "" "" "Shen" "2021" "https://doi.org/10.1080/22221751.2021.1922097" "doi:10.1080/22221751.2021.1922097" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26767" "I82T" "NC_045512.2:g.245T>C" "YP_009724393.1:p.Ile82Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (67x overrepresentation vs expected count of ~42 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26801,26801,26801" "L93L,L93L,L93L" "NC_045512.2:g.279C>G,NC_045512.2:g.279C>A,NC_045512.2:g.279C>T" "YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~628 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26855,26858" "F112F,F112F" "NC_045512.2:g.336C>T,NC_045512.2:g.336C>T" "YP_009724393.1:p.Phe112Phe,YP_009724393.1:p.Phe112Phe" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~463 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26861" "N113N" "NC_045512.2:g.339T>C" "YP_009724393.1:p.Asn113Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (57x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26873" "N117N" "NC_045512.2:g.351C>T" "YP_009724393.1:p.Asn117Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26882,26882" "L120L,L120L" "NC_045512.2:g.360C>A,NC_045512.2:g.360C>T" "YP_009724393.1:p.Leu120Leu,YP_009724393.1:p.Leu120Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26894,26894" "L124L,L124L" "NC_045512.2:g.372C>T,NC_045512.2:g.372C>G" "YP_009724393.1:p.Leu124Leu,YP_009724393.1:p.Leu124Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26895" "H125Y" "NC_045512.2:g.373C>T" "YP_009724393.1:p.His125Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (22x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26895" "H125Y" "NC_045512.2:g.373C>T" "YP_009724393.1:p.His125Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARA_CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26907,26909,26909" "L129L,L129L,L129L" "NC_045512.2:g.385C>T,NC_045512.2:g.387G>A,NC_045512.2:g.387G>T" "YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26927" "E135E" "NC_045512.2:g.405A>G" "YP_009724393.1:p.Glu135Glu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (232x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26951,26951,26951" "V143V,V143V,V143V" "NC_045512.2:g.429G>C,NC_045512.2:g.429G>A,NC_045512.2:g.429G>T" "YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~508 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26966" "H148H" "NC_045512.2:g.444T>C" "YP_009724393.1:p.His148His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26972" "R150R" "NC_045512.2:g.450T>C" "YP_009724393.1:p.Arg150Arg" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~89 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26985" "H155N" "NC_045512.2:g.463C>A" "YP_009724393.1:p.His155Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26987" "H155H" "NC_045512.2:g.465T>C" "YP_009724393.1:p.His155His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27021" "E167Q" "NC_045512.2:g.499G>C" "YP_009724393.1:p.Glu167Gln" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27035,27038" "T172T,T172T" "NC_045512.2:g.516A>G,NC_045512.2:g.516A>G" "YP_009724393.1:p.Thr172Thr,YP_009724393.1:p.Thr172Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27059" "Y179Y" "NC_045512.2:g.537C>T" "YP_009724393.1:p.Tyr179Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27112" "S197T" "NC_045512.2:g.590G>C" "YP_009724393.1:p.Ser197Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (18x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27134" "Y204Y" "NC_045512.2:g.612T>C" "YP_009724393.1:p.Tyr204Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27143" "N207N" "NC_045512.2:g.621C>T" "YP_009724393.1:p.Asn207Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27147" "D209H" "NC_045512.2:g.625G>C" "YP_009724393.1:p.Asp209His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (81x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27367" "Q56X" "NC_045512.2:g.166C>T" "YP_009724394.1:p.Gln56Xaa" "" "open reading frame 6 gene (SARS-CoV-2)" "orf6 gene (SARS-CoV-2)" "open reading frame 6 protein (SARS-CoV-2)" "Orf6 protein (SARS-CoV-2)" "IFN activity" "" "" "The residues listed are determinants of the potent IFN-antagonistic activity of SARS-CoV-2 ORF6 (via blocking mRNA nuclear export)" "" "" "" "Kimura" "2020" "https://doi.org/10.2139/ssrn.3690468" "doi:10.2139/ssrn.3690468" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28144" "L84S" "NC_045512.2:g.251T>C" "YP_009724396.1:p.Leu84Ser" "" "open reading frame 8 gene (SARS-CoV-2)" "orf8 gene (SARS-CoV-2)" "open reading frame 8 protein (SARS-CoV-2)" "Orf8 protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28307,28309,28310,28311" "P13L,P13L,P13L,P13L" "NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T" "YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28307,28309,28310,28311" "P13L,P13L,P13L,P13L" "NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T" "YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13)." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28310" "P13S" "NC_045512.2:g.37C>T" "YP_009724397.2:p.Pro13Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13)." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28310" "P13S" "NC_045512.2:g.37C>T" "YP_009724397.2:p.Pro13Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*27:05." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28769" "T166A" "NC_045512.2:g.496A>G" "YP_009724397.2:p.Thr166Ala" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "Confers a significant PIWAS value decrease (reduced antigenicity)" "" "" "" "Haynes" "2020" "https://doi.org/10.1101/2020.11.23.20235002" "doi:10.1101/2020.11.23.20235002" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28853" "S194T" "NC_045512.2:g.580T>A" "YP_009724397.2:p.Ser194Thr" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28854" "S194L" "NC_045512.2:g.581C>T" "YP_009724397.2:p.Ser194Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "Mutation with a population frequency of 30% in a Mexican dataset, primarily of lineage 20B, but also present in a substantial number of 20A lineage sequences, suggesting convergent evolution." "" "" "" "Barona-Gomez" "2021" "https://doi.org/10.1101/2021.05.18.21256128" "doi:10.1101/2021.05.18.21256128" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28854" "S194L" "NC_045512.2:g.581C>T" "YP_009724397.2:p.Ser194Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In March 2021 this variant had an allele frequency of 47.62 and 7.25% in deceased patients, compared to 35.16 and 3.20% of the same variant in recovered patients, from the Gujarat and global datasets." "" "" "" "Joshi" "2021" "https://doi.org/10.3389/fgene.2021.586569" "doi:10.3389/fgene.2021.586569" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28869" "P199L" "NC_045512.2:g.596C>T" "YP_009724397.2:p.Pro199Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28879" "S202R" "NC_045512.2:g.606T>G" "YP_009724397.2:p.Ser202Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows major increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881" "R203M" "NC_045512.2:g.608G>T" "YP_009724397.2:p.Arg203Met" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows most increase in RNA content of any N mutation tested, suggesting that this mutation improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28977" "S235F" "NC_045512.2:g.704C>T" "YP_009724397.2:p.Ser235Phe" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "Substantially increases epitope and antigen scores in 2 of 579 individuals (should increase immune response). In the B1.1.7 lineage this is largely counteracted by the D3L mutation, which decreases PIWAS signal significantly in 1.5% of COVID patients, for a net neutral effect at the population level." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29239,29239" "M322I,M322I" "NC_045512.2:g.966G>A,NC_045512.2:g.966G>T" "YP_009724397.2:p.Met322Ile,YP_009724397.2:p.Met322Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "Agerer" "2021" "https://doi.org/10.1126/sciimmunol.abg6461" "doi:10.1126/sciimmunol.abg6461" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29247" "T325I" "NC_045512.2:g.974C>T" "YP_009724397.2:p.Thr325Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes partial loss of T cell line responsiveness and CTL killing ability by B*40:01-restricted CD8+ N epitope MEVTPSGTWL 322-331." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29247" "T325I" "NC_045512.2:g.974C>T" "YP_009724397.2:p.Thr325Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29266,29266" "L331F,L331F" "NC_045512.2:g.993G>T,NC_045512.2:g.993G>C" "YP_009724397.2:p.Leu331Phe,YP_009724397.2:p.Leu331Phe" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "Agerer" "2021" "https://doi.org/10.1126/sciimmunol.abg6461" "doi:10.1126/sciimmunol.abg6461" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29409" "T379I" "NC_045512.2:g.1136C>T" "YP_009724397.2:p.Thr379Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "335" "R24C" "NC_045512.2:g.70C>T" "YP_009724389.1:p.Arg24Cys" "YP_009724389.1:Arg24Cys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (25x overrepresentation vs expected count of 514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "347" "V28I" "NC_045512.2:g.82G>A" "YP_009724389.1:p.Val28Ile" "YP_009724389.1:Val28Ile" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (30x overrepresentation vs expected count of 143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "383" "S40P" "NC_045512.2:g.118T>C" "YP_009724389.1:p.Ser40Pro" "YP_009724389.1:Ser40Pro" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~58 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "396" "Q44L" "NC_045512.2:g.131A>T" "YP_009724389.1:p.Gln44Leu" "YP_009724389.1:Gln44Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~19 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "443" "V60I" "NC_045512.2:g.178G>A" "YP_009724389.1:p.Val60Ile" "YP_009724389.1:Val60Ile" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "489" "D75G" "NC_045512.2:g.224A>G" "YP_009724389.1:p.Asp75Gly" "YP_009724389.1:Asp75Gly" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "490,490" "D75E,D75E" "NC_045512.2:g.225T>G,NC_045512.2:g.225T>A" "YP_009724389.1:p.Asp75Glu,YP_009724389.1:p.Asp75Glu" "YP_009724389.1:Asp75Glu,YP_009724389.1:Asp75Glu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~20 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Emergent as 22% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing." "" "" "" "Avanzato" "2020" "https://doi.org/10.1016/j.cell.2020.10.049" "doi:10.1016/j.cell.2020.10.049" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-517) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-523) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 500-523) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,509,518" "M85V,M85V,M85V" "NC_045512.2:g.253A>G,NC_045512.2:g.253A>G,NC_045512.2:g.253A>G" "YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val" "YP_009724389.1:Met85Val,YP_009724389.1:Met85Val,YP_009724389.1:Met85Val" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "508" "H81Q" "NC_045512.2:g.243T>A" "YP_009724389.1:p.His81Gln" "YP_009724389.1:His81Gln" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (30x overrepresentation vs expected count of ~20 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "510" "M85K" "NC_045512.2:g.254T>A" "YP_009724389.1:p.Met85Lys" "YP_009724389.1:Met85Lys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~12 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "561" "R99H" "NC_045512.2:g.296G>A" "YP_009724389.1:p.Arg99His" "YP_009724389.1:Arg99His" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "563" "S100C" "NC_045512.2:g.298A>T" "YP_009724389.1:p.Ser100Cys" "YP_009724389.1:Ser100Cys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (33x overrepresentation vs expected count of ~19 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "593" "H110Y" "NC_045512.2:g.328C>T" "YP_009724389.1:p.His110Tyr" "YP_009724389.1:His110Tyr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (22x overrepresentation vs expected count of ~514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "593" "H110D" "NC_045512.2:g.328C>G" "YP_009724389.1:p.His110Asp" "YP_009724389.1:His110Asp" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~11 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "606" "I114T" "NC_045512.2:g.341T>C" "YP_009724389.1:p.Ile114Thr" "YP_009724389.1:Ile114Thr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (155x overrepresentation vs expected count of ~58 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "657" "A131V" "NC_045512.2:g.392C>T" "YP_009724389.1:p.Ala131Val" "YP_009724389.1:Ala131Val" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "677" "A138T" "NC_045512.2:g.412G>A" "YP_009724389.1:p.Ala138Thr" "YP_009724389.1:Ala138Thr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "761" "S166G" "NC_045512.2:g.496A>G" "YP_009724389.1:p.Ser166Gly" "YP_009724389.1:Ser166Gly" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (132x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "798" "N178S" "NC_045512.2:g.533A>G" "YP_009724389.1:p.Asn178Ser" "YP_009724389.1:Asn178Ser" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" From 9ed5809990d7f9704055edbe48258b65d7a0ec47 Mon Sep 17 00:00:00 2001 From: miseminger Date: Sun, 27 Oct 2024 21:25:28 -0700 Subject: [PATCH 079/161] catch MPOX genes and proteins --- bin/convert_pokay_to_virusmvp.py | 44 ++++++++++++++++++++++++-------- 1 file changed, 34 insertions(+), 10 deletions(-) diff --git a/bin/convert_pokay_to_virusmvp.py b/bin/convert_pokay_to_virusmvp.py index 1f37d71f..6324a1e0 100755 --- a/bin/convert_pokay_to_virusmvp.py +++ b/bin/convert_pokay_to_virusmvp.py @@ -292,18 +292,42 @@ def write_tsv(dframe): dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene orientation"] = gene_orientation dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "strand orientation"] = strand_orientation - # If a CDS record matches pokay_id, get 'protein_name' and 'protein_symbol' - if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="CDS" and ("gene" in GENE_PROTEIN_POSITIONS_DICT[entry].keys()) and GENE_PROTEIN_POSITIONS_DICT[entry]["gene"]==pokay_id: - # extract protein names and symbols (ontology) from JSON entry - protein_name = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_name"]["label"] - protein_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_symbol"]["label"] - # add protein names and symbols to dataframe - dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "protein name"] = protein_name - dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "protein symbol"] = protein_symbol + # If a CDS record matches pokay_id in 'gene' or 'protein_alias', get 'protein_name' and 'protein_symbol' + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="CDS" and ("gene" in GENE_PROTEIN_POSITIONS_DICT[entry].keys()): + if (GENE_PROTEIN_POSITIONS_DICT[entry]["gene"]==pokay_id): + # extract protein names and symbols (ontology) from JSON entry + protein_name = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_name"]["label"] + protein_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_symbol"]["label"] + # add protein names and symbols to dataframe + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "protein name"] = protein_name + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "protein symbol"] = protein_symbol + elif (pokay_id in GENE_PROTEIN_POSITIONS_DICT[entry]["protein_alias"]): + gene = GENE_PROTEIN_POSITIONS_DICT[entry]["gene"] + # extract protein names and symbols (ontology) from JSON entry + protein_name = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_name"]["label"] + protein_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["protein_symbol"]["label"] + # add protein names and symbols to dataframe + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "protein name"] = protein_name + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "protein symbol"] = protein_symbol + # get 'gene_name' and 'gene_symbol' + for entry in GENE_PROTEIN_POSITIONS_DICT.keys(): + if GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="gene" and ("gene" in GENE_PROTEIN_POSITIONS_DICT[entry].keys()) and GENE_PROTEIN_POSITIONS_DICT[entry]["gene"]==gene: + # extract protein names and symbols (ontology) from JSON entry + gene_name = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_name"]["label"] + gene_symbol = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_symbol"]["label"] + gene_orientation = GENE_PROTEIN_POSITIONS_DICT[entry]["gene_orientation"]["label"] + strand_orientation = GENE_PROTEIN_POSITIONS_DICT[entry]["strand_orientation"]["label"] + # add gene names and symbols to dataframe + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene name"] = gene_name + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene symbol"] = gene_symbol + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene"] = GENE_PROTEIN_POSITIONS_DICT[entry]["gene"] + if args.accession=='NC_063383.1': # add gene orientation and strand orientation for MPOX + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "gene orientation"] = gene_orientation + dataFrame.loc[dataFrame["pokay_id"]==pokay_id, "strand orientation"] = strand_orientation + # If a mature peptide record matches pokay_id in the 'protein_alias' list, get name of parent, and from there get names and symbols - if (GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="mature_protein_region_of_CDS" or \ - (GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="CDS" and args.accession=='NC_063383.1')) \ + if (GENE_PROTEIN_POSITIONS_DICT[entry]["type"]=="mature_protein_region_of_CDS") \ and (pokay_id in GENE_PROTEIN_POSITIONS_DICT[entry]["protein_alias"]): # extract pokay_id, mat_pep, and parent id from JSON entry mat_pep = entry From 2803cc7bae77d0677b36a29aaec0f7c85127f5e8 Mon Sep 17 00:00:00 2001 From: miseminger Date: Sun, 27 Oct 2024 23:04:01 -0700 Subject: [PATCH 080/161] catch MPOX URLs --- bin/convert_pokay_to_virusmvp.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/bin/convert_pokay_to_virusmvp.py b/bin/convert_pokay_to_virusmvp.py index 6324a1e0..86dd5af2 100755 --- a/bin/convert_pokay_to_virusmvp.py +++ b/bin/convert_pokay_to_virusmvp.py @@ -88,7 +88,7 @@ def extract_source_citation(dframe): dframe['publication year'] = dframe['citation'].str.extract('.*\((.*)\).*') dframe['author'] = dframe['citation'].str.extract('^(.*?)et al') #.str.strip() dframe['peer review status'] = dframe['URL'].astype(str).str.extract('(?<=\[)(.*)') - dframe['URL'] = dframe['URL'].astype(str).str.extract('^(.*?)\[') #.str.strip() + dframe['URL'] = dframe['URL'].astype(str).str.split(expand=True)[0] dframe['DOI'] = dframe['URL'].astype(str).str.extract('(?<=doi.org/)(.*)') #.str.strip() return dframe From 86f9d3ca3c486894d54a0f907a24d7af466f7eab Mon Sep 17 00:00:00 2001 From: miseminger Date: Sun, 27 Oct 2024 23:04:31 -0700 Subject: [PATCH 081/161] upload MPOX functional annotation file --- .../NC_063383.1/Pokay_functionalAnnotation_MPOX_v1.0.tsv | 7 +++++++ 1 file changed, 7 insertions(+) create mode 100644 assets/virus_functionalAnnotation/NC_063383.1/Pokay_functionalAnnotation_MPOX_v1.0.tsv diff --git a/assets/virus_functionalAnnotation/NC_063383.1/Pokay_functionalAnnotation_MPOX_v1.0.tsv b/assets/virus_functionalAnnotation/NC_063383.1/Pokay_functionalAnnotation_MPOX_v1.0.tsv new file mode 100644 index 00000000..a03dbcdb --- /dev/null +++ b/assets/virus_functionalAnnotation/NC_063383.1/Pokay_functionalAnnotation_MPOX_v1.0.tsv @@ -0,0 +1,7 @@ +organism reference accession reference database name nucleotide position original mutation description nucleotide mutation amino acid mutation amino acid mutation alias gene name gene symbol gene orientation strand orientation protein name protein symbol measured variant functional effect inferred variant functional effect viral life cycle functional effect variant functional effect description CVX code DrugBank Accession Number Antibody Registry ID author publication year URL DOI PMID peer review status curator mutation functional annotation resource +Monkeypox virus NC_063383.1 RefSeq T220A orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in two site samples (0.44 and 0.49 frequency, culture contaminated and culture negative respectively) from an HIV-positive patient treated with Tecovirimat. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 37338408 Paul Gordon Pokay +Monkeypox virus NC_063383.1 RefSeq T220I orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in two site samples (0.44 and 0.49 frequency, culture contaminated and culture negative respectively) from an HIV-positive patient treated with Tecovirimat. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 37338408 Paul Gordon Pokay +Monkeypox virus NC_063383.1 RefSeq T245I orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.12 frequency, culture positive with EC50 0.3820uM) from an HIV-positive patient treated with Tecovirimat, may be dragged along by D294V (known from literature) from same sample with 0.91 frequency. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 37338408 Paul Gordon Pokay +Monkeypox virus NC_063383.1 RefSeq D294V orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.91 frequency, culture positive with EC50 0.3820uM) from an HIV-positive patient treated with Tecovirimat. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 37338408 Paul Gordon Pokay +Monkeypox virus NC_063383.1 RefSeq A265D orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.5 frequency, culture contaminated) from an HIV-positive patient treated with Tecovirimat. Novel T220A also found at similar frequency (0.44) in the same sample, as well as A295E which is known from the literature (0.51 frequency). Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 37338408 Paul Gordon Pokay +Monkeypox virus NC_063383.1 RefSeq T289A orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.41 frequency, culture data pending) from an HIV-positive patient treated with Tecovirimat. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 37338408 Paul Gordon Pokay From ef4c60cfdfb46ce2e77de749aa567fd4597936a6 Mon Sep 17 00:00:00 2001 From: miseminger Date: Sun, 27 Oct 2024 23:13:50 -0700 Subject: [PATCH 082/161] add 'pmid:' prefix --- .../Pokay_functionalAnnotation_MPOX_v1.0.tsv | 12 ++++++------ 1 file changed, 6 insertions(+), 6 deletions(-) diff --git a/assets/virus_functionalAnnotation/NC_063383.1/Pokay_functionalAnnotation_MPOX_v1.0.tsv b/assets/virus_functionalAnnotation/NC_063383.1/Pokay_functionalAnnotation_MPOX_v1.0.tsv index a03dbcdb..b4188e01 100644 --- a/assets/virus_functionalAnnotation/NC_063383.1/Pokay_functionalAnnotation_MPOX_v1.0.tsv +++ b/assets/virus_functionalAnnotation/NC_063383.1/Pokay_functionalAnnotation_MPOX_v1.0.tsv @@ -1,7 +1,7 @@ organism reference accession reference database name nucleotide position original mutation description nucleotide mutation amino acid mutation amino acid mutation alias gene name gene symbol gene orientation strand orientation protein name protein symbol measured variant functional effect inferred variant functional effect viral life cycle functional effect variant functional effect description CVX code DrugBank Accession Number Antibody Registry ID author publication year URL DOI PMID peer review status curator mutation functional annotation resource -Monkeypox virus NC_063383.1 RefSeq T220A orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in two site samples (0.44 and 0.49 frequency, culture contaminated and culture negative respectively) from an HIV-positive patient treated with Tecovirimat. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 37338408 Paul Gordon Pokay -Monkeypox virus NC_063383.1 RefSeq T220I orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in two site samples (0.44 and 0.49 frequency, culture contaminated and culture negative respectively) from an HIV-positive patient treated with Tecovirimat. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 37338408 Paul Gordon Pokay -Monkeypox virus NC_063383.1 RefSeq T245I orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.12 frequency, culture positive with EC50 0.3820uM) from an HIV-positive patient treated with Tecovirimat, may be dragged along by D294V (known from literature) from same sample with 0.91 frequency. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 37338408 Paul Gordon Pokay -Monkeypox virus NC_063383.1 RefSeq D294V orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.91 frequency, culture positive with EC50 0.3820uM) from an HIV-positive patient treated with Tecovirimat. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 37338408 Paul Gordon Pokay -Monkeypox virus NC_063383.1 RefSeq A265D orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.5 frequency, culture contaminated) from an HIV-positive patient treated with Tecovirimat. Novel T220A also found at similar frequency (0.44) in the same sample, as well as A295E which is known from the literature (0.51 frequency). Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 37338408 Paul Gordon Pokay -Monkeypox virus NC_063383.1 RefSeq T289A orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.41 frequency, culture data pending) from an HIV-positive patient treated with Tecovirimat. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 37338408 Paul Gordon Pokay +Monkeypox virus NC_063383.1 RefSeq T220A orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in two site samples (0.44 and 0.49 frequency, culture contaminated and culture negative respectively) from an HIV-positive patient treated with Tecovirimat. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 pmid:37338408 Paul Gordon Pokay +Monkeypox virus NC_063383.1 RefSeq T220I orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in two site samples (0.44 and 0.49 frequency, culture contaminated and culture negative respectively) from an HIV-positive patient treated with Tecovirimat. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 pmid:37338408 Paul Gordon Pokay +Monkeypox virus NC_063383.1 RefSeq T245I orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.12 frequency, culture positive with EC50 0.3820uM) from an HIV-positive patient treated with Tecovirimat, may be dragged along by D294V (known from literature) from same sample with 0.91 frequency. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 pmid:37338408 Paul Gordon Pokay +Monkeypox virus NC_063383.1 RefSeq D294V orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.91 frequency, culture positive with EC50 0.3820uM) from an HIV-positive patient treated with Tecovirimat. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 pmid:37338408 Paul Gordon Pokay +Monkeypox virus NC_063383.1 RefSeq A265D orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.5 frequency, culture contaminated) from an HIV-positive patient treated with Tecovirimat. Novel T220A also found at similar frequency (0.44) in the same sample, as well as A295E which is known from the literature (0.51 frequency). Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 pmid:37338408 Paul Gordon Pokay +Monkeypox virus NC_063383.1 RefSeq T289A orthopoxvirus gene 057 (MPOX) opg057 gene (MPOX) forward gene orientation sense strand orientation Palmytilated EEV membrane protein (MPOX) Opg057 protein (MPOX) drug resistence May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.41 frequency, culture data pending) from an HIV-positive patient treated with Tecovirimat. Garrigues 2023 https://doi.org/10.1128/aac.00568-23 doi:10.1128/aac.00568-23 pmid:37338408 Paul Gordon Pokay From aef4ab38c5cbb083643119467b0ea988cfd423cb Mon Sep 17 00:00:00 2001 From: miseminger Date: Sun, 27 Oct 2024 23:13:59 -0700 Subject: [PATCH 083/161] add 'pmid:' prefix --- bin/addpmids2functionalannotation.py | 3 ++- 1 file changed, 2 insertions(+), 1 deletion(-) diff --git a/bin/addpmids2functionalannotation.py b/bin/addpmids2functionalannotation.py index 70cd216b..c1f11271 100755 --- a/bin/addpmids2functionalannotation.py +++ b/bin/addpmids2functionalannotation.py @@ -39,11 +39,12 @@ def parse_args(): pmids_df = pmids_df.drop_duplicates(subset='DOI', keep='first') pmids_df = pmids_df[['PMID', 'DOI']] pmids_df['DOI'] = "doi:" + pmids_df['DOI'] + pmids_df['PMID'] = "pmid:" + pmids_df['PMID'].astype(str) #merge them functional_annotation_df = functional_annotation_df.drop(columns='PMID') functional_annotation_df = pd.merge(functional_annotation_df, pmids_df, on='DOI', how='left') - functional_annotation_df["PMID"] = functional_annotation_df["PMID"].astype('Int64') + #functional_annotation_df["PMID"] = functional_annotation_df["PMID"].astype('Int64') # rearrange columns functional_annotation_df = functional_annotation_df[functional_annotation_columns] From 866bc56440e366a3c821f2f7d2cd567fef98b6bb Mon Sep 17 00:00:00 2001 From: Madeline Iseminger <32916719+miseminger@users.noreply.github.com> Date: Mon, 28 Oct 2024 10:53:34 -0700 Subject: [PATCH 084/161] Delete assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.1.tsv --- .../NC_063383.1/pokay_annotations_v_0.1.tsv | 7 ------- 1 file changed, 7 deletions(-) delete mode 100644 assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.1.tsv diff --git a/assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.1.tsv b/assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.1.tsv deleted file mode 100644 index a1c962e9..00000000 --- a/assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.1.tsv +++ /dev/null @@ -1,7 +0,0 @@ -"mutation" "gene" "function_category" "comb_mutation" "heterozygosity" "citation" "source" "function_description" -"T220A" "VP37" "drug resistence" "" "" " Garrigues et al. (2023) " " https://doi.org/10.1128/aac.00568-23" " May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in two site samples (0.44 and 0.49 frequency, culture contaminated and culture negative respectively) from an HIV-positive patient treated with Tecovirimat." -"T220I" "VP37" "drug resistence" "" "" " Garrigues et al. (2023) " " https://doi.org/10.1128/aac.00568-23" " May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in two site samples (0.44 and 0.49 frequency, culture contaminated and culture negative respectively) from an HIV-positive patient treated with Tecovirimat." -"T245I" "VP37" "drug resistence" "" "" " Garrigues et al. (2023) " " https://doi.org/10.1128/aac.00568-23" " May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.12 frequency, culture positive with EC50 0.3820uM) from an HIV-positive patient treated with Tecovirimat, may be dragged along by D294V (known from literature) from same sample with 0.91 frequency." -"D294V" "VP37" "drug resistence" "" "" " Garrigues et al. (2023) " " https://doi.org/10.1128/aac.00568-23" " May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.91 frequency, culture positive with EC50 0.3820uM) from an HIV-positive patient treated with Tecovirimat." -"A265D" "VP37" "drug resistence" "" "" " Garrigues et al. (2023) " " https://doi.org/10.1128/aac.00568-23" " May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.5 frequency, culture contaminated) from an HIV-positive patient treated with Tecovirimat. Novel T220A also found at similar frequency (0.44) in the same sample, as well as A295E which is known from the literature (0.51 frequency)." -"T289A" "VP37" "drug resistence" "" "" " Garrigues et al. (2023) " " https://doi.org/10.1128/aac.00568-23" " May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.41 frequency, culture data pending) from an HIV-positive patient treated with Tecovirimat." From d7eecc323a74684418e8d07e0fedc2fca2219f9e Mon Sep 17 00:00:00 2001 From: Madeline Iseminger <32916719+miseminger@users.noreply.github.com> Date: Mon, 28 Oct 2024 10:53:50 -0700 Subject: [PATCH 085/161] Delete assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.2.tsv --- .../NC_063383.1/pokay_annotations_v_0.2.tsv | 7 ------- 1 file changed, 7 deletions(-) delete mode 100644 assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.2.tsv diff --git a/assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.2.tsv b/assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.2.tsv deleted file mode 100644 index 076dd420..00000000 --- a/assets/virus_functionalAnnotation/NC_063383.1/pokay_annotations_v_0.2.tsv +++ /dev/null @@ -1,7 +0,0 @@ -"organism" "reference accession" "reference database name" "nucleotide position" "original mutation description" "nucleotide mutation" "amino acid mutation" "amino acid mutation alias" "gene name" "gene symbol" "gene orientation" "strand orientation" "protein name" "protein symbol" "measured variant functional effect" "inferred variant functional effect" "viral life cycle functional effect" "measured variant functional effect description" "CVX code" "DrugBank Accession Number" "Antibody Registry ID" "author" "publication year" "URL" "DOI" "PMID" "peer review status" "curator" "mutation functional annotation resource" -"Monkeypox virus" "NC_063383.1" "RefSeq" "" "T220A" "" "" "" "" "" "" "" "" "" "drug resistence" "" "" "May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in two site samples (0.44 and 0.49 frequency, culture contaminated and culture negative respectively) from an HIV-positive patient treated with Tecovirimat." "" "" "" "Garrigues" "2023" "" "" "" "unknown" "Paul Gordon" "Pokay" -"Monkeypox virus" "NC_063383.1" "RefSeq" "" "T220I" "" "" "" "" "" "" "" "" "" "drug resistence" "" "" "May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in two site samples (0.44 and 0.49 frequency, culture contaminated and culture negative respectively) from an HIV-positive patient treated with Tecovirimat." "" "" "" "Garrigues" "2023" "" "" "" "unknown" "Paul Gordon" "Pokay" -"Monkeypox virus" "NC_063383.1" "RefSeq" "" "T245I" "" "" "" "" "" "" "" "" "" "drug resistence" "" "" "May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.12 frequency, culture positive with EC50 0.3820uM) from an HIV-positive patient treated with Tecovirimat, may be dragged along by D294V (known from literature) from same sample with 0.91 frequency." "" "" "" "Garrigues" "2023" "" "" "" "unknown" "Paul Gordon" "Pokay" -"Monkeypox virus" "NC_063383.1" "RefSeq" "" "D294V" "" "" "" "" "" "" "" "" "" "drug resistence" "" "" "May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.91 frequency, culture positive with EC50 0.3820uM) from an HIV-positive patient treated with Tecovirimat." "" "" "" "Garrigues" "2023" "" "" "" "unknown" "Paul Gordon" "Pokay" -"Monkeypox virus" "NC_063383.1" "RefSeq" "" "A265D" "" "" "" "" "" "" "" "" "" "drug resistence" "" "" "May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.5 frequency, culture contaminated) from an HIV-positive patient treated with Tecovirimat. Novel T220A also found at similar frequency (0.44) in the same sample, as well as A295E which is known from the literature (0.51 frequency)." "" "" "" "Garrigues" "2023" "" "" "" "unknown" "Paul Gordon" "Pokay" -"Monkeypox virus" "NC_063383.1" "RefSeq" "" "T289A" "" "" "" "" "" "" "" "" "" "drug resistence" "" "" "May represent novel Tecovirimat-resistence mutation as likely at the interaction interface for the drug and observed in a single site sample (0.41 frequency, culture data pending) from an HIV-positive patient treated with Tecovirimat." "" "" "" "Garrigues" "2023" "" "" "" "unknown" "Paul Gordon" "Pokay" From cfe4318b26acea6b702c24e2572698827b6bc391 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 28 Oct 2024 22:59:42 -0700 Subject: [PATCH 086/161] fixed typos --- bin/gvf2indexandlog.py | 2 +- bin/splitmutationnames_gvf.py | 6 +++--- 2 files changed, 4 insertions(+), 4 deletions(-) diff --git a/bin/gvf2indexandlog.py b/bin/gvf2indexandlog.py index d96146d9..24f6313f 100755 --- a/bin/gvf2indexandlog.py +++ b/bin/gvf2indexandlog.py @@ -63,7 +63,7 @@ def parse_args(): index['gene_symbol'] = gvf['gene_symbol'] index['protein_name'] = gvf['protein_name'] index['protein_symbol'] = gvf['protein_symbol'] - index['Pokay_annotation'] = gvf["function_description"].notna() + index['Pokay_annotation'] = gvf["variant_functional_effect_description"].notna() index['lineages'] = gvf['viral_lineage'] # tidying index = index.drop_duplicates() diff --git a/bin/splitmutationnames_gvf.py b/bin/splitmutationnames_gvf.py index 7f14f0fd..4df670c1 100755 --- a/bin/splitmutationnames_gvf.py +++ b/bin/splitmutationnames_gvf.py @@ -54,11 +54,11 @@ def parse_args(): # if names_to_split tsv is given, use it to split up the multi-amino acid names if args.names_to_split != None: # split names in "Names" attribute into separate rows - gvf = split_names(args.names_to_split, gvf, col_to_split='Name') + gvf = split_names(args.names_to_split, gvf, col_to_split='original_mutation_description') - # rename IDs: rows with the same entry in 'Name' + # rename IDs: rows with the same entry in 'original_mutation_description' # get the same ID - gvf['ID'] = 'ID_' + gvf.groupby('Name', sort=False).ngroup().astype(str) + gvf['ID'] = 'ID_' + gvf.groupby('original_mutation_description', sort=False).ngroup().astype(str) # merge attributes back into a single column gvf = rejoin_attributes(gvf, empty_attributes) From 41a685e37d498af6c7e16c14daa7939c8a228c5c Mon Sep 17 00:00:00 2001 From: miseminger Date: Fri, 8 Nov 2024 12:41:16 -0800 Subject: [PATCH 087/161] solve duplicated rows bug --- bin/splitmutationnames_functionalannotation.py | 14 ++++++++++---- 1 file changed, 10 insertions(+), 4 deletions(-) diff --git a/bin/splitmutationnames_functionalannotation.py b/bin/splitmutationnames_functionalannotation.py index 74688633..0bf9290e 100755 --- a/bin/splitmutationnames_functionalannotation.py +++ b/bin/splitmutationnames_functionalannotation.py @@ -46,7 +46,8 @@ def parse_args(): # read in functional annotations file df = pd.read_csv(args.functional_annotations, sep='\t', header=0) - + df = df.drop_duplicates() + dataFrame_cols = df.columns.tolist() + ['comb_mutation'] # remove any leading/trailing spaces @@ -64,11 +65,12 @@ def parse_args(): # convert not-null values to lists df.loc[df[column].notna(), column] = df[column].astype(str).str.split(',') #convert null values to empty lists - df.loc[df[column].isnull(),[column]] = df.loc[df[column].isnull(),column].apply(lambda x: []) + df[column] = df[column].fillna("").apply(list) + #df.loc[df[column].isnull(),[column]] = df.loc[df[column].isnull(),column].apply(lambda x: []) # make temporary column for lengths of lists len_count = column + ' length' df.loc[df[column].notna(), len_count] = df[column].str.len() - + print("made it") # make sure all columns have the same number of elements; if they don't, throw an error if not (df['original mutation description length'].equals(df['nucleotide position length'])): print("Original mutation description and nucleotide position columns are of unequal length") @@ -90,7 +92,7 @@ def parse_args(): padded_list = [a + b for a,b in zip(A_list, nas_to_add_list)] # column to explode padded with NaNs # add padded column to df df['amino acid mutation alias'] = padded_list - + # explode list columns df = unnest_multi(df, to_unnest, reset_index=True) @@ -138,8 +140,12 @@ def parse_args(): df['PMID'] = df['PMID'].str.replace('.0', '', regex=False) df['publication year'] = df['publication year'].str.replace('.0', '', regex=False) + # drop duplicate rows + df = df.drop_duplicates() + # save modified file filepath = args.out_functions print("Saved as: ", filepath) print("") df.to_csv(filepath, sep='\t', index=False, header=True) + From 74d268e0cc4f957a79a6fde98486b3058ed9c13c Mon Sep 17 00:00:00 2001 From: miseminger Date: Fri, 8 Nov 2024 12:51:45 -0800 Subject: [PATCH 088/161] remove troubleshooting print statement --- bin/splitmutationnames_functionalannotation.py | 3 +-- 1 file changed, 1 insertion(+), 2 deletions(-) diff --git a/bin/splitmutationnames_functionalannotation.py b/bin/splitmutationnames_functionalannotation.py index 0bf9290e..42265e0e 100755 --- a/bin/splitmutationnames_functionalannotation.py +++ b/bin/splitmutationnames_functionalannotation.py @@ -70,7 +70,7 @@ def parse_args(): # make temporary column for lengths of lists len_count = column + ' length' df.loc[df[column].notna(), len_count] = df[column].str.len() - print("made it") + # make sure all columns have the same number of elements; if they don't, throw an error if not (df['original mutation description length'].equals(df['nucleotide position length'])): print("Original mutation description and nucleotide position columns are of unequal length") @@ -146,6 +146,5 @@ def parse_args(): # save modified file filepath = args.out_functions print("Saved as: ", filepath) - print("") df.to_csv(filepath, sep='\t', index=False, header=True) From 54741fc70ca378d3ac7345385b8c981bbc4233ff Mon Sep 17 00:00:00 2001 From: miseminger Date: Fri, 8 Nov 2024 14:48:27 -0800 Subject: [PATCH 089/161] remove duplicate rows --- bin/convert_pokay_to_virusmvp.py | 8 ++++++-- 1 file changed, 6 insertions(+), 2 deletions(-) diff --git a/bin/convert_pokay_to_virusmvp.py b/bin/convert_pokay_to_virusmvp.py index 1f37d71f..144ce6de 100755 --- a/bin/convert_pokay_to_virusmvp.py +++ b/bin/convert_pokay_to_virusmvp.py @@ -353,9 +353,10 @@ def write_tsv(dframe): # remove doubled columns from dataFrame index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias'] dataFrame = dataFrame.drop(columns=index_cols_to_use) + # drop duplicate rows from mutation index + mutation_index = mutation_index.drop_duplicates(subset=index_cols_to_use) + # merge merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'gene'], how='left') #, 'mat_pep' - #dups = mutation_index[mutation_index.duplicated(subset=['nucleotide position', 'original mutation description'], keep=False)] - #dups = dups.sort_values(by='nucleotide position') #dups.to_csv('madeline_testing/dups.tsv', sep='\t', index=False) # keep only specified columns, discarding 'pokay_id' here @@ -396,6 +397,9 @@ def write_tsv(dframe): # reorder columns and drop 'index1' merged_dataFrame = merged_dataFrame[dataFrame_cols] + # drop duplicates + merged_dataFrame = merged_dataFrame.drop_duplicates() + # sort by nucleotide position and reindex merged_dataFrame = merged_dataFrame.sort_values(by='nucleotide position') merged_dataFrame = merged_dataFrame.reindex() From 194133ef21703e4a38c34166b500422f457f6f03 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 12 Nov 2024 16:34:50 -0800 Subject: [PATCH 090/161] solve duplication issue --- bin/addfunctions2gvf.py | 1 + 1 file changed, 1 insertion(+) diff --git a/bin/addfunctions2gvf.py b/bin/addfunctions2gvf.py index d7699bb9..d939f747 100755 --- a/bin/addfunctions2gvf.py +++ b/bin/addfunctions2gvf.py @@ -70,6 +70,7 @@ def add_template_annotations(gvf, annotation_file, annotation_resource): df['citation'] = df['author'] + ' et al. (' + df['publication_year'].str.replace(".0", "", regex=False) + ')' df_columns = functional_attributes + ["original_mutation_description", "protein_symbol"] df = df[df_columns] + df = df.drop_duplicates() merged_df = pd.merge(gvf, df, on=['original_mutation_description', 'protein_symbol'], how='left') #, 'alias' From 76f7ba04db2a334022f871f6b901cc9c6889f41b Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 12 Nov 2024 17:09:43 -0800 Subject: [PATCH 091/161] solve extra quotes issue --- bin/convert_pokay_to_virusmvp.py | 4 +++- 1 file changed, 3 insertions(+), 1 deletion(-) diff --git a/bin/convert_pokay_to_virusmvp.py b/bin/convert_pokay_to_virusmvp.py index 80178198..8da78b43 100755 --- a/bin/convert_pokay_to_virusmvp.py +++ b/bin/convert_pokay_to_virusmvp.py @@ -58,6 +58,8 @@ def data_cleanup(dframe): 'variant functional effect description'].str.replace(',#', '') dframe['variant functional effect description'] = dframe[ 'variant functional effect description'].str.replace('#', '') + dframe['variant functional effect description'] = dframe[ + 'variant functional effect description'].str.replace('"', "'", regex=False) dframe['variant functional effect description'] = dframe[ 'variant functional effect description'].str.strip() @@ -413,7 +415,7 @@ def write_tsv(dframe): # perform groupby and aggregation merged_dataFrame = merged_dataFrame.groupby(by=['index1'], as_index=False).agg(agg_dict) - #remove strings of commas in mutation name columns + # remove strings of commas in mutation name columns for column in ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias']: merged_dataFrame.loc[merged_dataFrame[column].str.contains(',,', regex=False), column] = '' merged_dataFrame.loc[merged_dataFrame[column]==',', column] = '' From 1c2cd51bd0af575beccc60c57f2957d1978b11c3 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 12 Nov 2024 17:44:20 -0800 Subject: [PATCH 092/161] add updated functional annotation file --- ...kay_functionalAnnotation_SARSCoV2_v4.0.tsv | 1388 +++++++++++++++++ 1 file changed, 1388 insertions(+) create mode 100644 assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.0.tsv diff --git a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.0.tsv b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.0.tsv new file mode 100644 index 00000000..8838d515 --- /dev/null +++ b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.0.tsv @@ -0,0 +1,1388 @@ +"organism" "reference accession" "reference database name" "nucleotide position" "original mutation description" "nucleotide mutation" "amino acid mutation" "amino acid mutation alias" "gene name" "gene symbol" "protein name" "protein symbol" "measured variant functional effect" "inferred variant functional effect" "viral life cycle functional effect" "variant functional effect description" "CVX code" "DrugBank Accession Number" "Antibody Registry ID" "author" "publication year" "URL" "DOI" "PMID" "peer review status" "curator" "mutation functional annotation resource" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has a 0.66x fold change in EC50 value with Remdesivir." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "viral load" "" "" "This mutant causes a 0.41x fold change in the infectious virus production rate." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has a 0.27x fold change in EC50 value with Remdesivir." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has an inhibition rate of virus production by Remdesivir of 0.80." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has an inhibition rate of virus production by Remdesivir of 0.78." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "viral load" "" "" "This mutant causes a 0.48x fold change in the infectious virus production rate." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.526 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed 3.8x reduction in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,22992,23012,23664" "L5F,S477N,E484K,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 114 test-positive were Iota. Two dose vaccine efficacy against Iota was 95.7 (81.7-99.0%), one dose VE was 88.8 (0.7-98.7)%." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,25186" "L5F,Q1208H" "NC_045512.2:g.13C>T,NC_045512.2:g.3624G>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Gln1208His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Four of the convalescent sera tested showed 4-fold or greater improvement in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21587" "P9S" "NC_045512.2:g.25C>T" "YP_009724390.1:p.Pro9Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2M28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21597" "S12F" "NC_045512.2:g.35C>T" "YP_009724390.1:p.Ser12Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "A variant in low % circulation, predicted to have a similar effect to the experimentally verified S12P, which introduces a new signal peptide, altering cleavage to occur between residues C15 and V16, thereby eliminating the C15-C136 disulfide bond – similarly to escape mutants at positions C15 and C136. This in turn decreases to varying degrees N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600" "S13I" "NC_045512.2:g.38G>T" "YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The S13I mutation dampened binding of 5 mAbs and abrogated binding of 5 additional mAbs out of 11 neutralizing mAbs evaluated. Predicted to shift the signal peptide cleavage site from S13-Q14 to C15-V16, which can affect NTD conformation. PG: in saying S12F does not shift the signal peptide nor affect mAb binding, this manuscript appears to contradict the text of McCallum et al.'s earlier 2021 manuscript stating that S12F *does* affected some mAb binding via putative signal peptide shift." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018" "S13I,W152C" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The B.1.427/B.1.429 S13I/W152C NTD did not bind to any NTD-directed neutralizing mAbs, which are known to target a single antigenic site (antigenic site i), whereas binding of the non-neutralizing S2L20 mAb to the NTD antigenic site iv was not affected by any mutants, confirming proper retention of folding." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Lineages bearing these spike mutations comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the 'California' or 'West Coast' variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI:1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020." "" "" "" "Peng" "2021" "https://doi.org/10.1093/cid/ciab283" "doi:10.1093/cid/ciab283" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 9 plasma collected 15 to 28 days after early 2020 infections, neutralization reduced 4.9-fold for B.1.427/B.1.429 compared to wildtype (D614G). In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.427/B.1.429 pseudotyped virus, as well as WT and other VOCs." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Swab samples N/NP viral RNA is approximately 2-fold higher in B.1.427/B.1.429 than in non-variant viruses." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "14 of 34 RBD-specific mAbs showed reduced neutralization to the B.1.427/B.1.429 variant pseudotype." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Antibody neutralization assays showed 6.7-fold resistance against 7/8 convalescent plasma." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.249 (1.7-fold). Neutralization against 10 convalescent plasma was somewhat poorer (3.1-fold)." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using HIV pseudotype: Neutralization potency of 11 Moderna mRNA1273-elicited plasma (7-27 days post-2nd dose) was reduced ~2.8-fold compared to wildtype (D614G) S. It was reduced ~4-fold in 14 Pfizer/BioNtech BNT162b2-elicited plasma (7-27 days post-2nd dose). Using VSV pseudotype: we observed a 3-fold average reduction of Pfizer/BioNtech BNT162b2-elicited plasma neutralizing activity." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "6 of 11 (55%) vaccine recipients (Moderna or Pfizer), showed 2x reduction in neutralization to a B.1.429 lineage virus." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.427/429 reduced 2.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 2.7x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 2.3x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403,25135" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G,K1191N" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3573G>T" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys1191Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for CAL.20C (B.1.429), and a slight decrease in CD8+ percentage (p=0.0201) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21604,21604" "Q14H,Q14H" "NC_045512.2:g.42G>C,NC_045512.2:g.42G>T" "YP_009724390.1:p.Gln14His,YP_009724390.1:p.Gln14His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21605" "C15R" "NC_045512.2:g.43T>C" "YP_009724390.1:p.Cys15Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21606" "C15F" "NC_045512.2:g.44G>T" "YP_009724390.1:p.Cys15Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite 'i', but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates neutralization by N-terminal-domain-targeting mAbs 4-19. Impairs neutralization by N-terminal-domain-targeting mAbs 4A8 and 2-17." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggetsing that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132" "L18F,T20N,P26S,D138Y,R190S" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The neutralization titer of NTD-binding mAb159 was 133-fold reduced on P.1 compared to Victoria (~wild type), with only 64% neutralization at 10 μg/mL. Residues 20, 18, and 138 form a cluster underlying the 245–259 loop, which inserts into a groove between the light and heavy chains of Fab 159. In addition, the N-terminal residues preceding residue 18 interact with the antibody and may be perturbed. Given that there is likely a single supersite ('i') for potent NTD-binding antibodies, the binding of many of these are likely affected. Using 20 potent (primaruly anti-RBD) antibodies, neutralization was measured by a focus reduction neutralization test (FRNT) and compared with neutralization of Victoria (~wild type) and variants B.1.1.7 and B.1.351. Compared to Victoria neutralization by the mAbs was significantly impacted by P.1, with 12/20 showing > 10-fold reduction in FRNT50 titer and a number showing complete knockout of activity. The results with P.1 showed a greater impact compared to B.1.1.7 but were, as expected, similar to those with B.1.351." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 12 Moderna vaccinee sera 15 days post second dose (43 days since first vaccination), an average 2.8x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 4.8x decrease against the full P.1 type vs WA-1 was observed, though overall with a higher ID50 reciprocal value. In 10 Pfizer vaccinee sera 7 days or more post second dose (28 days or more since first vaccination), an average 2.2x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.8x decrease against the full P.1 type vs WA-1 was observed, with similar variant ID50 reciprocal value." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the “up” position." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Amongst RBD-targeting Emergency Use Authorized monoclonal antibody treatments CB6, LY-CoV555 and REGN10933 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1, but REGN10987 activity remains strong. RBD-targeting monoclonal antibodies 2-15 and C121 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. N terminal domain targeting monoclonal antibodies 5-7, 4-8, 4-18 and 2-17 have abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In convalescent sera one month or more post-infection in Spring 2020, an average 6.5x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.4x decrease against the full P.1 type vs WA-1 was observed, with better full P.1 ID50 reciprocal value compared to the 10-mutation model." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Three healthcare workers (29-50yo) had confirmed P.1 [Gamma] re-infection in the Amazonas region of Brazil 3-9 months after initial infection from viruses with distinct lineage from P.1, but mild symptoms upon re-infection and evidence for infectiousness during re-infection." "" "" "" "Naveca" "2021" "https://doi.org/10.21203/rs.3.rs-318392/v1" "doi:10.21203/rs.3.rs-318392/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "After a 128 day interval, a patient in Sao Paulo State, Brazil reinfected with P.1 (first episode likely predates P.1 emergence). Both cases were fairly mild (difficulty breathing, tiredness, dizziness and fatigue)." "" "" "" "Malta Romano" "2021" "https://doi.org/10.1590/S1678-9946202163036" "doi:10.1590/S1678-9946202163036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 3.0x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 349 test-positive were Gamma. Two dose vaccine efficacy against Gamma was 95.5 (90.9-97.8%), one dose VE was 74.2 (43.8-88.1%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Gamma (P.1) variant is 0.6x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 4.1x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x cleavage of S2 relative to WA1 (D614G) wildtype by Gamma variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but H655Y is upstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.7 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0039 for mild resistance." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Unlike wild type or B.1.1.7, P.1 lineage virus was able to infect and replicate in common lab mouse strains, with high titer." "" "" "" "Montagutelli" "2021" "https://doi.org/10.1101/2021.03.18.436013" "doi:10.1101/2021.03.18.436013" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.248 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07. B.1.1.248 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.248 variant constellation in 10 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples, P=0.0020." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly lower against B.1.1.248 variant constellation in sera tested from most of the 15 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 16.6% in this B.1.1.248 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped P.1 virus has reduced neutralization activity vs wild type: 6.7x (30 sera Pfizer median 9 days post 2nd dose) and 4.5x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Among 46,884 HCWs in Manaus, Brazil vaccinated with at least one dose of CoronaVac, a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%; 95% CI, 11.3 - 71.4) in the odds of symptomatic SARS-CoV-2 infection was observed during the period 14 days or more after receiving the first dose. Estimated vaccine effectiveness of at least one dose against any SARS-CoV-2 infection was 35.1% (95% CI, −6.6 - 60.5) in the same time period." "" "" "" "Hitchlings" "2021" "https://doi.org/10.1101/2021.04.07.21255081" "doi:10.1101/2021.04.07.21255081" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for P.1 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the P.1 variants used, using the most popular as a stand in]" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "VSV pseudotype P.1 showed 4.8-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections)." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype P.1 showed slight decrease in cell entry relative to wild type in 262T and 263T-ACE2 (kidney) cell lines. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Neutralizing antibodies that were generated following a mild infection with SARS-CoV-2 B.1.128 were effective in vitro, and likely protective, against the SARS-CoV-2 P.1. variant in the majority of individuals based on 60 convalescent sera tested." "" "" "" "Mendes-Correa" "2021" "https://doi.org/10.1101/2021.05.11.21256908" "doi:10.1101/2021.05.11.21256908" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.15x *increase* in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "VSV pseudotype P.1 entry mediated by the S proteins of the P.1 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Cell fusion proficiency was slight impaired. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "P.1 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with Lilly mAb combination LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of P.1. There was also escape from neutralization of P.1 by REGN10933 (one of 2 in Regeneron's mAb cocktail) and a modest reduction in neutralization of P.1 by AstraZeneca's AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized P.1 with all reaching a plateau at 100% neutralization; interestingly, ADG30 showed a slight increase of neutralization of P.1. S309 Vir was largely unaffected, although for several viruses, including P.1, the antibody failed to completely neutralize, conceivably reflecting incomplete glycosylation at N343, since the sugar interaction is key to binding of this antibody." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "PBMCs of 11 mild COVID-19 patients collected 38-80 days after symptom onset were stimulated with the 15-mer peptide pools (w/ 10 residue overlaps) from the wholle viral proteome, showing no significant CD4+ cell count effect for P.1, and a slight increase in CD8+ percentage (p=0.0195) by Activation Induced Marker (AIM) assay (cellular immunity measurement). [in the text, this increase is not noted as signficant, even though p=0.05 is used elsewhere in the text as a signficance threshold]" "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against P.1 at various time points using pseudovirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 85%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 256 for B.1.1.7 virus. Compare to somewhat stronger neutralization titer for wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The relative transmissibility of P.1 estimated at the national level (Italy) varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. PG: variant list has been abbreviated due to mixed K417 bases in this lineage, potential miscalls of deletions" "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21762,21763,21764,21765,21766,21766,21761,21801,22206,22334,22600,22600,22810,22811,22812,22813,22813,22879,22881,22882,22882,22986,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,H69del,H69del,H69del,H69del,H69del,H69del,V70del,D80A,D215G,W258R,R346S,R346S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,A475V,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.772T>C,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1424C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ala475Val,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments and mutations from variants of concern completely ablates neutralization in 19 of 21 convalescents plasma collected mean 1.3 months post infection. [actual Y145del from manuscript substituted with more common Y144del description]" "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801" "L18F,D80A" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The L18F and D80A of the B.1.351 lineage lead to reconfiguration of the N-terminal segment despite the disulfide between Cys16 and Cys136 that partly anchors the N-terminal peptide. The most consequential changes are probably from the triple residue deletion... which causes a shift of the nearby loop 144-155 and must also reconfigure the adjacent disorder loop (residues 246-260), both of which form part of the neutralizing epitopes...bringing large changes in the antigenic surface in this region." "" "" "" "Cai" "2021" "https://doi.org/10.1101/2021.04.13.439709" "doi:10.1101/2021.04.13.439709" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The 501Y.V2 to first wave IC50 ratio ranged from 6 to 200-fold. Averaging across all 7 participant convalescent sera highlighted the dramatic decrease in sensitivity to neutralization of authentic 501Y.V2 variants. PG: I'm purposefully ignoring D614G and A701V as contributors" "" "" "" "Cele" "2021" "https://doi.org/10.1038/s41586-021-03471-w" "doi:10.1038/s41586-021-03471-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike)." "" "" "" "Riddell" "2021" "https://doi.org/10.1101/2021.04.17.440246" "doi:10.1101/2021.04.17.440246" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pzifer vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1), but were all infected before 14 days post second vaccination." "" "" "" "Kustin" "2021" "https://doi.org/10.1101/2021.04.06.21254882" "doi:10.1101/2021.04.06.21254882" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~7-fold reduction in B.1.351 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "B.1.351 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of B.1.351. There was also escape from neutralization of B.1.351 by REGN10933 and a modest reduction in neutralization of B.1.351 by AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized B.1.351." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.07x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "[Contrary to how this paper has been cited, Voysey et al. do NOT show evidence of decreased effectiveness of ChAdOx1 (AstraZeneca) against the South African B.1.351 lineage. Insufficient numbers reaching the primary study endpoint were available in that arm of the vaccine study to report any statistics from the South African participants. Additionally, the study period of the paper ended in November 2020, while the earliest reported case of this lineage is October (covariants.org), only becoming dominant by mid-November.]" "" "" "" "Voysey" "2021" "https://doi.org/10.1016/S0140-6736(20" "doi:10.1016/S0140-6736(20" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 0.036x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR22 molecule had a 1.57x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.054x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.351 sample. Contrast this with 1.4-fold reduction for just the pseudovirus combination of 'key' B.1.351 mutations K417N+E484K+N501Y. WA1 and B.1.351 FRNT50 titers correlated weakly at the individual level, with some individual’s serum potently neutralizing WA1 while having FRNT50 for B.1.351 below the assay limit of detection (1:20)." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v2 virus has reduced neutralization activity vs wild type: 41.2x (30 sera Pfizer median 9 days post 2nd dose) and 20.8x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed for B.1.351 a CD4+ cell count decrease (29%, p=0.00063) as well as CD8+ (33%, p=0.0016) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Beta neutralizing antibodies is 0.899x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: while B.1.1.7 and D614G showed neutralization by nasal swab from only one different previously infected vacinee neutralizing at weeks 3 and 6, B.1.351 showed zero neutralization at either time point in any sample (and relatively impaired serum neutralization)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Beta neutralizing antibodies is 0.803x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Beta Variant B.1.351 RBD significantly better than w.t. SARS-CoV-2 RBD. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals (5/9) and recipients of a only a single dose of mRNA vaccine (10/11) – heterotypic neutralization dropped to negligible levels, particularly against B.1.351." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "A 1.8-fold drop in FRNT50 for B.1.351 was observed in 44 sera collected between 1 and 301 post-infection." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "3.2x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 6.3x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Encouragingly, we find that the majority of T cell responses in recipients of two doses of the BNT162b2 vaccine are generated by epitopes that are invariant between the [wildtype] and two of the current variants of concern (B.1.1.7 and B.1.351). In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals and recipients of a only a single dose of mRNA vaccine – heterotypic neutralization dropped to negligible levels, particularly against B.1.351." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 16/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.351, with similar results for the live virus." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.351. We observed an increase (relative to D614G) in binding of soluble ACE2 to B.1.351, and to a much gearter extent to B.1.1.7, which both carry the N501Y mutation (see Fig 3)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Sera from individuals who have been infected with Delta does not have strong neutralising activity against Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 8 for B.1.351 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Pseudotype lentivirus for the full B.1.351 Spike variant list shows increase affinity for ACE2 as measured by IC50. This is in contrast to B.1.1.7 which showed no major change, indicating that the shared N501Y mutation is the driver of affinity change, attentuated in the B.1.1.7 mutatioon set, but maintained in the B.1.351 lineage." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 8.2x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.351 pseudotyped virus model ablates neutralization by RBD-directed mAbs CB6, 4-20, 2-4, 2-43, 910-30, 2-302-15, LY-Cov555, C121. B.1.351 pseudotyped virus model severely impairs neutralization by RBD-directed mAb 1-20. B.1.351 pseudotyped virus model impairs neutralization by RBD-directed mAb REGN10933. B.1.351 pseudotyped virus model ablates neutralization by N-terminal-domain-directed mAbs 5-24, 4-8, 4A8, 4-19. B.1.351 pseudotyped virus model severely impairs neutralization by N-terminal-domain-directed mAb 2-17. B.1.351 pseudotyped virus model impairs neutralization by N-terminal-domain-directed mAb 5-7. PG: Live virus data for the same mAbs is similar, but 1-20 becomes severally impaired, REGN10933 activity is ablated, and Brii-196 becomes impaired." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v2 reduced 7.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms had mean ~6x reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 99.7x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 6.7x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with all key mutations from B.1.351 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting some synergy between the mutations to decrease cell entry fitness (i.e. cell entry is liklely not the driver of this lineage's dominance)." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,23060,23061,23062,23063,22810,22811,22812,22813,22813,23012,23399,23401,23402,23403" "L18F,D80A,D215G,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The most significant loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against authentic B.1.351 lineage virus (9.2-fold). Neutralization against 10 convalescent plasma was poorer (18.7x)." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks." "" "" "" "Meister" "2021" "https://doi.org/10.1093/infdis/jiab260" "doi:10.1093/infdis/jiab260" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Parana state of Brazil, patients aged 20-29 years experienced a tripling of their case fatality rate (CFR), from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling comparing February to January in 2021. Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil. [this is somewhat indirect evidence that assume greatly increasing proportion of P.1 cases in March (70%) compared to February, but the first official ID of P.1 in Parana state (Feb 16th) may be due to testing procedures rather than actual prevalence]" "" "" "" "Santos de Oliviera" "2021" "https://doi.org/10.1101/2021.03.24.21254046" "doi:10.1101/2021.03.24.21254046" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22915,22916,22917,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 (Pfizer) vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains." "" "" "" "Mallm" "2021" "https://doi.org/10.1101/2021.04.27.21254849" "doi:10.1101/2021.04.27.21254849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Delta (B.1.617.2) shows mean 2.1x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Delta (B.1.617.2) shows 3.64x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22916,22917,23012,23399,23401,23402,23403" "T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this lineage defining mutation combination from B.1.617.3 conferred a ~4.5x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22916,22917,23012,23399,23401,23402,23403" "T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this lineage defining mutation combination from B.1.617.3 conferred a ~11.8x drop in neutralization (NT50) [suggesting role for T19R and T95I in half the sera]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22916,22917,23012,23399,23401,23402,23403" "T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this lineage defining mutation combination from B.1.617.3 increased syncytium formation ~2.3x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,23399,23401,23402,23403" "T19R,T95I,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23604,23399,23401,23402,23403,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,P681R,D614G,D614G,D614G,D614G,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4.5x cleavage of S2 relative to WA1 (D614G) wildtype by Delta (B.1.617.2) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~3.5x for closely related Kappa B.1.617.1 also with P681R at the cleavage site)." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 ('Kappa') reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. [Mutation list in publication appears to contain a typo with R158del instead of R158G]" "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 4.0x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Modelling the Delta variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increased 11x relative to wild type (15.3 vs 1.4). [del ~157 truncated due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a coinfection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.020x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 2.6x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.10x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In primary human airway epithelial cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 1.9x relative to wild type (2.7 vs 1.4). This is the Delta variant with the P681R furin cleavage site mutation absent. [del ~157 truncated due to ambiguity]" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Plasma neutralizing activity was also assessed against SARS-CoV-2 Delta, Omicron BA.1, BA.2 and BA.4/5 variants using viruses pseudotyped with appropriate variant spikeproteins. Delta breakthrough infection resulted in 15-fold increased neutralizing titers." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Delta neutralizing antibodies is 0.872x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Delta neutralizing antibodies is 0.952x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Plasma neutralizing activity in 49 participants was measured using HIV-1 pseudotyped with the 100 WT SARS-CoV-2 spike protein. Delta breakthrough infection resulted in 11-fold increased geometric mean half-maximal neutralizing titer (NT50)." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Delta Variant B.1.617.2 RBD or w.t. SARS-CoV-2 RBD with nearly equal potency determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 507 pM for binding to the Delta B.1.617.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.92x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001)." "" "" "" "Chia" "2021" "https://doi.org/10.1101/2021.07.28.21261295" "doi:10.1101/2021.07.28.21261295" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "The incidence rate of Covid-19 during the Delta-dominant period (Jul-Aug 2021) was lower for late vaccinated (49.0/1000 person-years) [formerly placebo] versus early vaccinated (77.1/1000 person-years) participants in the Moderna mRNA-1273 Phase 3 trials, representing a 36.4% VE reduction (95% CI 17.1%-51.5%). There were fewer severe Covid-19 cases in the late group (6; 6.2/1000 person-years) than early (13; 3.3/1000 person-years), representing a 46.0% reduction (95% CI −52.4%-83.2%). Three Covid-19 related hospitalizations occurred with two resulting deaths in the early group." "" "" "" "Baden" "2021" "https://doi.org/10.1101/2021.09.17.21263624" "doi:10.1101/2021.09.17.21263624" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccination of health care workers in Delhi was started in early 2021, with the ChdOx-1 (Astra Zeneca) vaccine. Surveillance has suggested B.1.1.7 dominance in the Delhi area during early 2021, with growth of B.1.617 since March 2021. During the wave of infections during March and April an outbreak of SARS-CoV-2 was confirmed in 33 vaccinated staff members at a single tertiary centre (age 27-77 years). Sequencing revealed that 16/33 were B.1.617.2, with a range of other B lineage viruses including B.1.1.7 for the rest except one A lineage case. Importantly no severe cases were documented in this event." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.2 aka Delta) showed a 2.34x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance." "" "" "" "Twohig" "2021" "https://doi.org/10.1016/S1473-3099(21" "doi:10.1016/S1473-3099(21" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Denmark, for the period Jan 1 to Jun 27, 2021, Delta variant was associated with increased an risk ratio of 2.83 [95% CI 2.02–3.98] for hospitalization." "" "" "" "Bager" "2021" "https://doi.org/10.1016/S1473-3099(21" "doi:10.1016/S1473-3099(21" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.89x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Delta Molnupiravir (MK-4482) had ~4x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Case 62541 cluster in Singapore included a fully vaccinated nurse 2 months post-vaccine [likely Pfizer based on dates and supply], and a doctor of unknown vaccine status. This cluster was caused by a B.1.617.2 virus [via crossreference to" "" "" "" "" "" "nan" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Delta (B.1.617.2) has an IC50 fold change of 46.5x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Delta (B.1.617.2) has an IC50 fold change of 0.15x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Delta (B.1.617.2) has an IC50 fold change of 0.57x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Delta (B.1.617.2) has an IC50 fold change of 0.87x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Delta (B.1.617.2) variant is 0.6x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,23399,23401,23402,23403" "T19R,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21627" "T22I" "NC_045512.2:g.65C>T" "YP_009724390.1:p.Thr22Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain, frequently observed in various human infection lineages, reduces the tropism of SARS-CoV-2 in F81 (cat kidney, Felis catus) and BHK-21 (golden hamster kidney, Mesocricetus auratus) cell line cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21648" "T29I" "NC_045512.2:g.86C>T" "YP_009724390.1:p.Thr29Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21717,21762,21763,21764,21765,21766,21766,21761,23012,23399,23401,23402,23403,23593,23593,24224" "Q52R,H69del,H69del,H69del,H69del,H69del,H69del,V70del,E484K,D614G,D614G,D614G,D614G,Q677H,Q677H,F888L" "NC_045512.2:g.155A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C" "YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.525 reduced 4.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21717,23012,23593,23593,24224" "Q52R,E484K,Q677H,Q677H,F888L" "NC_045512.2:g.155A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C" "YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The B.1.525 appears to have poor transmissibility when in competition with B.1.1.7 and other circulating strains in Denmark (early 2021)." "" "" "" "Albertsen" "2021" "https://www.covid19genomics.dk/2021-05-08_data-overview.html#b1525" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21752,21752" "W64R,W64R" "NC_045512.2:g.190T>A,NC_045512.2:g.190T>C" "YP_009724390.1:p.Trp64Arg,YP_009724390.1:p.Trp64Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21759" "H66R" "NC_045512.2:g.197A>G" "YP_009724390.1:p.His66Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent, especially on a D614 wildtype background." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduces neutralization by structurally unmapped mAb COVA1-21 (cluster XI)." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No notable change in neutralization efficiency, despite N439K by itself showing a ~2x decrease on average in 16 health workers' convalescent sera." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This deletion outside the receptor binding domain in pseudotyped VSV promoted the capacity of pseudotyped VSV to transduce black flying fox (Pteropus alecto) kidney PabKi.1 cells (17.8%) to a level twice that of human epithelial-like Huh-7 cells (9.8%)" "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization activity of almost all convalescent sera tested decreased ~2x." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization activity of convalescent sera tested decreased ~2x with this B.1.1.7 pseudotyped virus." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Neutralization activity of almost all Moderna Phase 1 sera tested actually *increased*." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "The delH69/V70 enhances viral infectivity, indicating its effect on virus fitness is independent to the N501Y RBM change [with which it is found in lineage B.1.1.7] Possibly arisen as a result of the virus evolving from immune selection pressure in infected individuals and possibly only one chronic infection in the case of lineage B.1.1.7." "" "" "" "Kemp" "2020" "https://doi.org/10.1101/2020.12.14.422555" "doi:10.1101/2020.12.14.422555" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron (a.k.a. B.1.1.529) Spike pseudotyped VSV and Vero E6 cells has somewhat reduced neutralization (2.7x) vs wild type with monoclonal antibody Sotrovimab (a.k.a. VIR-7831). [delins at 214 omitted for syntax compatibility]" "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron breakthrough infection after 3-dose vaccination resulted in a further 3.5-fold and 2.9-fold increase of Omicron BA.1 and BA.2 neutralizing titers. Omicron BA.4/5 showed the highest neutralization resistance of all variants tested, resulting in low geometric mean neutralizing titers in plasma samples obtained after the second vaccine dose (NT50=72)." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Delta variant and was used to determine neutralizing antibodytitres. There was a 24.63x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 4.21x fold increase in antibody response pre-reinfection. There was a 39.27x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against B.1 variant and was used to determine neutralizing antibodytitres. There was a 6.76x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 2.06x fold increase in antibody response pre-reinfection. There was a 8.18x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron B.1.1.529 (BA.1) neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Omicron BA.1 variant is 1.0x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigms’ ACE-2 variant LVE/STR chimera binds to SARS-2 Omicron variant B.1.1.529 spike protein trimer with high affinity. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Omicron BA.1 has an IC50 fold change of 0.38x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 73 pM for binding to the Omicron B.1.1.529. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron (B.1.1.529 [BA.1]) have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "All 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 729 NT50." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "All 10 individuals with 3 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 3319 NT50." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.1 has an IC50 fold change of 0.30x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Omicron BA.1 has an IC50 fold change of 1.26x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Omicron variant and was used to determine neutralizing antibodytitres. There was a 114.84x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 6.61x fold increase in antibody response pre-reinfection. There was a 1194.9x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.1 has an IC50 fold change of 0.08x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.3 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.3 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was somewhat lower against B.1.1.7 in sera tested from most of the 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.7 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2489." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.1.7 sample. Contrast this with 1.3-fold reduction for just the pseudovirus combination of 'key' B.1.1.7 mutation N501Y." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing moderate decrease in infection rate amongst the cells, significantly lower than the deletion or Y453F alone, or their combination, suggesting a synergistic effect on poorer human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild to modest decrease in infection rate amongst the cells, suggesting a net mild negative effect on human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, much closer to D614G activity level than Y453F alone, suggesting compensatory effects between the deletion and the mutation in human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920,23399,23401,23402,23403,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F,D614G,D614G,D614G,D614G,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.298 virus has reduced neutralization activity vs wild type: 1.4x (30 sera Pfizer median 9 days post 2nd dose) and 1.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from Mink Cluster 5 was neutralized more easily than D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with all key mutations from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (~50%) decrease in infection rate amongst the cells, suggesting that this anthropozoonotic event is driven by other factors at the expense of human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells, markedly higher infectivity than either mutation alone, suggesting a synergistic net neutral effect on human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7+E484K reduced 2.8x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Compare with 1.2x reduction for B.1.1.7 without E484K." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization capacity GMT of 27 subjects' sera post-infection was markedly worse against B.1.1.7 + E484K than the lineage alone, with a 11.4x drop." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "In comparison of B.1.1.7 lineage (193 cases) vs. 'wildtype' (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." "" "" "" "van Loon" "2021" "https://doi.org/10.1101/2021.04.15.21255389" "doi:10.1101/2021.04.15.21255389" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "A higher proportion of cases infected with the B.1.1.7 variant were hypoxic on admission compared to other variants (70.0% vs 62.5%, p=0.029), in London between March 13th 2020 and February 17th 2021 (400 B.1.1.7 cases out of 1470 total sequenced)." "" "" "" "Snell" "2021" "https://doi.org/10.1101/2021.03.16.21253377" "doi:10.1101/2021.03.16.21253377" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x). PG: these effects are laregly missing in the deletion-alone data" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation combination causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, moreso than this combination with the addition of P681H." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020. Possible reinfections were identified in 249 (0.7% [95% CI 0.6-0.8]) of 36509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants." "" "" "" "Graham" "2021" "https://doi.org/10.1016/s2468-2667(21" "doi:10.1016/s2468-2667(21" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "https://doi.org/10.1016/S0140-6736(21" "doi:10.1016/S0140-6736(21" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion)." "" "" "" "Marquez" "2021" "https://doi.org/10.1017/ice.2021.195" "doi:10.1017/ice.2021.195" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "https://doi.org/10.1016/S0140-6736(21" "doi:10.1016/S0140-6736(21" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Second infection in December 2020 with B.1.1.7 after April 2020 initial infection with B.2 in a 78-year-old man with a history of Type 2 diabetes mellitus, diabetic nephropathy on hemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnea, ischemic heart disease, with no history of immunosuppression." "" "" "" "Harrington" "2021" "https://doi.org/10.1093/cid/ciab014" "doi:10.1093/cid/ciab014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Alpha (B.1.1.7) variant is 1.0x fold the wildtype in 42 COVI." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.1.7. We observed a dramatic increase (relative to D614G) in binding of soluble ACE2 to B.1.1.7, and to a lesser extent to B.1.351, which both carry the N501Y mutation (see Fig 3)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "https://doi.org/10.1016/S0140-6736(21" "doi:10.1016/S0140-6736(21" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "https://doi.org/10.1016/S0140-6736(21" "doi:10.1016/S0140-6736(21" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks." "" "" "" "Meister" "2021" "https://doi.org/10.1093/infdis/jiab260" "doi:10.1093/infdis/jiab260" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively." "" "" "" "Schuit" "2021" "https://doi.org/10.1093/infdis/jiab171" "doi:10.1093/infdis/jiab171" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Alpha (B.1.1.7) has an IC50 fold change of 1.19x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Alpha Molnupiravir (MK-4482) had ~2.75x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaulated against VSV pseudotypes: neutralized D614G at week 2, whereas B.1.1.7 started to be neutralized at week 3, although less efficiently than D614G. B.1.1.7 and D614G strains were similarly neutralized at week 4 (1 week after booster dose)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the 47D10. Alpha (B.1.1.7) has an IC50 fold change of 0.40x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2.5x cleavage of S2 relative to WA1 (D614G) wildtype by Alpha variant variant as measured by mass spectrometry of Vero-TMPRSS culture." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.39x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "NTD-specific nAbs showed a substantial (3-450x) decrease in neutralization potency against the recently reported highly transmissible B.1.1.7 variant of concern, whereas RBD-specific nAbs were either unaffected or showed lower decreases in potency." "" "" "" "Graham" "2021" "https://doi.org/10.1016/j.immuni.2021.03.023" "doi:10.1016/j.immuni.2021.03.023" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20x resistence to mAb CQ038 by B.1.1.7 pseudotyped virus" "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 2/20 (10%) samples showed >10x reduction (sera collected ~1mo post Jan 2020 first wave in China). Neutralizing antibody titers of 8/20 samples (40%) decreased below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM for binding to the Alpha B1.1.7. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 2.6x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Lessens the potency of mAbs COVA2-17 (~5x, similar to N501Y alone), COVA1-12 (~11x) and COVA1-21 (>100x), which do not compete allosterically." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.7 pseudotyped virus model impairs binding by RBD-directed mAb 910-30. B.1.1.7 pseudotyped virus model abolishes N-terminal-domain-directed mAbs 5-24, 4-8, and 4A8. B.1.1.7 pseudotyped virus model impairs binding by N-terminal-domain-directed mAbs 2-17, 4-19, 5-7." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%)." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Modelling the Alpha variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 3.9x relative to wild type (5.4 vs 1.4). This is less efficient than Delta (11x vs wildtype using a P681R mutation instead). [del ~144 changed due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a co-infection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization assays of B.1.1.7 virus showed a reduction of 2.5-fold (14 days post 2nd dose AstraZeneca, n=15), 2.1-fold (28 days post 2nd dose AstraZeneca, n=10), and 3.3-fold (7-17 days post 2nd dose Pfizer-BioNTech, n=25). [D1119H was included in the original paper, assumed typographical error and changed to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 1 (B.1.1.7) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 virus has reduced neutralization activity vs wild type: 2.1x (30 sera Pfizer median 9 days post 2nd dose) and 2.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Note that Y145del was actually noted in the paper as the effect of their DNA construct, but this is equivalent at the protein level to the more commonly annotated Y144del." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM analysis of B.1.1.7 demonstrates an increased propensity for 'up', receptor accessible conformation of the Spike protein trimer." "" "" "" "Cai" "2021" "https://doi.org/10.1101/2021.04.13.439709" "doi:10.1101/2021.04.13.439709" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Alpha Variant B.1.1.7 RBD significantly better than GenScript IgG FL18-740 w.t. ACE-2 mAB. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "NVX-CoV2373 [Novavax] vaccine in phase 3 trial was 89.7% (95% CI, 80.2-94.6) effective in preventing COVID-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8-99.5) and 86.3% (71.3-93.5) against the prototype strain and B.1.1.7 variant, respectively." "" "" "" "Heath" "2021" "https://doi.org/10.1101/2021.05.13.21256639" "doi:10.1101/2021.05.13.21256639" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Live virus was tested ex vivo in reconstituted brochial epithelium, and out competed wild type." "" "" "" "Touret" "2021" "https://doi.org/10.1101/2021.03.22.436427" "doi:10.1101/2021.03.22.436427" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 1.7x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "clinical indicators" "" "" "After adjusting for the age factor, in a prospective Chinese cohort study B.1.1.7 variant infection (compared to B.1.140) was the risk factor for C-reactive protein (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), Serum amyloid A (0.011, 5.031, [1.459, 17.354]), Creatine Kinase (0.034, 4.34, [0.05, 0.91]), CD4+ T lymphocyte (0.029, 3.31, [1.13, 9.71]), and Ground Glass Opacity (0.005, 5.418, [1.656, 17.729])" "" "" "" "Song" "2021" "https://doi.org/10.1101/2021.05.04.21256655" "doi:10.1101/2021.05.04.21256655" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "aerosolization" "" "" "Alpha variant cases in a large campus study showed fine-aerosol shedding amongst unmasked participants remained significantly greater for alpha variant infections (18-fold, 95% CI, 3.4 to 92-fold) after adjusting for the increased viral RNA in MTS and saliva, the number of coughs during sampling sessions, and symptom. After controlling for the effect of masks and numbers of coughs during sampling, alpha variant infection was associated with a 100-fold (95% CI, 16 to 650-fold) increase in coarse- and a 73-fold (95% CI, 15 to 350-fold) increase in fine-aerosol RNA shedding." "" "" "" "Adenaiye" "2021" "https://doi.org/10.1093/cid/ciab797" "doi:10.1093/cid/ciab797" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We observed a sharp decline in cases when ∼50% of the elderly population was 2 weeks beyond their first vaccination dose and at a time point during which the B.1.1.7 variant gained transmission dominance. In support of this finding, it was suggested that, after the first vaccination dose, more than 70% of patients develop neutralization antibodies,15 and the vaccine efficiency can reach 85%." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.44x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "First documented cases of domestic cat and dog infections with the B.1.1.7 strain." "" "" "" "Hamer" "2021" "https://doi.org/10.1111/tbed.14122" "doi:10.1111/tbed.14122" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "," "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.1.7 lineage effectiveness was observed as 29.5% (95% CI [22.9,35.5]) against infection, and 54.1% against severe/critical/fatal disease (95% CI [26.1-71.9]). Two weeks or more after 2nd dose, effectiveness climbed to 89.5% [85.9,92.3] against infection, and 100% against severe/critical/fatal disease (95% CI [81.7,100])." "" "" "" "" "" "," "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24506" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,S982A" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Lilly's LY-CoV16 showed marked reduction in neutralization of B.1.1.7." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Sera neutralized the B1.1.7 isolate with a lower potency (2-fold; 95% CL: 1.5 – 3-fold), and those with the lowest homotypic neutralizing potency had undetectable heterotypic potency (2/25)." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23709,23604,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,T716I,P681H,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific replication effects" "" "" "In this report, by using a lower infectious dose, we demonstrate that B.1.1.7 (cultured sample Hong Kong/HKPU-00015/2021) exhibits higher infectivity and/or replication efficiency in the nasal epithelium. (Hamster model of infection)" "" "" "" "Mok" "2021" "https://doi.org/10.1101/2021.04.19.440414" "doi:10.1101/2021.04.19.440414" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 'wild type' SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020, Rt of B.1.1.7 was 1.35x (95% CI 1.02-1.69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant." "" "" "" "Graham" "2021" "https://doi.org/10.1016/s2468-2667(21" "doi:10.1016/s2468-2667(21" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036)." "" "" "" "Song" "2021" "https://doi.org/10.1101/2021.05.04.21256655" "doi:10.1101/2021.05.04.21256655" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7." "" "" "" "Graham" "2021" "https://doi.org/10.1016/s2468-2667(21" "doi:10.1016/s2468-2667(21" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The mortality hazard ratio associated with infection with [B.1.1.7] compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community (54906 matched pairs of participants who tested positive for SARS-CoV-2 in pillar 2 between 1 October 2020 and 29 January 2021). In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases." "" "" "" "Challen" "2021" "https://doi.org/10.1136/bmj.n579" "doi:10.1136/bmj.n579" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "https://doi.org/10.1016/s1473-3099(21" "doi:10.1016/s1473-3099(21" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization capacity GMT of 27 subjects' sera post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies." "" "" "" "Muik" "2021" "https://doi.org/10.1126/science.abg6105" "doi:10.1126/science.abg6105" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "20/29 sera after the first dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 variant of 3.2 ± 5.7. After the second dose, the GMT was markedly increased compared with the first-dose titres, with a fold change of 1.9 ± 0.9 (mean ± s.d.). Neutralization GMT of 27 subjects post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "https://www.medrxiv.org/content/10.1101/2021.03.31.21254502v1" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype B.1.1.7 showed no significant difference in cell entry relative to wild type in 6 cell lines. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 ('UK variant'). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, but to a smaller extent than N501Y and the deletion alone." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Slight neutralization improvement on average in 16 health workers' convalescent sera." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "These key B.1.1.7 mutations as a combination neutralized slightly less well than D614G and this was noticeable in the lack of sera with high neutralizing titer for the viruses across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,23399,23401,23402,23403,22915,22916,22917" "H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 17.2x-fold lower (95% CI: 0.6x-0.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,23399,23401,23402,23403,22915,22916,22917" "H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 13.0-fold lower (95% CI: 4.2x-4.6x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,22810,22811,22812,22813,22813,23009,23010,23012,23013" "H69del,H69del,H69del,H69del,H69del,H69del,K417N,K417N,K417N,K417N,K417N,E484A,E484A,E484A,E484A" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario, using a retrospective matched case (age, gender and onset date) study of 6,312 Omicron cases vs 8,875 Delta, the adjusted risk of hospitalization or death was 54% lower (HR=0.46, 95%CI: 0.27, 0.77) among Omicron cases, after adjusting for vaccination statis and time since 2nd shot. The ratio for >60yo was 0.55 (95%CI: 0.28-1.06), and <60yo was 0.30 (95%CI: 0.16-0.57)." "" "" "" "Ulloa" "2021" "https://doi.org/10.1101/2021.12.24.21268382" "doi:10.1101/2021.12.24.21268382" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,23009,23010,23012,23013" "H69del,H69del,H69del,H69del,H69del,H69del,E484A,E484A,E484A,E484A" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection, evidenced by a reinfection hazard ratio of 2.39 (CI95: 1.88-3.11) relative to primary infection in the initial part of South Africa's 4th covid-19 wave (November 2021). In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. [minimal variant signature for Omicron (B.1.1.529) used based on H69del PCR dropout observed in November 2021 coincident with the rise of Omicron]" "" "" "" "Pulliam" "2021" "https://doi.org/10.1101/2021.11.11.21266068" "doi:10.1101/2021.11.11.21266068" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800" "D80N" "NC_045512.2:g.238G>A" "YP_009724390.1:p.Asp80Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800" "D80Y" "NC_045512.2:g.238G>T" "YP_009724390.1:p.Asp80Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This AA substitution outside the receptor binding domain in pseudotyped VSV promoted a 7.2% transduction rate in golden hamster cells, which was higher than that of human epithelial-like Huh-7 cells (6.6%)." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800,22188,22206,22597,22599,23012,23521,23522,23524,23525,23604" "D80Y,I210del,D215G,R346K,R346K,E484K,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.238G>T,NC_045512.2:g.629_631del,NC_045512.2:g.644A>G,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp80Tyr,YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.VOI.V2 (first identified in Angola) reduced 8.0x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "One individual of 30 in the study, with HLA supertype HLA*A24:02, had a linear epitope that overlaps this variant of concern." "" "" "" "Redd" "2021" "https://doi.org/10.1101/2021.02.11.21251585" "doi:10.1101/2021.02.11.21251585" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolishes neutralizing activity of N-terminal-domain-directed mAb 4-19." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated that there is no free energy change (ddG) for this variant (i.e. same stability as wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In an Ontario long term care facility, cumulatively, weaker BNT162b2 vaccine stimulation, age/comorbidities, produced a ∼130-fold reduction in apparent neutralization titers in mean 88yo LTCH residents against Beta (B.1.351), relative to staff vaccinees against D614G wild type. 37.9% of 116 two-dose-mRNA-vaccinated residents had undetectable neutralizing antibodies to B.1.351. mRNA-1273 vaccinee sera displayed ~2 better neutralization than BNT162b2. [common defining B.1.351 mutations noted, as the manuscript does not provide details]" "" "" "" "Abe" "2021" "https://doi.org/10.1101/2021.08.06.21261721" "doi:10.1101/2021.08.06.21261721" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, 7 of 15 neutralized this B.1.351 pseudotype that includes the L242del, and only one had titers above 100. Only one of the 15 sera achieved 80% neutralization. [compare to 5 and 1 for pseudotype without the deletion]" "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.351 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 71%, Day 209 54%. Detectable antibodies against B.1.351 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 79%, Day 209 58%. Detectable antibodies against B.1.351 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 63%, Day 43 100%, Day 119 71%, Day 209 79%. Decreased neutralization on some assays was seen especially in those vaccinees tested that were 71+." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~10-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~3 fold without the deletion] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were significant, but ~500x weaker than in previously infected patients after first dose." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A two-dose regimen of (AstraZeneca) ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, vaccine efficacy against severe Covid-19 is undetermined." "" "" "" "Madhi" "2021" "https://doi.org/10.1101/2021.02.10.21251247" "doi:10.1101/2021.02.10.21251247" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "humoral response durability" "" "" "In a prospective study of 107 hospitalized patients, decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7 and P.1 variants for at least 6 months (last of two samples taken) in patients previously hospitalized for COVID-19. A weaker protection was however observed for the B.1.351 variant." "" "" "" "Betton" "2020" "https://doi.org/10.1093/cid/ciab308" "doi:10.1093/cid/ciab308" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Beta (B.1.351) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination." "" "" "" "" "" "nan" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 34 convalescent cases 4–9 weeks following infection in June 2020, before the emergence of B.1.1.7, neutralization titers against B.1.351 were, on average, 13.3-fold reduced compared with an early Victoria sample (p < 0.0001). Significantly, 18 of 34 samples failed to reach 50% neutralization at a plasma dilution of 1:20, with a number showing a near total reduction of neutralization activity. In 13 convalescent cases 4–9 weeks following infection with B.1.1.7, neutralization titers against B.1.351 were, on average, 3.1-fold reduced compared with an early Victoria sample (p < 0.0001)." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Beta (B.1.351) variant is 0.4x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Unlike wild type or B.1.1.7, B.1.351 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. PG: The virus used in these expriments has a non-typical deletion+sub in the 242 region." "" "" "" "Montagutelli" "2021" "https://doi.org/10.1101/2021.03.18.436013" "doi:10.1101/2021.03.18.436013" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v3 reduced 8.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The B.1.351 variant constellation causes an ∼20-fold increase in affinity for ACE2 compared with Wuhan RBD, which may influence transmissibility." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x cleavage of S2 relative to WA1 (D614G) wildtype by Beta variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but A701V is downstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Beta (B.1.351) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine plasma neutralization of B.1.351-spike virus was nominally robust but lower (~3x) than other variants of concern." "" "" "" "Liu" "2021" "https://doi.org/10.1056/NEJMc2102017" "doi:10.1056/NEJMc2102017" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Testing against B.1.351 the 20 most effective mAbs (19 anti-RBD, 1 anti-NTD) from a screen of 377 against wild type, 4 of 20 antibodies had >10-fold fall in neutralization titers, with most of these showing a complete knockout of activity. This is in line with the key roles of K417, E484, and N501, in particular E484, in antibody recognition of the ACE2 interaction surface of the RBD. Regeneron mAb cocktail: The neutralization of REGN10987 was unaffected by B.1.351, while REGN10933 was severely impaired (773-fold). AstraZeneca mAb cocktail: Neutralization by the AZ pair of antibodies was little affected on B.1.351 compared with Victoria." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Beta Molnupiravir (MK-4482) had ~1.75x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v1 virus has reduced neutralization activity vs wild type: 34.5x (30 sera Pfizer median 9 days post 2nd dose) and 27.7x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.351 defining mutations: Significant shift to infection in those without pre-existing conditions (79.6% vs 89% for non-VOC cases). Significant increase in hospitalization rate (19.3% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.3% vs 0.6% for non-VOC cases). PG: seems to be different notations around the LAL deletion, using the minimal shared definition to catch as many as possible." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Beta (B.1.351) has an IC50 fold change of 0.88x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Compared to Alpha (B.1.1.7) variant, odds of progressing to severe disease were 1.24-fold (95% CI: 1.11-1.39) higher for Beta. Odds of progressing to critical disease were 1.49-fold (95% CI: 1.13-1.97) higher. Odds of COVID-19 death were 1.57-fold (95% CI: 1.03-2.43) higher." "" "" "" "Abu-Raddad" "2021" "https://doi.org/10.1101/2021.08.02.21261465" "doi:10.1101/2021.08.02.21261465" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Beta (B.1.351) has an IC50 fold change of 0.15x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using B.1.351 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~3-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~10 fold with L242del] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were signficiant, but >100x weaker than in previously infected patients after first dose." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, one third (5/15) of sera neutralized this B.1.351 pseudotype and only three had ID50 titers above 100. Only two of the 15 sera achieved 80% neutralization." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Inoculation with the B.1.351 isolate resulted in lower clinical scores in 6 rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. Our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity." "" "" "" "Munster" "2021" "https://doi.org/10.1101/2021.05.07.443115" "doi:10.1101/2021.05.07.443115" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission." "" "" "" "Yinda" "2021" "https://doi.org/10.1101/2021.05.05.442780" "doi:10.1101/2021.05.05.442780" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "4 health care workers in the 20's and 30's with no underlying conditions and seropositivity or confirmed 2020 SARS-CoV-2 infections were confirmed to have B.1.351 infection during a Februrary 2021 hospital outbreak in Luxembourg. Symptoms were mostly mild on first infection, and milder on second infection." "" "" "" "Staub" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.18.2100423" "doi:10.2807/1560-7917.ES.2021.26.18.2100423" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "During an outbreak of SARS-CoV-2 501Y.V2 in a nursing home, all non-vaccinated residents (5/5) versus half of those fully vaccinated 2-5 weeks prior with BNT162b2 (13/26) were infected. Two of 13 vaccinated versus 4 of 5 non-vaccinated residents presented severe disease. BNT162b2 did not prevent the outbreak, but reduced transmission and disease severity. Among the 13 fully vaccinated residents who were infected, 2 (15.4%) presented with an asymptomatic disease, 9 (69.2%) developed mild to moderate symptoms, and 2 (15.4%) progressed to severe disease with fatal evolution secondary to acute respiratory distress syndrome (ARDS). There was no relationship between anti-S antibody levels at diagnosis and disease severity. Overall, the proportion of residents with severe disease in the non-vaccinated group (4/5) was higher than that in the vaccinated group (2/13). Only 1 vaccinated staff, but 10 unvaccinated were infected in the outbreak (no severe disease)." "" "" "" "Bailly" "2021" "https://doi.org/10.1093/cid/ciab446" "doi:10.1093/cid/ciab446" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v3 virus has reduced neutralization activity vs wild type: 42.4x (30 sera Pfizer median 9 days post 2nd dose) and 19.2x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.351 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. B.1.1.351 variant constellation ablates Class 3 N-terminal domain targeting antibodies COV2-2489 and COV2-2676 (the only two tested)." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.351 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0020 for moderate resistance." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.351 in 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In a Syrian hamster model, B.1.351 variant virus had >4x reduction in YRNT90 (measure of neutralization) using wild type convalescent sera. PG: Note that exact sequence for B.1.351 used was not disclosed." "" "" "" "Cochin" "2021" "https://doi.org/10.1101/2021.04.19.440435" "doi:10.1101/2021.04.19.440435" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer" "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.351 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the B.1.351 variants used, using the most popular as a stad in]" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "VSV pseudotype B.1.351 showed 7.86-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections)." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.351 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine elicited antibodies neutralized virus with the B.1.351 spike protein had an average 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abrogates Bamlanivimab, Etesevimab, or their combined use neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In one of eight cell lines tested (293T lung cells), a modest increase in cell entry was observed." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype B.1.351 showed slight decrease in cell entry relative to wild type in 263T-ACE2 (kidney) cell line, and slight increase in Calu-3 (lung). Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "VSV pseudotype B.1.351 entry mediated by the S proteins of the B.1.351 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.351 lineage effectiveness was observed as 16.9% (95% CI [10.4,23.0]) against infection, and 0% against severe/critical/fatal disease (95% CI [0-19.0]). Two weeks or more after 2nd dose, effectiveness climbed to 75.0% [70.5,78.9] against infection, and 100% against severe/critical/fatal disease (95% CI [73.7,100])." "" "" "" "" "" "," "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "," "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Approximately 6-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846" "T95I" "NC_045512.2:g.284C>T" "YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "65yo female with no severe Covid-19 risk factors tested positive 36 days after second dose of BNT162b2 (Pfizer) vaccine. Presented with fatigue, sinus congestion, and a headache developed; her symptoms plateaued and began to resolve six days later. [Mising genome coverage in regions of Spike covering clinically relevant mutations K417T, L452R, E484K, A701V, D796H, N501Y]" "" "" "" "Hacisuleyman" "2021" "https://doi.org/10.1056/NEJMoa2105000" "doi:10.1056/NEJMoa2105000" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 ('Kappa') reduced 3.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22317,22319,22320,23399,23401,23402,23403" "T95I,D253G,D253G,D253G,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "B.1.526 (Iota) substantially increased IFR in older adults: by 46% (95% CI: 7.4 – 84%) among 45-64 year-olds, 82% (95% CI: 20 – 140%) among 65-74 year-olds, and 62% (95% CI: 45 – 80%) among 75+ during Nov 2020 – Apr 2021, compared to baseline IFR estimated for preexisting variants. [minimum clade defining mutations listed]" "" "" "" "Yang" "2021" "https://doi.org/10.1101/2021.08.04.21261596" "doi:10.1101/2021.08.04.21261596" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from vaccinees [ChAdOx1 and BNT162b2 primarily used in UK] shows decreased ability to neutralize B.1.621 compared to first wave virus and Alpha, with a magnitude of change similar to Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against B.1.621." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Sera from individuals who have been infected with Delta does not have strong neutralising activity against B.1.621" "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 69 test-positive were Mu. Two dose vaccine efficacy against Mu was 90.4% (73.9-96.5%), one dose VE was 45.8% (0.0-88.9%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using live B.1.621 virus and a cytopathic effect-based assay, sera from 37 Pfizer/BioNTech BNT162b2 vaccinees collected 10-20 days post-booster showed significantly lower (95) but still 'robust' neutralization than against ancestral B.1 virus (107)." "" "" "" "Messali" "2021" "https://doi.org/10.1002/jmv.27247" "doi:10.1002/jmv.27247" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 7.6x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. [This is a greater reduction than Beta @ 6.3x]" "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 12.4x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. [This is a greater reduction than Beta @ 8.2x]" "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403" "T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 1.5x-fold lower (95% CI: 0.05x-0.07x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403" "T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 4.4-fold lower (95% CI: 4.3x-4.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,23012,23271,23399,23401,23402,23403,23604,23948" "T95I,E484K,A570D,D614G,D614G,D614G,D614G,P681H,D796H" "NC_045512.2:g.284C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2386G>C" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp796His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "51yo female with no severe COVID-19 risk factors tested positive 19 days after second dose of mRNA-1273 (Moderna) vaccine. Presented with sore throat, congestion, and headache developed; the next day she lost her sense of smell. Symptoms resolved over a one week period. Serum obtained 4 days after symptom onset was tested for neutralization against wild-type virus, the E484K mutant, and the B.1.526 variant. It was equally effective against each. These data suggest that the antibody response recognized these variants but was nonetheless insufficient to prevent a breakthrough infection. The virus detected matched neither B.1.1.7 nor B.1.526 VOC strains in wide circulation in New York at the time of infection, though shared some mutations." "" "" "" "Hacisuleyman" "2021" "https://doi.org/10.1056/NEJMoa2105000" "doi:10.1056/NEJMoa2105000" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,23399,23401,23402,23403" "T95I,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21855" "S98F" "NC_045512.2:g.293C>T" "YP_009724390.1:p.Ser98Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly enhanced the transduction rate in raccoon dog (Nyctereutes procyonoides) kidney (62.4%) and Rickett’s big-footed bat (Myotis pilosus) kidney (45.0%) cell cultures compared to epithelial-like human Huh-7 cells (38.9%)." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21929" "A123S" "NC_045512.2:g.367G>T" "YP_009724390.1:p.Ala123Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected in passage with mAb COV2-2489 during alanine mutagenesis antibody mapping experiment." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21969" "C136Y" "NC_045512.2:g.407G>A" "YP_009724390.1:p.Cys136Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massively decreases N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21969" "C136Y" "NC_045512.2:g.407G>A" "YP_009724390.1:p.Cys136Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "These variants dominate in mink infections in North America, sometime supplemented with F486L. The Y453F variant found in other jurisdictions in mink infections is notably absent in North America." "" "" "" "" "2021" "https://doi.org/10.1101/2021.03.18.21253734v3" "doi:10.1101/2021.03.18.21253734v3" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected twice in passage with mAb COV2-2489." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. [PG: This mutation is adjacent to a well known deletion, which may confound the significance of this variant]" "" "" "" "Lucaci" "2021" "https://observablehq.com/@aglucaci/sc2-omicron" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Average 2x neutralization efficiency decrease against sera from 26 Phase II trial Covaxin (BBV152) vaccine recipents. Very similar to B.1.1.7 (~2x) in the same study, and the neutralization from 17 sera of natural infections across B1 lineages." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.04.23.441101" "doi:10.1101/2021.04.23.441101" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~3.5x cleavage of S2 relative to WA1 (D614G) wildtype by Kappa (B.1.617.1) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~4.5x for closely related Delta B.1.617.2 also with P681R at the cleavage site)." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 ('Kappa') reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617.1) showed a 1.79x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cluster of B.1.617[.1] infections related to travel from India to USA, one patient with mild symptoms had received their second dose of Pfizer vaccine more than two weeks before the infection [i.e. vaccine breakthrough]." "" "" "" "Verghese" "2021" "https://doi.org/10.1128/JCM.00741-21" "doi:10.1128/JCM.00741-21" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Kappa (B.1.617.1) shows mean 1.97x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.1) showed a 1.12x increase in binding (KD) relative to D614G, but described as 'not significant'. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Kappa (B.1.617.1) shows 5.71x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617.1) showed a 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Kappa (B.1.617.1) has an IC50 fold change of 80.2x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Kappa (B.1.617.1) has an IC50 fold change of 0.68x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Kappa (B.1.617.1) has an IC50 fold change of 2.3x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Kappa (B.1.617.1) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Omicron BA.2 has an IC50 fold change of 0.09x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Omicron BA.2 variant is 0.8x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.2 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Omicron BA.2 has an IC50 fold change of 0.08x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.2 has an IC50 fold change of 0.07x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.2 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.2 has an IC50 fold change of 0.04x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21974" "D138Y" "NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.43 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21977" "P139S" "NC_045512.2:g.415C>T" "YP_009724390.1:p.Pro139Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected once in passage with mAb COV2-2676." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990" "Y145del,Y145del" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990" "Y145del,Y145del" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient." "" "" "" "McCarthy" "2021" "https://doi.org/10.1126/science.abf6950" "doi:10.1126/science.abf6950" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990,21993,21995,23012,23399,23401,23402,23403" "Y145del,Y145del,H146del,H146del,E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.436_438del,NC_045512.2:g.436_438del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.His146del,YP_009724390.1:p.His146del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Normalized for particle number, on ACE2.293T cells showed that the B.1.618 spike protein was about as infective as D614G wild type." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21993,21995" "H146del,H146del" "NC_045512.2:g.436_438del,NC_045512.2:g.436_438del" "YP_009724390.1:p.His146del,YP_009724390.1:p.His146del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient." "" "" "" "McCarthy" "2021" "https://doi.org/10.1126/science.abf6950" "doi:10.1126/science.abf6950" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21997,21998,21999,22000,22001" "K147E,K147E,K147E,K147E,K147E" "NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G" "YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21997,21998,21999,22000,22001" "K147E,K147E,K147E,K147E,K147E" "NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G" "YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21998" "H146Y" "NC_045512.2:g.436C>T" "YP_009724390.1:p.His146Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in 4A8 monoclonal antibody EC50 (i.e. ablated recognition), but much milder effect on mAbs within antigenic supersite 'i'" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22001" "K147Q" "NC_045512.2:g.439A>C" "YP_009724390.1:p.Lys147Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22002" "K147T" "NC_045512.2:g.440A>C" "YP_009724390.1:p.Lys147Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22002" "K147T" "NC_045512.2:g.440A>C" "YP_009724390.1:p.Lys147Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massively decreases N terminal domain antigen recognition by supersite i mAbs S2M28, S2X28, S2X333, 4A8 (but not S2L28)." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22003" "K147N" "NC_045512.2:g.441A>T" "YP_009724390.1:p.Lys147Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22005" "N148S" "NC_045512.2:g.443A>G" "YP_009724390.1:p.Asn148Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong positive selection (up to 72% of supernatant sequences) under six rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22010" "K150E" "NC_045512.2:g.448A>G" "YP_009724390.1:p.Lys150Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22010" "K150E" "NC_045512.2:g.448A>G" "YP_009724390.1:p.Lys150Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong positive selection (up to 40% of supernatant sequences) under three rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22011" "K150T" "NC_045512.2:g.449A>C" "YP_009724390.1:p.Lys150Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 22% of supernatant sequences) after COV47 convalescent plasma assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22011" "K150R" "NC_045512.2:g.449A>G" "YP_009724390.1:p.Lys150Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 18% of supernatant sequences) under two rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22016,22016" "W152R,W152R" "NC_045512.2:g.454T>A,NC_045512.2:g.454T>C" "YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22016,22016" "W152R,W152R" "NC_045512.2:g.454T>A,NC_045512.2:g.454T>C" "YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For NTD-binding neutralizing antibody ADI-56479 this mutation causes a 1000x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22018" "W152C" "NC_045512.2:g.456G>T" "YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The W152C mutation reduced recognition of six NTD neutralizing mAbs, including a complete loss of binding for two of them, with a complementary pattern to that observed for S13I (also found in lineage B.1.427/B.1.429) out of 11 neutralizing mAbs evaluated." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22018" "W152C" "NC_045512.2:g.456G>T" "YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Pseudoviruses carrying the W152C mutation demonstrated small increases in cell entry compared to D614G alone in 293T cells and human airway organoids." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022" "E154K" "NC_045512.2:g.460G>A" "YP_009724390.1:p.Glu154Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pfizer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~3x (compared to ~11x for B.1.351). [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abrogates Bamlanivimab neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Significant decrease in combined Etesevimab+Bamlanivimab neutralization except at the highest concentration measured. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In two of eight cell lines tested (Caco-2 intenstinal and Calu-3 lung), a modest increase in cell entry was observed. This increase was not observed in a Calu-3 cell line with overexpressed ACE2. [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Approximately 2-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22028,22034" "R158G,R158G" "NC_045512.2:g.467_472del,NC_045512.2:g.472A>G" "YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22033,23012,23604" "F157L,E484K,P681R" "NC_045512.2:g.471C>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.23.1-v2 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22033,23604" "F157L,P681R" "NC_045512.2:g.471C>A,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.23.1-v1 reduced 1.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22036" "R158S" "NC_045512.2:g.474A>T" "YP_009724390.1:p.Arg158Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected three times in passage with mAb COV2-2489." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*16:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*07:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DPB1*04:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:03." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type C*07:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22107,22111" "Q183H,Q183H" "NC_045512.2:g.549G>T,NC_045512.2:g.549G>T" "YP_009724390.1:p.Gln183His,YP_009724390.1:p.Gln183His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome" "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132" "R190S" "NC_045512.2:g.570G>T" "YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.69 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604" "R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in B.1.640.2 variant was ~1000x folds more significant in 8 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604" "R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1.640.2 variant was ~5.6x folds more significant in 9 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22188,23399,23401,23402,23403" "I210del,D614G,D614G,D614G,D614G" "NC_045512.2:g.629_631del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "A 42yo Iranian male was reinfected with B.1.36 lineage virus 128 days after infection with genetically distinct B.1.36 virus, with negative PCR tests in between. In the first instance patient presented with cough, headache, severe diarrhea. In the second instance symptoms were more severe: body pain, shortness of breath, headache and anosmia. Anti-SARS-CoV-2 IgG and IgM tests were negative after both episodes. [Non-seroconversion may be associated with elevated risk of re-infection] [I210del is a homoplasy that has appeared in several disparate parts of the global phylogenetic tree, including A and B lineages, primarily in LMICs]" "" "" "" "Salehi-Vaziri" "2021" "https://doi.org/10.1016/j.virusres.2021.198421" "doi:10.1016/j.virusres.2021.198421" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.98 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*13:02." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:01." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:02." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227" "A222V,A222V" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite 'i' monoclonal antibodies." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227,23399,23401,23402,23403" "A222V,A222V,D614G,D614G,D614G,D614G" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3). Both cases were mild. Second case also includes N:p.A220V" "" "" "" "Brehm" "2021" "https://doi.org/10.3390/v13040661" "doi:10.3390/v13040661" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227,23399,23401,23402,23403" "A222V,A222V,D614G,D614G,D614G,D614G" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "humoral response durability" "" "" "27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3), i.e. with a 9 month interval. Both cases were mild. No significant differences in the neutralizing capacity of the two lineages were observed in 4 sera taken (1 pre-reinfection, three post-reinfection). Neutralizing antibody titres (IC50) before and immediately after re-infection were <300 against both strains, and jumped >7x upon re-infection. Viral titres were also higher in the second case. Second case also includes N:p.A220V" "" "" "" "Brehm" "2021" "https://doi.org/10.3390/v13040661" "doi:10.3390/v13040661" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22293" "L244S" "NC_045512.2:g.731T>C" "YP_009724390.1:p.Leu244Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22301" "S247R" "NC_045512.2:g.739A>C" "YP_009724390.1:p.Ser247Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22304" "Y248H" "NC_045512.2:g.742T>C" "YP_009724390.1:p.Tyr248His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22314" "P251L" "NC_045512.2:g.752C>T" "YP_009724390.1:p.Pro251Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317" "G252D" "NC_045512.2:g.755G>A" "YP_009724390.1:p.Gly252Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317,22319,22320" "D253G,D253G,D253G" "NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317,22319,22320" "D253G,D253G,D253G" "NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite 'i', but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22319" "D253Y" "NC_045512.2:g.757G>T" "YP_009724390.1:p.Asp253Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite 'i', but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22323" "S254F" "NC_045512.2:g.761C>T" "YP_009724390.1:p.Ser254Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite 'i' monoclonal antibodies." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22323" "S254Y" "NC_045512.2:g.761C>A" "YP_009724390.1:p.Ser254Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22326" "S255F" "NC_045512.2:g.764C>T" "YP_009724390.1:p.Ser255Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22328,22329,22331" "G257S,G257S,G257S" "NC_045512.2:g.769G>A,NC_045512.2:g.769G>A,NC_045512.2:g.769G>A" "YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334" "W258R" "NC_045512.2:g.772T>C" "YP_009724390.1:p.Trp258Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334" "W258R" "NC_045512.2:g.772T>C" "YP_009724390.1:p.Trp258Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334,22879,22881,22882,22882,22904,22910,23012" "W258R,N440K,N440K,N440K,N440K,N450D,N450D,E484K" "NC_045512.2:g.772T>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22340" "A260T" "NC_045512.2:g.778G>A" "YP_009724390.1:p.Ala260Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22344" "G261D" "NC_045512.2:g.782G>A" "YP_009724390.1:p.Gly261Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Multiple mink but no humans on one farm in Denmark, potential adaptation." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22377" "P272L" "NC_045512.2:g.815C>T" "YP_009724390.1:p.Pro272Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*02:01." "" "" "" "Dolton" "2021" "https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf" "doi:10.1101/2021.06.21.21259010v2.full.pdf" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22377" "P272L" "NC_045512.2:g.815C>T" "YP_009724390.1:p.Pro272Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*08:01." "" "" "" "Dolton" "2021" "https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf" "doi:10.1101/2021.06.21.21259010v2.full.pdf" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 1.2x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.3 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22583" "V341I" "NC_045512.2:g.1021G>A" "YP_009724390.1:p.Val341Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22599" "R346T,R346T,R346T,R346T" "NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22599" "R346T,R346T,R346T,R346T" "NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22599,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22939,22942,22942,22992,23009,23010,23012,23013,23027,23029,23030,23031,23053,23054,23055,22992,22995,23060,23061,23062,23063,23071,23074,23075" "R346T,R346T,R346T,R346T,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N460K,N460K,N460K,S477N,E484A,E484A,E484A,E484A,F490S,F490S,F490S,F490S,Q498R,Q498R,Q498R,T478K,T478K,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H" "NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The hACE2-binding affinity of XBB.1.5 RBD has a dissociation constant KD of 3.4 nM, where S486P is the distinguishing Spike mutation vs parent XBB.1 RBD with a much weaker KD (19 nM), as measured by surface plasmon resonance (SPR) assays." "" "" "" "Yue" "2023" "https://doi.org/10.1101/2023.01.03.522427" "doi:10.1101/2023.01.03.522427" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346K,R346K" "NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 53% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346K,R346K" "NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation, which has emerged in some Omicron sequences, has a 0.7x reduction in neutralization activity with Sotrovimab in a VSV model on Vero E6 cells. [Omicron sequences with R346K may very well have a non-additive neutralization rather than 2.7x+0.7x = 3.4x]" "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346K,R346K" "NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346I,R346I" "NC_045512.2:g.1037G>T,NC_045512.2:g.1037G>T" "YP_009724390.1:p.Arg346Ile,YP_009724390.1:p.Arg346Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Provides ~80% escape from mAb COV2-2130, even though its appearance in culture is formed without selective mAb pressure." "" "" "" "Dong" "2021" "https://doi.org/10.1101/2021.01.27.428529" "doi:10.1101/2021.01.27.428529" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 2/3 antibody C603." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 30% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22622" "N354D" "NC_045512.2:g.1060A>G" "YP_009724390.1:p.Asn354Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.13 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22624" "N354K" "NC_045512.2:g.1062C>A" "YP_009724390.1:p.Asn354Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22627,22629" "K356T,K356T" "NC_045512.2:g.1067A>C,NC_045512.2:g.1067A>C" "YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.14 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22629" "K356R" "NC_045512.2:g.1067A>G" "YP_009724390.1:p.Lys356Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22632" "R357K" "NC_045512.2:g.1070G>A" "YP_009724390.1:p.Arg357Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.18 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.72 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as 'stabilizing' since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22661" "V367I" "NC_045512.2:g.1099G>A" "YP_009724390.1:p.Val367Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22679" "S373P" "NC_045512.2:g.1117T>C" "YP_009724390.1:p.Ser373Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Reduce affinity for mildly cross-reactive CR3022 (2003 pandemic SARS monoclonal antibody cross-reactive to SARS-CoV-2)" "" "" "" "Long" "2020" "https://doi.org/10.1128/mBio.02707-20" "doi:10.1128/mBio.02707-20" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22679,23009,23010,23012,23013" "S373P,E484A,E484A,E484A,E484A" "NC_045512.2:g.1117T>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "On December 7, 2021 the estimate of Omicron effective reproduction rate (Rt) is 3.12 [presumably R0 is higher], compared to 1.12 for the dominant Delta VOC at that time. [shorthand of variant list shraed by all contemporary BA lineage used here]" "" "" "" "" "2021" "https://doi.org/10.47326/ocsat.dashboard.2021.1.0" "doi:10.47326/ocsat.dashboard.2021.1.0" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22686" "S375F" "NC_045512.2:g.1124C>T" "YP_009724390.1:p.Ser375Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch." "" "" "" "Lucaci" "2021" "https://observablehq.com/@aglucaci/sc2-omicron" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22696" "K378N" "NC_045512.2:g.1134G>T" "YP_009724390.1:p.Lys378Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for mildly neutralizing COV2-2677 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23402,23403" "P384L,D614G,D614G,D614G,D614G" "NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23402,23403" "P384L,D614G,D614G,D614G,D614G" "NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23402,23403" "P384L,D614G,D614G,D614G,D614G" "NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22745" "V395I" "NC_045512.2:g.1183G>A" "YP_009724390.1:p.Val395Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22766" "I402V" "NC_045512.2:g.1204A>G" "YP_009724390.1:p.Ile402Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22783,22784,22785,22786,22786" "R408S,R408S,R408S,R408S,R408S" "NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C" "YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22783,22784,22785,22786,22786,23009,23010,23012,23013,23060,23061,23062,23063" "R408S,R408S,R408S,R408S,R408S,E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a study of 481 vaccinees going from lowest to highest infection rate, 2 doses of CoronaVac and 1 dose of BNT162b2 had the lowest infection rate at 6.3%, then it was 3 doses of BNT162b2 having a infection rate of 16.6%. 2 and 3 doses of CoronaVac had 48.6% and 20.6% infection rate respectively. 2 doses of BNT162b2 has the highest infection rate at 49.2%." "" "" "" "Zhou" "2022" "https://doi.org/10.1101/2022.05.09.491254" "doi:10.1101/2022.05.09.491254" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 36.9 fold decrease in KD value for antibody binding of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 1.5 fold decrease in KD value of antibody binding of ACE2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection, Two-tailed Wilcoxon matched-pairs signed-rank test shows mild resistance P=0.0361." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs)" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 7.5 fold decrease in KD value for antibody binding of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "1.1 fold drop in IC50 of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.86 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C682, and to a lesser extent C614 and C660" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~6x binding against this isolated mutation. Estesevimab lost ~100x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates binding by RBD-directed mAbs CB6 and 910-30 (targeting the inner side of the RBD). Pseudotyped virus model impairs binding by RBD-directed mAbs 4-20 and REGN10933." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 3-fold decrease in affinity compared to wild-type RBD on the cell surface (Kd = 145.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against IgG1 monoclonal antibody ab1." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The K417N mutation decreased the affinity ~4 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This combination showed ~3x increase binding to ACE2 vs wild type, about half that of the B.1.1.7 lineage, suggesting that the K417N mutation is slightly detrimental to ACE2 binding, probably as a result of disrupting the salt bridge formed with ACE2 residue D30" "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of the B.1.351 RBD variants for ACE2 increased by 3.7 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from B.1.351." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 ('South African') lineage background" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.351 and P.1 samples showed average Ct cycle threshold of 22.2 vs 23 for wildtype (i.e. ~60% higher viral load) comparing 3360 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Moderna vaccinee sera, 2.7x reduction in neutralization, and 6.4 for the full B.1.351 Spike mutation complement, but despite the observed decreases, titers in human vaccinee sera against the B.1.351 variant remained at clinically significant level of ~1/300." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.01.25.427948" "doi:10.1101/2021.01.25.427948" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26)." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.4-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.351 key variants lentivirus. Compare to 8.8-fold reduction against cultured B.1.351 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibodies ab8 and IgG1 ab1. Complete loss for the same antibodies was also observed against S1 pseudotyped and full Spike protein trimers with both B.1.351 and P.1 lineage variants, with slight binding signal for P.1 against IgG1 at the highest concentration tested (1uM). Complete loss of neutralization by these two antibodies was also observed." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "27% of 44 early pandemic exposure convalescent plasma/sera lose all activity against a RBD triple mutant pseudovirus (RBD mutatants of the 501Y.V2 'South African' lineage), while only 23% retained high titres" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure." "" "" "" "Pearson" "2021" "https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) with enrollment June 24 and November 9, 2020 from ~2000 HIV-negative 18-64 year olds (1:1 placebo to treatment), incidence of serious adverse events 14 or more days post- 2nd dose was balanced between the vaccine and placebo groups. A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed 3.5x reduction in neutralization (ID50) for B.1.351 RBD pseudotype HIB-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a similar 3.2x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolished neutralization by mAbs CQ026 and CQ038, greatly diminished neutralization by CQ012 and CQ046." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Average ~10-fold reduction in neutralization efficacy in convalescent sera of 16 health workers infected in Spring 2020." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 2 (B.1.351) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "36,590 variant-specific RT-PCR tests were performed on samples collected between April 12 and May 7, 2021 in France to compare variant spread. Compared to January to March 2021, B.1.351 variant had a significant transmission advantage over B.1.1.7 in some regions (15.1 to 16.1% in Île-de-France and 16.1 to 18.8% in Hauts-de-France). This shift in transmission advantage is consistent with the immune evasion abilities of B.1.351 and the high levels of immunization in these regions." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.05.12.21257130" "doi:10.1101/2021.05.12.21257130" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant of key B.1.351 lineage mutations showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23041,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "100% of the 5 8‑month‑old male R3P1-E4 antibody treated mice suvived 14 days after infection while only 60% the control group mice survived 5 days post infection." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23041,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trachea viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~750x fold drop in the R3P1-E4 antibody in comparison to the IgG control." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23041,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Lung viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~2266x fold drop in the R3P1-E4 antibody in comparison to the IgG control." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (no synergy as level approx. that of N501Y alone)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~5x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied]" "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.64 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 antibody C682" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The K417T mutation decreased the affinity ~2 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~16x binding against this isolated mutation. Estesevimab lost ~16x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 1.1 fold decrease in KD value of antibody binding of ACE2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.25 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 2.9 fold decrease in KD value for antibody binding of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 57.1 fold decrease in KD value for antibody binding of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "2.6 fold increase in IC50 of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,23012,23060,23061,23062,23063" "K417T,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from P.1." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,23012,23060,23061,23062,23063" "K417T,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of the P.1 RBD variants for ACE2 increased by 5.3 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The KD for the pseudotyped P.1-ACE2 interaction is 4.8 nM, showing that binding to P.1 is essentially indistinguishable from B.1.351 (4.0 nM), which binds with ~19x greater affinity that wild type." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22851" "T430I" "NC_045512.2:g.1289C>T" "YP_009724390.1:p.Thr430Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22865" "A435S" "NC_045512.2:g.1303G>T" "YP_009724390.1:p.Ala435Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb H014 (on D614G background)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 3 antibody C669 mildly selected for the emergence of the N440K mutation in vitro (in contrast to N440H which caused mild escape in Class 1/2 mAb C653)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The N440K variant produced ten times higher infectious viral titers than a prevalent A2a strain, and over 1000 folds higher titers than a much less prevalent A3i strain prototype in Caco2 cells. Interestingly, A3i strain showed the highest viral RNA levels, but the lowest infectious titers in the culture supernatants, indicating the absence of correlation between the RNA content and the infectivity of the sample." "" "" "" "Tandel" "2021" "https://doi.org/10.1101/2021.04.30.441434" "doi:10.1101/2021.04.30.441434" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 45% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, eliminated in subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 0.7x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "N501Y substitution decreased the neutralizing and binding activities of CB6 and increased that of BD-23" "" "" "" "Cheng" "2021" "https://doi.org/10.1186/s12985-021-01554-8" "doi:10.1186/s12985-021-01554-8" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882,23399,23401,23402,23403" "N440K,N440K,N440K,N440K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "A 47yo Indian male was reinfected with B.1.36 lineage virus in September 2020 after infection with genetically distinct B.1.36 virus in July, with negative PCR tests in between. While the forst episode was asymptomatic, the second included fever, cough, and malaise. The second case additionally contained stopgain ORF3a:E261*" "" "" "" "Rani" "2021" "https://doi.org/10.1002/jmv.26997" "doi:10.1002/jmv.26997" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444R" "NC_045512.2:g.1331A>G" "YP_009724390.1:p.Lys444Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Identified in 6/20 replicates of recombinant VSV growth in the presence of mAb COV2-2130." "" "" "" "Dong" "2021" "https://doi.org/10.1101/2021.01.27.428529" "doi:10.1101/2021.01.27.428529" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444R" "NC_045512.2:g.1331A>G" "YP_009724390.1:p.Lys444Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 20% of supernatant sequences) under two rounds of COV-NY convalescent plasma passage, eliminated in rounds three and four" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444T" "NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444T" "NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444T" "NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Results in 3.7-fold drop in neutralization potency for COVA2-29, which is a cluster I RBD141 specific antibody." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 14% of supernatant sequences) after COV-NY convalescent plasma assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-01 and moderately resistant to 2H04 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolishes binding efficiency vs wild type for mAb REGN10933." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Improvement in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22896" "V445A" "NC_045512.2:g.1334T>C" "YP_009724390.1:p.Val445Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 41% appearance in 2 passages against Regeneron monoclonal antibody RGN10987 @ 10ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Decrease in neutralization capability of all 4 convalescent sera tested (1 ablated)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 1 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-02, SARS2-32 and SARS2-35 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2499 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed a ~4x drop in sensitivity." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 95% appearance in 2 passages against Regeneron monoclonal antibody RGN10934 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-07 nd moderately resistant to SARS2-16 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 4 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Most effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations), triple replicates. Against a broader panel of 16 convalescent plasma (no replicates), reductions in neutralization are considerably less dramatic in pattern, and sometime neutralization increases." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910,23012,23039,23040,23373,25046" "N450D,N450D,E484K,Q493R,Q493R,T604I,P1162S" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1811C>T,NC_045512.2:g.3484C>T" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Thr604Ile,YP_009724390.1:p.Pro1162Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22905" "N448S" "NC_045512.2:g.1343A>G" "YP_009724390.1:p.Asn448Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22907" "Y449N" "NC_045512.2:g.1345T>A" "YP_009724390.1:p.Tyr449Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22907" "Y449H" "NC_045512.2:g.1345T>C" "YP_009724390.1:p.Tyr449His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912,22916" "L452M,L452M" "NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A" "YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912,22916" "L452M,L452M" "NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A" "YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-02 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We observed increased entry by pseudoviruses carrying the L452R mutation compared to D614G alone, with a 6.7 to 22.5-fold increase in 293T cells and a 5.8 to 14.7-fold increase in human airway organoids." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.32 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~1.7-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Increased stability of RBD expression in yeast, suggesting increased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. L452R conferred about a two-fold reduction in neutralisation by vaccine sera, but was not statistically significant with this sample size." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "L452R derivative virus did not induce IFN-gamma expression even at the highest concentration tested (10 nM) in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456)." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs X593 and P2B-2F6" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. [listed as L454R in Figure, but L452R in text, also text suggests not statistically significant, but error bars say otherwise in Figure 4]" "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "10 of 14 RBD-specific mAbs that showed at least 10-fold reduced neutralization of B.1.427/B.1.429 variant pseudotype (S13I, W152C, and L452R) were also found to poorly bind to just a L452R RBD mutant, demonstrating a role for this mutation as an escape mechanism for certain RBD-targeting mAbs." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02." "" "" "" "Motozono" "2021" "https://doi.org/10.1016/j.chom.2021.06.006" "doi:10.1016/j.chom.2021.06.006" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2/3 antibody C628 and class 2 antibody C643 selected for the emergence of the L452R mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.67 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Ablation of neutralization capability of 3 of 4 convalescent sera tested, the other is significantly hindered." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Observed ~2x decrease on average in neutralization efficacy in convalescent sera of 16 health workers." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 3 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~5x binding against this isolated mutation. Cligavimab lost ~4x binding against this isolated mutation. Regdanvimab lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012" "L452R,L452R,L452R,E484Q" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484Q had a ~5x drop in neutralization (vs ~10x for E484K). When E484Q and L452R were combined, the fold change was significant, but similar to that of L452R alone (~2x), suggesting no evidence for an additive effect [perhaps even E484Q effect dilution]." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012" "L452R,L452R,L452R,E484K" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant combination shows a ~4-5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, same as L452R alone." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x infectivity advantage to the spike particles [less than L452R or E484Q alone working with the delins]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The combination caused a 3-fold increase in infectivity relative to D614G wild type. [compare to 3.5x for L452R alone]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2.5x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617) showed a 1.30x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.18x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Pseudotyped viruses for B.1.617 was 2.3-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. [details on the convalescent patient sera collection are not abundantly clear in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x drop in neutralization (NT50) [working with the delins, less than just L452R but more than just E484Q]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617) showed a 1.85x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617) showed a 1.22x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604" "L452R,L452R,L452R,E484Q,P681R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In 9 infected hamsters each for B.1 and B.1.617.1, no significant change in viral load or subgenomic RNA levels were detected." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.05.05.442760" "doi:10.1101/2021.05.05.442760" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604" "L452R,L452R,L452R,E484K,P681R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant combination shows a ~3x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, significantly less of a decrease than any B.1.617 lineage variants alone, suggesting a synergistic effect on cell entry while maintaining known immunity esacpe mutants." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604" "L452R,L452R,L452R,E484Q,P681R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Gross examination of 3+3 hamster lung specimens showed pronounced congestion and hemorrhages on days 5 and 7 post-infection in the case of the B.1.617.1 as compared with the B.1. The lung lesions with the B.1 variant were minimal to mild whereas with B.1.617.1 they were moderate. For B.1 pneumonic changes were minimal to mild (inflammatory cell infiltration, focal consolidation and mild congestion). The pronounced changes (moderate to severe) with mononuclear infiltration in the alveolar interstitial space, interstitial septal thickening, consolidation and pneumocyte hyperplasia were observed with B.1.617.1 variant consistently." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.05.05.442760" "doi:10.1101/2021.05.05.442760" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,P681R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Normalized for particle number, on ACE2.293T cells showed that the B.1.617 spike protein was >2-fold increase in infectivity relative to D614G wild type." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23060,23061,23062,23063" "L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of these B.1.417/B.1.429 defining variants in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 583 test-positive were Epsilon. Two dose vaccine efficacy against Epsilon was 97.6 (90.2-99.4%), one dose VE was 76.3 (48.1-89.1%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 7.42x drop in neutralization (NT50) [mostly from 3 of the sera]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The L452R mutation increased the infectivity more than two-fold in these conditions." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this RBD mutation conferred a 2.36x drop in neutralization (NT50)." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~2x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917" "L452Q" "NC_045512.2:g.1355T>A" "YP_009724390.1:p.Leu452Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917" "L452Q" "NC_045512.2:g.1355T>A" "YP_009724390.1:p.Leu452Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.27 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 1.7x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.048x fold change in IC50 in C.37 Lambda" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 3.4x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.038x fold change in IC50 in C.37 Lambda" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.25 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "VSV pseudotyped with Y453F reduced inhibition by most of the 13 potent convalescent serum/plasma samples tested, albeit with variable efficiency (median increase of serum/plasma titer required for 50% neutralization [NT50] = 1.62x, range = 1.02x to 3.43x), indicating that this RBD mutation may compromise SARS-CoV-2 control by preexisting neutralizing antibody responses." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.celrep.2021.109017" "doi:10.1016/j.celrep.2021.109017" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "10-fold reduction in binding efficiency vs wild type for MAb REGN10933." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Casirivimab lost >50x binding against this mutation." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.celrep.2021.109017" "doi:10.1016/j.celrep.2021.109017" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02." "" "" "" "Motozono" "2021" "https://doi.org/10.1016/j.chom.2021.06.006" "doi:10.1016/j.chom.2021.06.006" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "" "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "The induction level of IFN-gamma expression by the Y453F derivative in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456) was significantly lower." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~12x binding against this double mutation. Casirivimab lost ~64x binding against this double mutation. Cligavimab lost ~6x binding against this double mutation. Estesevimab lost ~10x binding against this double mutation. Imdevimab lost ~5x binding against this double mutation. Regdanvimab lost ~8x binding against this double mutation. Sotrovimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed in 4 separate mink farms in Denmark, and Y453F is circulating relatively widely in humans." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920,21762,21763,21764,21765,21766,21766,21761" "Y453F,H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.1358A>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "The so-called 'delta F' variant combination previously observed in mink spillover events also emerged in a lymphoma patient (non-Hodgkin diffuse B-cell lymphoma IV stage B) with a long-term COVID-19 infection (4 months) where 18 de novo mutation occureed overall. Patient was taking rituximab, the B-cell-depleting agent, and had no detectable neutralizing antibody response." "" "" "" "Bazykin" "2021" "https://virological.org/t/emergence-of-y453f-and-69-70hv-mutations-in-a-lymphoma-patient-with-long-term-covid-19/580" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22924,22925,22926" "L455S,L455S,L455S" "NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C" "YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.45 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22926,22927,22927,22928,22930,22930" "F456L,F456L,F456L,F456L,F456L,F456L" "NC_045512.2:g.1366T>C,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>A,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>G,NC_045512.2:g.1368T>A" "YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This double substitution reduces neutralization by RBD-specific mAbs from different clusters, specifically, the cluster I mAb COVA2-29, cluster III mAb COVA2-07 and cluster VI mAb COVA1-12. For COVA1-12 all neutralization activity is abolished, while COVA2-07 activity is just below the level required to calculate an IC50 value." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Moderate in vitro selection against class 1 (Spike 'up' conformation) antibodies C683 and C664. Unclassified antibody C666 selected for the emergence of the F456V mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22936" "K458N" "NC_045512.2:g.1374G>T" "YP_009724390.1:p.Lys458Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.09 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mild escape mutant emergent for class 1 antibody C613 in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460Y" "NC_045512.2:g.1378A>T" "YP_009724390.1:p.Asn460Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22941" "N460I" "NC_045512.2:g.1379A>T" "YP_009724390.1:p.Asn460Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22941" "N460S" "NC_045512.2:g.1379A>G" "YP_009724390.1:p.Asn460Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22964" "I468V" "NC_045512.2:g.1402A>G" "YP_009724390.1:p.Ile468Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22964" "I468V" "NC_045512.2:g.1402A>G" "YP_009724390.1:p.Ile468Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22976" "I472V" "NC_045512.2:g.1414A>G" "YP_009724390.1:p.Ile472Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22976" "I472V" "NC_045512.2:g.1414A>G" "YP_009724390.1:p.Ile472Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb X593 (on D614G background)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~50x binding against this isolated mutation. Estesevimab lost ~8x binding against this isolated mutation. Sotrovimab lost ~30x binding against this isolated mutation. Tixagevimab lost ~15x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some class 1 (Spike 'up' conformation) antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C102, C105 and C144 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 11 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.22 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding, with increasing proportion in subsequent rounds." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility." "" "" "" "Singh" "2021" "https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows some resistence across all antibodies tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of mild positive and negative changes in neutralization capability of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), 10 show low neutralization." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "While S477N itself is highly resistent to a broad range of monoclonal antibodies, combined with S514F high neutralization is restricted to only three antibodies in a broad screen." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-07, SARS2-16 and SARS2-19 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 host variant dependency" "" "" "This mutation's measured interaction affinity with ACE2:p.S19P (0.03% minor allele frequency, found almost exclusively in African/African-Americans in the GnomAD database) was significantly lower than the predicted value, indicating that these mutations were not independent. This is consistent with the fact that the ACE2 residue S19 is adjacent to RBD residue S477 in the contact interface." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-07 and SARS2-16 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 2.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,22995,23042" "T478K,T478K,S494P" "NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1480T>C" "YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Combination of RBD mutations appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome complicated by diffuse alveolar hemorrhage, who was receiving anticoagulation therapy, glucocorticoids, cyclophosphamide, and intermittent rituximab and eculizumab." "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23012" "S477N,E484K" "NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~10x binding against this double mutation. Tixagevimab lost ~16x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was neutralized slightly less than D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Compared to the clade 20A strains that predominated during phase 1 between March and May 2020, the Marseille-4 variant (characterized by this mutation plus N:p.M234I;A376T) was associated with a lower frequency of cough, rhinitis, and olfactory and gustatory disorders. By contrast, hypoxemia was more frequent in patients infected with the Marseille-4 variant." "" "" "" "Fournier" "2021" "https://doi.org/10.1016/j.ijid.2021.03.068" "doi:10.1016/j.ijid.2021.03.068" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "11 cases of re-infection with the 'Marseille-4' variant found within 1028 positive tests, where all of the earlier infections were from different strains. This lineage is also characterized by N:p.M234I;A376T" "" "" "" "Fournier" "2021" "https://doi.org/10.1016/j.ijid.2021.03.068" "doi:10.1016/j.ijid.2021.03.068" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23003" "N481Y" "NC_045512.2:g.1441A>T" "YP_009724390.1:p.Asn481Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Minor variant in initial round of in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009" "V483L" "NC_045512.2:g.1447G>C" "YP_009724390.1:p.Val483Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Remarkably, several of the E484 escape mutants were resistant to neutralization at the highest concentration (1:80 initial dilution) of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), all but one show major resistance." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, 1B07, SARS2-32, SARS2-35 and SARS2-07 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in all 4 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "'E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels'" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 152 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 152 S pseudotype was resistant to neutralization." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This Spike pseudotype for Day 152 virus from a chronically infected patient was completely resistent to REGN10933." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 152 virus from a chronically infected patient: although mAb C1A-B12 had no activity against this pseudotype, all three affinity optimized versions were active; the antibody containing the most mutations, C1A-B12.3, was the most potent (IC50 <0.5 μg/mL)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous." "" "" "" "Braeye" "2022" "https://doi.org/10.1101/2022.05.09.22274623" "doi:10.1101/2022.05.09.22274623" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "3rd exposure to antigen by Delta (B.1.617.2) (n=24) breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a 3rd mRNA vaccine dose in individuals aged 21 –63 years, median age=30 years. Data collected 5.5 months after 2nd vaccination." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In sera from 17 sero-positive blood donors, and 18 months post-infection (May 2020) sera from 17 health care workers in Sweden, a 40x drop in neutralization by Omicron (B.1.1.529) pseudotyped lentivirus was observed in HEK293T cells using the First WHO International Standard (20/136). Median IC50 reduction was ~6x for the blood donors, and ~4.5x for the health care workers." "" "" "" "Sheward" "2021" "https://drive.google.com/file/d/1CuxmNYj5cpIuxWXhjjVmuDqntxXwlfXQ/view" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23071,23074,23075,22992,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,Y505H,Y505H,Y505H,S477N,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1430G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using molecular dynamics simulation, ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations." "" "" "" "Zhang" "2022" "https://doi.org/10.1101/2022.06.05.493249" "doi:10.1101/2022.06.05.493249" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "This mutation occurred in 100% of sequenced virions after 12 passages and led to a 4-fold decrease in convalescent plasma neutralization activity" "" "" "" "Andreano" "2020" "https://doi.org/10.1101/2020.12.28.424451" "doi:10.1101/2020.12.28.424451" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~16x binding against this isolated mutation. Casirivimab lost ~16x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Human sera from 5 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) neutralized this variant 3.4x less relative to reference USA-WA1/2020 strain. 8 convalescent plasma with weak IgG ELISA titre neutralized this variant 2.4x less relative to reference USA-WA1/2020 strain. One plasma failed to neutralize at all. 11 convalescent plasma with moderate IgG ELISA titre neutralized this variant 4.2x less relative to reference USA-WA1/2020 strain. 11 convalescent plasma with high IgG ELISA titre neutralized this variant 2.6x less relative to reference USA-WA1/2020 strain." "" "" "" "Jangra" "2021" "https://doi.org/10.1016/S2666-5247(21" "doi:10.1016/S2666-5247(21" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Analyzing responses to the E484K mutation seen in B.1.351 and P.1 variants, we noted that it did not fall in a region predicted to bind the HLAII alleles tested (table S4). The mutation appeared to have no substantial or differential impact on T cell responses." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484K conferred a ten-fold reduction in neutralisation by vaccine sera." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in all 4 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Monoclonal antibodies 13G9 and 58G6 maintain fairly high neutralization potency, compared to others interfacing with E484K." "" "" "" "Li" "2021" "https://doi.org/10.1101/2021.04.19.440481" "doi:10.1101/2021.04.19.440481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Multiple individuals in two related households were infected with a newly acquired E484K mutation within the B.1.311 lineage. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient's quarantine period." "" "" "" "Sabin" "2021" "https://doi.org/10.1101/2021.10.02.21264415" "doi:10.1101/2021.10.02.21264415" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2 antibodies C627, C602, C671, C643, and class 2/3 antibody C603 selected for the emergence of the E484K mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a 10x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported moderate increase in affinity compared to wild-type RBD on the cell surface (Kd = 38.5nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "As measured by surface plasmon resonance, RBD with the E484K mutation alone showed a mean 19.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~20x binding against this isolated mutation. Casirivimab lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Of 50 mAbs tested, major loss of neutralization observed for S2N28, S2X615, S2N12, S2X192, S2H7, S2X16, S2X58, S2H70, S2X613, S2D19, S2N22, S2D32, S2H58, S2M11, S2D106, S2X30." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in binding efficiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus)" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed 3.3x reduction in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape due to E484K [given Dec 2020-Apr 2021 time frame of the study, this is assumed to entail both Beta and Gamma lineages]." "" "" "" "Chung" "2021" "https://doi.org/10.1136/bmj.n1943" "doi:10.1136/bmj.n1943" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers of non-human primate sera after one or two doses of Ad26.COV2.S (Jannsen vaccine) against the variants containing the E484K substitution in the RBD were present but reduced (fold reduction between 3.35–7.78, 95% confidence interval all above twofold difference, one-sample t test)." "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "The only mutation in the B.1.351 lineage that appears to contribute to neutralization reduction (~1.7x across 10 convalescent sera from April 2020 infectees)" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.6 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody VH-Fc ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-02, 1B07, SARS2-16, SARS2-32, SARS2-35 and 2B04 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">20% (ELISA significance threshold) drop in antibody binding by this variant against monoclonal antibody VH-Fc ab8." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "E484K pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed a mean 2.8x decrease in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 15/20 convalescent sera was significantly lower against this pseudotyped virus model" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 3 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, E484Q shows a notably resistant profile, comparable to or even more resistant than E484K at later time points (i.e. more resistant to immune cell somatic mutation evolution), see Figure 5a,b. Subject C 32 days post-infection showed >>10 fold reduction in neutralization, reducing to ~10-fold by day 104. Subject B 26 days post-infection showed ~10 fold reduction in neutralization, reducing to ~4x at day 113. Notably, Subject B also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 32, and no E484K immune escape at day 104. Subject I 26 days post-infection showed ~10 fold reduction in neutralization, with no reduction in escape at day 102. Notably, Subject I also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 26, and no E484K immune escape at day 102." "" "" "" "Greaney" "2021" "https://doi.org/10.1016/j.chom.2021.02.003" "doi:10.1016/j.chom.2021.02.003" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Individual variants appearing at <=30% frequency at day 21 in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then appearing all at >95% frequency at day 27." "" "" "" "Chen" "2021" "https://doi.org/10.1101/2021.04.08.21254791" "doi:10.1101/2021.04.08.21254791" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, ELISA tests show 10x reduced efficacy of a majority of isolated antibodies, but only a modest decrease for vaccine plasma overall." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22597,22599" "E484K,R346K,R346K" "NC_045512.2:g.1450G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E484K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22810,22811,22812,22813,22813" "E484K,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~32x binding against this double mutation. COR-101 lost ~160x binding against this double mutation. Casirivimab lost ~16x binding against this double mutation. Estesevimab lost ~32x binding against this double mutation. Regdanvimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~13x more infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22810,22811,22812,22813,22813,23399,23401,23402,23403" "E484K,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Approximately as infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of the individual variants)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23053,23054,23055,23060,23061,23062,23063" "E484K,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Omicron neutralizing antibodies is 0.722x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.5 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.4 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.5 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Omicron Molnupiravir (MK-4482) had no statistically significant change." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Omicron neutralizing antibodies is 0.686x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Values taken 28 days after booster dose was given for BBIBP-CorVvaccine to 390 participants with 130 participants in the 0-14d-10m, 0-21d-10m and 0-28d-10m group. The geometric mean titers (GMT) of neutralizing antibody in 0-28d-10m and 0-21d-10m group were significantly higher than 0-14d-10m group at month 3, month 6 and month 10 after the second dose. A sharply decrease by 4.85-fold (GMT: 94.4-20.3), 4.67-fold (GMT: 134.4-28.8) and 4.49-fold (GMT: 145.5-32.4) was observed from day 28 to month 10 after the second dose in 0-14d-10m, 0-21d-10m and 0-28d-10m group, respectively, and they had similar decline kinetics." "" "" "" "Yao T" "2022" "https://doi.org/10.1101/2022.06.22.22276690" "doi:10.1101/2022.06.22.22276690" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.4 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In the case of VOC B.1.1.7+E484K, the addition of the E484K mutation to N501Y further increased the affinity, to ~15 fold higher than WT RBD (KD ~5 nM), by further increasing the k(on) as measured by surface plasmon resonance. Because the higher k(on) could result in mass transfer limiting binding, we confirmed that the kinetic measurement for this variant was not substantially affected by varying levels of immobilization." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Viral load from lung tissue from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~17.5x folds more significant in 9 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~100x folds more significant in 3 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.025x fold change in IC50 in B.1.1.529 Omicron" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Protection against symptomatic infection caused by Beta/Gamma (assumed by combined presence of N501Y and E484K) was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%)." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)]" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 20 sera from BNT162b2 mRNA vaccine inoculated participants, 6 displayed mild (2x) reductions in neutralization. This variant combination showed the highest reduction, but the magnitude of the differences was small compared to the >4x differences in HA-inhibition titers that have been used to signal potential need for a strain change in influenza vaccines." "" "" "" "Xie" "2021" "https://doi.org/10.1038/s41591-021-01270-4" "doi:10.1038/s41591-021-01270-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.0015x fold change in IC50 in B.1.1.529 Omicron" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Viral load from oral swabs from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied]" "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~12x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of 501 and 484)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~11x, Vero ~10x, and Calu-3 ~11x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.618 was 2.7-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 3-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Pseudotyped viruses for B.1.618 was 2.5-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. [details on the convalescent patient sera collection are not abundantly clear in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The estimated vaccine effectiveness against R.1 strain SARS-CoV-2 infection among residents in a Kentucky skilled nursing facility was 66.2% (95% CI = 40.5%–80.8%) and among health care workers was 75.9% (95% CI = 32.5%–91.4%) in the cohort of only those 14d+ post-vaccination Pfizer booster dose. VE against symptomatic COVID-19 was 86.5% (95% CI = 65.6%–94.7%) among residents and 87.1% (95% CI = 46.4%–96.9%) among HCP. VE against hospitalization was 94.4% (95% CI = 73.9%–98.8%) among residents; no HCP were hospitalized. Three residents died, two of whom were unvaccinated (VE = 94.4%; 95% CI = 44.6%–99.4%)." "" "" "" "Cavanaugh" "2021" "https://doi.org/10.15585/mmwr.mm7017e2" "doi:10.15585/mmwr.mm7017e2" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, RBD-specific mutation E484Q did not significantly confer infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 1.34x drop in neutralization (NT50) [mostly from a single serum]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~4x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the P.1 & P.2 lineages of SARS-CoV-2 in Brazil. The Brazilian arm of the Phase 3 double blind study showed severe/critical disease VE of 81.9% (95% CI: 17.0-98.1), and moderate to severe/critical disease VE of 66.2% (95% CI: 51.0-77.1). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 69.3% of mostly severe infections sequenced as of this report, 69.4% were of P.2 lineage [defining lineage SNPs reported here]." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped P.2 virus has reduced neutralization activity vs wild type: 5.8x (30 sera Pfizer median 9 days post 2nd dose) and 2.9x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs]" "" "" "" "Sapkal" "2021" "https://doi.org/10.1101/2021.04.30.441559" "doi:10.1101/2021.04.30.441559" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed in 4 separate mink farms in Denmark, but not humans, potential adaptation (diff set of farms than N501T)." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutation causes a greater than 100x fold change in IC50 of Ensovibep." "" "" "" "Rothenberger" "2021" "https://doi.org/10.1101/2021.02.03.429164v4" "doi:10.1101/2021.02.03.429164v4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutation causes a greater than 100x fold change in IC50 of Ensovibep." "" "" "" "Rothenberger" "2021" "https://doi.org/10.1101/2021.02.03.429164v4" "doi:10.1101/2021.02.03.429164v4" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 5 antibodies." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">60% drop in antibody binding (ELISA) by this variant against monoclonal antibody VH-Fc ab8." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed striking resistance with only 38% neutralization at the highest concentration tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 1 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.13 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "IC50 relative to wildtype drops ~8x in neutralization efficiency between 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-07, SARS2-19, 1B07, SARS2-16 and 2B04 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Modest decrease in in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23023" "N487K" "NC_045512.2:g.1461T>G" "YP_009724390.1:p.Asn487Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, high ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.11 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Based on structural modelling, this change detected on day 128 sequencing in a chronically infected patient would alter an extensive network of polar interactions with antibody residue R94VH, a germline antibody residue that is conserved in all of the potent VH3-53/3-66-derived antibodies isolated from a convalescent donor 5 weeks after infection." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-32." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (3 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2/3 mAb C603 modestly selected for the emergence of this mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 3 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23063" "Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This Spike pseudotype for Day 146 virus from a chronically infected patient was completely resistent to REGN10933. The variant had a 4-fold decrease in REGN10987 neutralization sensitivity (2nd component of the Regeneron mAb cocktail)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23063" "Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 146 virus from a chronically infected patient: resistant to neutralization by mAb C1A-B12, and was still resistant to the affinity enhanced antibodies derived from it (i.e. no affinity maturation effect on neutralization)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23063" "Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 146 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 146 S pseudotype was resistant to neutralization." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) resistant to 3 individual sera at >4x" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 23% of supernatant sequences) after C121 monoclonal antibody assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs X593, 261-262, H4, and P2B-2F6" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490V" "NC_045512.2:g.1468T>G" "YP_009724390.1:p.Phe490Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Dominant (70%) in day 21 of prolonged infection in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then nearly disappearing (<5%) by day 27." "" "" "" "Chen" "2021" "https://doi.org/10.1101/2021.04.08.21254791" "doi:10.1101/2021.04.08.21254791" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2 mAb C627 modestly selected for the emergence of this mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in binding efficiency vs wild type for mAbs CB6/LY-CoV16 and LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 2 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, S484P shows a slightly resistant profile across both timepoints (i.e. resistant to immune cell somatic mutation evolution)" "" "" "" "Greaney" "2021" "https://doi.org/10.1016/j.chom.2021.02.003" "doi:10.1016/j.chom.2021.02.003" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using molecular dynamic simulation, the mildly (~1kcal/mol) enhanced binding energy of this variant is primarily contributed by Tyr505 (−4.98 kcal/mol) which is now involved in a strong hydrogen bonding network with Arg393. Another important energetic contribution comes from the altered orientation of Tyr41 which is now involved with two hydrogen-bonding interactions with Asp355 and Thr500." "" "" "" "" "2021" "https://doi.org/10.1016/j.bbrc.2021.01.035" "doi:10.1016/j.bbrc.2021.01.035" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-01 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Minor variant selected in late rounds of an in vitro evolution experiment for ACE2 binding. Shown to increase the thermostability but decrease the association rate constant of the RBD to ACE2" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Regdanvimab lost ~32x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23048" "G496S" "NC_045512.2:g.1486G>A" "YP_009724390.1:p.Gly496Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23053,23054,23055,23060,23061,23062,23063" "Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. The extent of affinity increase with Q498R and N501Y is not exactly quantified, as E484K always emerged with this duo during in vitro evolution." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Utilizing shark derived vnarbodies, S375F mutation on Omicron RBD disrupts the structure of β-strand, which inhibits binding with 20G6. 20G6 binds to a hidden epitope on RBD which is highly conserved in sarbecoviruses." "" "" "" "Feng" "2022" "https://doi.org/10.1002/smtd.202200387" "doi:10.1002/smtd.202200387" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C663, and to a lesser extent C613." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "Variant within the six key residues in the receptor binding domain (RBD). Independently reported in UK, Australia (same origin as UK), and South Africa (independent origin)." "" "" "" "Flores-Alanis" "2021" "https://doi.org/10.3390/pathogens10020184" "doi:10.3390/pathogens10020184" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome" "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a modest decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In 30 samples collected 111 to 260 days post onset of symptoms, the covalescent plasma can neutralize both the reference USA-WA1/2020 strain and the mouse adapted strain that contains the N501Y spike mutation with similar efficiency." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape by lineage Alpha [defined here as N501Y positive, but E484K negative]." "" "" "" "Chung" "2021" "https://doi.org/10.1136/bmj.n1943" "doi:10.1136/bmj.n1943" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Human sera from 6 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) can neutralize both the reference USA-WA1/2020 strain and the mouse adapted SARS-CoV-2 strain that contains the N501Y spike mutation with similar efficiency." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.69 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x)" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Lowered the neutralization potency of mAb COVA1-12 to the limit of the assay. Decrease in potency was observed against the N501Y pseudotype for the cluster IX mAb COVA2-17." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Vaccinated, but not post-infection sera, show decreased average T cell response to an N501Y peptide. When we primed transgenic mice expressing human HLA-DRB1*0401 with the Wuhan Hu-1 peptide pool, T cell responses to the B.1.1.7 variant peptide pool were significantly reduced (p = 0.0286). Furthermore, the T cell response to the spike N501Y mutation common to all three of the current VOC was ablated." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~8x binding against this isolated mutation. Regdanvimab lost ~6x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.2x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 and day 14 post-2nd dose) against a recombinant single variant virus (modified replicating WA-1 cDNA clone) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation alone accounts for most of the increased infectivity of the Alpha variant, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters, and Vero E6 (NHP) and Calu-3 (human) cell lines." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.03.08.434499" "doi:10.1101/2021.03.08.434499" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Contrary to other reports on N501Y containing lineages (i.e. with additional mutations), N501Y alone may have an even greater affinity for a human monoclonal antibody specific for wild type. These results suggest that the individual N501Y mutation does not contribute to altered viral properties by itself, but may contribute to a collective conformational shift produced by multiple mutations." "" "" "" "Klegerman" "2021" "https://doi.org/10.1101/2021.04.26.441517" "doi:10.1101/2021.04.26.441517" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "As measured by surface plasmon resonance, RBD with the N501Y mutation alone showed a mean 2.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "0.7x reduction in neutralization by key variant in several variants of concern in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In silico methods (PyMOL and PDBePISA) involving mutagenesis (N501Y mutation) and interface analysis focusing on the Spike RDB-ACE2 interaction showed that the SARS-CoV-2 N501Y mutant (lineage B.1.1.7) establishes a more significant number of interactions relating to the mutant residue Y501 (Spike RDB) with residues Y41 and K353 (ACE2). This finding shows that the increased infectivity of SARS-CoV-2 lineage B.1.1.7 is associated with the interaction force between the Spike RBD Y501 mutant residue with the ACE2 receptor, which in this strain is increased." "" "" "" "" "2021" "https://doi.org/10.1101/2020.12.29.424708" "doi:10.1101/2020.12.29.424708" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Of 50 mAbs tested, major loss of neutralization observed for S2X128, S2D8, S2X192, S2D19, S2H14, S2H19." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The most frequent RBM mutation N501Y (165,519 instances) makes defective the atypical N-glycosylation sequon NGV 501-503, becoming a key RBM position for the interaction with hACE2-binding hotspot 353." "" "" "" "Gamez" "2021" "https://doi.org/10.1101/2021.04.09.439154" "doi:10.1101/2021.04.09.439154" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slightly increased infection rate amongst the cells. [in what is essentially a replicate experiment in the same paper, because each B.1.351 lineage variant was independetly evaluated and N501 is in both lineages, a significant decrease was observed, therefore the error bars described in this paper should be interpreted carefully]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The N501Y mutation had the biggest effect on ACE2 affinity of any VOC mutation tested, increasing the affinity ~10 fold to KD ~7 nM, by increasing the k(on) ~1.8 fold and decreasing the k(off) by ~ 7 fold as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,22810,22811,22812,22813,22813" "N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~20x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~6x binding against this double mutation. M396 lost ~10x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,22810,22811,22812,22813,22813,23012" "N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In post-vaccination sera from individuals who received one (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) of the BNT162b2 Pfizer vaccine, an average 6.8x reduction in neutralization efficacy of this B.1.351 key variants pseudotype lentivirus vs D614G was observed." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,22810,22811,22812,22813,22813,23012" "N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "~7x reduction in neutralization by key B.1.351 lineage RBD variant combination in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Two of the cohort showed no neutralization against this variant." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23012" "N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~64x binding against this double mutation. COR-101 lost ~50x binding against this double mutation. Casirivimab lost ~250x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~32x binding against this double mutation. Tixagevimab lost ~10x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23271" "N501Y,N501Y,N501Y,N501Y,A570D" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Partial sequencing of S gene reveals two cases of probable early 2021 B.1.1.7 lineage reinfection from non-B.1.1.7 original cases in Lombardy, with 45 to 90 days between infections (less than the typical 90 day guideline for this call). Patients were 56 and 58yo, immunocompenent, with one a former smoker with obesity and dyslipidemia. One case required intubation during first infection, but presented with mild symptoms upon reinfection. The other case convalesced at home during the first episode, but required CPAP support in the subacute clinical unit upon reinfection." "" "" "" "Novazzi" "2021" "https://doi.org/10.1002/jmv.27066" "doi:10.1002/jmv.27066" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~13x, Vero ~10x, and Calu-3 ~10x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~9x, Vero ~8x, and Calu-3 ~8x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed no change in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H ('Ohio') lineage was neutralized similarly to D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells for ACE2 affinity changes vs D614G alone, showing a ~70% drop in IC50 (i.e. increased affinity)." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23521,23522,23524,23525" "N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23071,23074,23075" "Y505H,Y505H,Y505H" "NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed first in a single tiger (cohort of 5), potential adaptation." "" "" "" "McAloose" "2020" "https://doi.org/10.1128/mBio.02220-20" "doi:10.1128/mBio.02220-20" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23071,23074,23075" "Y505H,Y505H,Y505H" "NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23102" "S514T" "NC_045512.2:g.1540T>A" "YP_009724390.1:p.Ser514Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23108" "E516Q" "NC_045512.2:g.1546G>C" "YP_009724390.1:p.Glu516Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23115" "L518Q" "NC_045512.2:g.1553T>A" "YP_009724390.1:p.Leu518Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23120" "A520S" "NC_045512.2:g.1558G>T" "YP_009724390.1:p.Ala520Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "CR3022 (SARS-targeting mAb) cross-reactivity lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23148" "K529T" "NC_045512.2:g.1586A>C" "YP_009724390.1:p.Lys529Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing statistically significant increased infection rate amongst the cells." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant raises PIWAS epitope score from 3.6% to 6.2% (improved immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated that there is very little free energy change (ddG. -0.02 kcal/mol) for this variant (i.e. approx. same stability as wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23373" "T604I" "NC_045512.2:g.1811C>T" "YP_009724390.1:p.Thr604Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped D614G virus has reduced neutralization activity vs wild type: 1.2x (37 sera Pfizer median 9 days post 2nd dose, 37 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.53x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a lentivirus virus pseudotyped with D614G Spike, sera from vaccinated individuals who received the second dose (9–11 days post-second dose of Pfizer) exhibited a robust neutralizing potential, with a mean NT50 value of 99,000. This was an average of a 2-fold increase, relative to sera drawn from the individuals who received one dose of vaccination—mean NT50 dilution of 51,300. Importantly, a 6-fold increase in mean NT50 dilution was obtained when sera from the first vaccination dose was compared to convalescent sera from cohort with severe disease (NT50 51,000 vs 8,700) 21 to 63 days post-onset." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 1.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 2.5 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of 'one-up' trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Negative stain EM shows increased proportion of 'one-up' trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Weissman" "2020" "https://doi.org/10.1101/2020.07.22.20159905" "doi:10.1101/2020.07.22.20159905" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.97x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD mutation conferred a 4.85x drop in neutralization (NT50)." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 conferred a nearly two-fold infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In four cell lines (including 293T-hACE2 cells), this mutation combination increases infectivity vs D614G alone" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.05x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.45x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.35x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to wild type, D614G showed increased infectivity (ie. cold stability) after storage at -20°C for up to 30 days." "" "" "" "Huang" "2021" "https://doi.org/10.1128/msphere.00104-21" "doi:10.1128/msphere.00104-21" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation (a.k.a. 'Doug') outside the receptor binding domain, while highly favorable to improved human-human transmission, decreases transduction in naked mole-rat (Heterocephalus glaber) fibroblast and Japanese pipistrelle bat (Pipistrellus abramus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The increased transduction with Spike D614G ranged from 1.3- to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2 and from 1.5- to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction." "" "" "" "Daniloski" "2021" "https://doi.org/10.7554/eLife.65365" "doi:10.7554/eLife.65365" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Studying 94 COVID-19 extended infection cases with genomics April 1 to October 17, 2020, one case developed 23 mutations in a 19 day period, including this combination in Spike." "" "" "" "Landis" "2021" "https://doi.org/10.1101/2021.05.08.21256775" "doi:10.1101/2021.05.08.21256775" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission." "" "" "" "Plante" "2020" "https://doi.org/10.1038/s41586-020-2895-3" "doi:10.1038/s41586-020-2895-3" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses." "" "" "" "Ozono" "2020" "https://doi.org/10.1038/s41467-021-21118-2" "doi:10.1038/s41467-021-21118-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a slight decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.43x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575" "D614G,D614G,D614G,D614G,L5F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.1x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575" "D614G,D614G,D614G,D614G,L5F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575" "D614G,D614G,D614G,D614G,L5F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.23x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664" "D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.526) showed a 1.78x increase in binding (KD) relative to D614G, even though each variant independently decreases binding." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664" "D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.526) showed a 1.34x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664" "D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.526) showed a 1.02x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600" "D614G,D614G,D614G,D614G,S13I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600" "D614G,D614G,D614G,D614G,S13I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600" "D614G,D614G,D614G,D614G,S13I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.42x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600,22018,22915,22916,22917" "D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. [Stark contrast to 2.15x increase in binding by convalescent plasma 8 months post infection, presumably via memory B cell affinity maturation against L452R effects] 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600,22018,22915,22916,22917" "D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.429 aka Epsilon) showed a 2.82x increase in binding (KD) relative to D614G, indicating a strong marginal effect for L452R." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600,22018,22915,22916,22917" "D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, indicating ablated marginal effect from L452R." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614" "D614G,D614G,D614G,D614G,L18F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.66x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Compare to decreased binding in full Spike variant complements for major lineages containing this variant subset: 0.96x (B.1.351 aka Beta), 0.77x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614" "D614G,D614G,D614G,D614G,L18F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.30x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.28x increase (B.1.351 aka Beta), and 1.14x decrease (P.1 aka Gamma). 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.17x increase (B.1.351 aka Beta), and 1.47x decrease (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614" "D614G,D614G,D614G,D614G,L18F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.07x decrease in binding (KD) relative to D614G. Compare to increased binding in full Spike variant complements for major lineages containing this variant subset: 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing P.1 aka Gamma) showed a 4.24x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing P.1 aka Gamma) showed a 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing P.1 aka Gamma) showed a 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664" "D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing B.1.351 aka Beta) showed a 1.28x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. It shows a 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664" "D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.351 aka Beta) showed a 3.56x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664" "D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing B.1.351 aka Beta) showed a 1.04x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, in contrast to the largely positive binding values for each individual mutation that comprises the set." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21621" "D614G,D614G,D614G,D614G,T20N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.39x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21621" "D614G,D614G,D614G,D614G,T20N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21621" "D614G,D614G,D614G,D614G,T20N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.96x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21638" "D614G,D614G,D614G,D614G,P26S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.23x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21638" "D614G,D614G,D614G,D614G,P26S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.58x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21638" "D614G,D614G,D614G,D614G,P26S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.33x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.51x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing B.1.1.7 aka Alpha) showed no change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.28x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.1.7 aka Alpha) had 5.43x increased binding relative to D614G alone." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing B.1.1.7 aka Alpha) showed a 1.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21801" "D614G,D614G,D614G,D614G,D80A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination showed no change relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21801" "D614G,D614G,D614G,D614G,D80A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.64x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.35x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21801" "D614G,D614G,D614G,D614G,D80A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21846" "D614G,D614G,D614G,D614G,T95I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21846" "D614G,D614G,D614G,D614G,T95I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21846" "D614G,D614G,D614G,D614G,T95I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21974" "D614G,D614G,D614G,D614G,D138Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21974" "D614G,D614G,D614G,D614G,D138Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21974" "D614G,D614G,D614G,D614G,D138Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.32x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22018" "D614G,D614G,D614G,D614G,W152C" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.03x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22018" "D614G,D614G,D614G,D614G,W152C" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.15x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22018" "D614G,D614G,D614G,D614G,W152C" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22132" "D614G,D614G,D614G,D614G,R190S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.59x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22132" "D614G,D614G,D614G,D614G,R190S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22132" "D614G,D614G,D614G,D614G,R190S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.82x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22206" "D614G,D614G,D614G,D614G,D215G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.79x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22206" "D614G,D614G,D614G,D614G,D215G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.19x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22206" "D614G,D614G,D614G,D614G,D215G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D253G,D253G,D253G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.08x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D253G,D253G,D253G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D253G,D253G,D253G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22810,22811,22812,22813,22813" "D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.76x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.75x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22810,22811,22812,22813,22813" "D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22810,22811,22812,22813,22813" "D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22812" "D614G,D614G,D614G,D614G,K417T" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22812" "D614G,D614G,D614G,D614G,K417T" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.28x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22812" "D614G,D614G,D614G,D614G,K417T" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.66x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.05x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.16x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 4.2x-fold lower (95% CI: 0.15x-0.20x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 6.2-fold lower (95% CI: 11.8x-14.3x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 28.7x-fold lower (95% CI: 0.03x-0.05) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "4th antigenic exposure with Omicron (B.1.1.529 [BA.1])(n=29) infection increased variant specific plasma antibody and memory B cell responses as well as overall increased strain specific memory in individuals aged 22 –79 years, median age=33.5 years. Data collected 2.4 months after 3rd vaccination." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 3.4-fold lower (95% CI: 3.2x-3.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "paired testing of vaccine sera against ancestral virus compared to Omicron BA.1 shows that 3-dose vaccine regimen provides over 50x fold increase in protection against Omicron(B.1.1.529 [BA.1]) compared to a 2-dose regimen." "" "" "" "Hao" "2022" "https://doi.org/10.1101/2022.08.12.22278720" "doi:10.1101/2022.08.12.22278720" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 3.9x-fold lower (95% CI: 0.14x-0.17x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 4.5-fold lower (95% CI: 4.3x-4.7x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 78fM for binding to the Omicron BA.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 4.2-fold lower (95% CI: 5.8x-6.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 3.9x-fold lower (95% CI: 0.14x-0.18x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23012" "D614G,D614G,D614G,D614G,E484K" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.42x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23012" "D614G,D614G,D614G,D614G,E484K" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23012" "D614G,D614G,D614G,D614G,E484K" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This variant appears twice in the experiments, with slightly different affinities (both ~1.2x decrease in binding relative to D614G) using flow cytometry and ACE2 ectodomains-Fc portion IgG complex." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23060,23061,23062,23063" "D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23060,23061,23062,23063" "D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23060,23061,23062,23063" "D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.52x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis). Compare to full Spike variant complements for major lineages containing this variant subset: 5.43x (B.1.1.7 aka Alpha), 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23271" "D614G,D614G,D614G,D614G,A570D" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23271" "D614G,D614G,D614G,D614G,A570D" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.18x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23271" "D614G,D614G,D614G,D614G,A570D" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23521,23522,23524,23525" "D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.48x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23521,23522,23524,23525" "D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23521,23522,23524,23525" "D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.21x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant change in virus neutralzation by 18 Pfizer two dose vaccinee sera compared to B.1.1.7. [results without including the used mutation A27S likely generalizable, as this is not a lineage defining mutation]" "" "" "" "Zuckerman" "2021" "https://doi.org/10.1101/2021.03.25.21253908" "doi:10.1101/2021.03.25.21253908" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.26x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23664" "D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23664" "D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23664" "D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed essentially no change in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23709" "D614G,D614G,D614G,D614G,T716I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23709" "D614G,D614G,D614G,D614G,T716I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.58x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23709" "D614G,D614G,D614G,D614G,T716I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.12x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24506" "D614G,D614G,D614G,D614G,S982A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24506" "D614G,D614G,D614G,D614G,S982A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24506" "D614G,D614G,D614G,D614G,S982A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.3x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24642" "D614G,D614G,D614G,D614G,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.56x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24642" "D614G,D614G,D614G,D614G,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.69x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24642" "D614G,D614G,D614G,D614G,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.22x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24914" "D614G,D614G,D614G,D614G,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24914" "D614G,D614G,D614G,D614G,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24914" "D614G,D614G,D614G,D614G,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.96x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23429" "A623T" "NC_045512.2:g.1867G>A" "YP_009724390.1:p.Ala623Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain increases the virus transduction rate in tree shrew (Tupaia belangeri), (as it does in humans) according to pseudotyped VSV experiments." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Six minks were intranasally infected with WA1 isolate, all developed this mutation during infection." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.87 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23587,23587" "Q675H,Q675H" "NC_045512.2:g.2025G>C,NC_045512.2:g.2025G>T" "YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly enhanced the ability of the pseudotyped VSV to infect fat-tailed gerbil (Pachyuromys duprasi) kidney cell cultures, with a transduction rate of 13.4%, close to the 15.7% in epithelial-like human Huh-7 cells while starting from a significantly lower wildtype (Wuhan-Hu-1 Spike VSVdeltaG psuedotype) rate." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 0.9x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681R" "NC_045512.2:g.2042C>G" "YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. [PG: Inferred by conservative AA substitution of described P681H]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681R" "NC_045512.2:g.2042C>G" "YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). [Inference from similar positively charged substitution P681H actually described in the work]" "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing NO statistically significant infection rate change amongst the cells, suggesting that furin cleavage typically used for cell entry is not affected by this change one amino acid upstream of the RXXR recognition pattern." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry)." "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In the absence of N501Y, this Alpha lineage change in the furin clevage site did NOT show significant increase in infectivity relative to wild type, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.03.08.434499" "doi:10.1101/2021.03.08.434499" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic." "" "" "" "Johnson" "2020" "https://doi.org/10.1101/2020.08.26.268854" "doi:10.1101/2020.08.26.268854" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "While the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC)." "" "" "" "Lubinski" "2021" "https://doi.org/10.1101/2021.04.06.438731" "doi:10.1101/2021.04.06.438731" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23399,23401,23402,23403" "P681R,D614G,D614G,D614G,D614G" "NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Quantification of the band intensities showed that the P681R mutation, which lies near the proteolytic processing site, caused a small increase in proteolytic processing as measured by a 2-fold decrease in the ratio of S/S2." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23664" "A701V" "NC_045512.2:g.2102C>T" "YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23664" "A701V" "NC_045512.2:g.2102C>T" "YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.33 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant increases PIWAS epitope score from 0.69% to 2.3% Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed first in a single tiger (cohort of 5), potential adaptation." "" "" "" "McAloose" "2020" "https://doi.org/10.1128/mBio.02220-20" "doi:10.1128/mBio.02220-20" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain showed a decreased capacity to transduce PK-15 (pig kidney, Sus scrofa) and PaKi (black flying fox kidney, Pteropus alecto) cell line cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. T716I was expressed at significantly lower level, accounting for the decreased infectivity of this spike protein. This property may be specific to spike protein biosynthesis in 293T cells and is not likely to reflect the situation in vivo given the reported increase in infectivity of the B.1.1.7 virus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23897" "Q779K" "NC_045512.2:g.2335C>A" "YP_009724390.1:p.Gln779Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 20% appearance in 2 passages against Regeneron monoclonal antibody RGN10989 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23948" "D796H" "NC_045512.2:g.2386G>C" "YP_009724390.1:p.Asp796His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Fatal COVID-19 complications in immunocomprimised patient after immune escape from convalescent plasma" "" "" "" "Kemp" "2020" "https://doi.org/10.1101/2020.12.05.20241927" "doi:10.1101/2020.12.05.20241927" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24000" "S813I" "NC_045512.2:g.2438G>T" "YP_009724390.1:p.Ser813Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb B38" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24077" "D839Y" "NC_045512.2:g.2515G>T" "YP_009724390.1:p.Asp839Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry." "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24077" "D839N" "NC_045512.2:g.2515G>A" "YP_009724390.1:p.Asp839Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry." "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24130" "N856K" "NC_045512.2:g.2568C>A" "YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch." "" "" "" "Lucaci" "2021" "https://observablehq.com/@aglucaci/sc2-omicron" "" "" "" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24170" "I870V" "NC_045512.2:g.2608A>G" "YP_009724390.1:p.Ile870Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Appeared at same time as T478K,S494P but listed separately due to distance and different domains affected in the Spike (i.e. putatively an independent mutation from a functional standpoint since the former are from S1, the latter from S2)." "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24377,24378" "S939F,S939F" "NC_045512.2:g.2816C>T,NC_045512.2:g.2816C>T" "YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (70%) increase in infection rate amongst the cells, hence this individual variant is likely to significantly contribute to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 6/20 convalescent sera was significantly lower against this single variant pseudotyped virus model, showing similar patterns to the pseudotyped virus model of B.1.1.7." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24642" "T1027I" "NC_045512.2:g.3080C>T" "YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 1.51 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Mutation is predicted to lose the T cell epitope for people carrying DRB1*0301 and DRB1*0401, but not for example in those who are DRB1*0701 or DRB1*1501 who would be predicted to show an enhanced response. This is also observed in a study of 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25046" "P1162S" "NC_045512.2:g.3484C>T" "YP_009724390.1:p.Pro1162Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25249,25249,25249" "M1229I,M1229I,M1229I" "NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25350" "P1263L" "NC_045512.2:g.3788C>T" "YP_009724390.1:p.Pro1263Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant in the cytoplasmic tail, shown in vitro to increase Spike subunit fusion required for cell entry" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25855" "D155Y" "NC_045512.2:g.463G>T" "YP_009724391.1:p.Asp155Tyr" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "caveolin binding" "" "" "In silico, this mutation is the only one weakening ORF3a's binding affinity for caveolin-1 (essential for entry and endomembrane trafficking of SARS-CoV-2). This mutation is a widespread homoplasy in 20A and 20B lineages." "" "" "" "Gupta" "2021" "https://doi.org/10.1101/2021.03.26.437194" "doi:10.1101/2021.03.26.437194" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26029" "Q213K" "NC_045512.2:g.637C>A" "YP_009724391.1:p.Gln213Lys" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*01:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26029" "Q213K" "NC_045512.2:g.637C>A" "YP_009724391.1:p.Gln213Lys" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*01:01-restricted CD8+ ORF3a epitope, which is otherwise 'consistently dominant and of high magnitude'." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26256" "F4F" "NC_045512.2:g.12C>T" "YP_009724392.1:p.Phe4Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26268,26269,26270" "T9I,T9I,T9I" "NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T" "YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~300 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26268,26269,26270" "T9I,T9I,T9I" "NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T" "YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26296" "L18I" "NC_045512.2:g.52C>A" "YP_009724392.1:p.Leu18Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (47x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26299" "L19F" "NC_045512.2:g.55C>T" "YP_009724392.1:p.Leu19Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26312" "F23C" "NC_045512.2:g.68T>G" "YP_009724392.1:p.Phe23Cys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~8.8 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26314" "V24M" "NC_045512.2:g.70G>A" "YP_009724392.1:p.Val24Met" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26319" "V25V" "NC_045512.2:g.75A>G" "YP_009724392.1:p.Val25Val" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (45x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26333" "T30I" "NC_045512.2:g.89C>T" "YP_009724392.1:p.Thr30Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26353" "L37F" "NC_045512.2:g.109C>T" "YP_009724392.1:p.Leu37Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26395" "L51I" "NC_045512.2:g.151C>A" "YP_009724392.1:p.Leu51Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (47x overrepresentation vs expected count of ~24 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26416" "V58L" "NC_045512.2:g.172G>C" "YP_009724392.1:p.Val58Leu" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26428" "V62F" "NC_045512.2:g.184G>T" "YP_009724392.1:p.Val62Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (18x overrepresentation vs expected count of ~333 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26442" "N66K" "NC_045512.2:g.198T>G" "YP_009724392.1:p.Asn66Lys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~23 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26447" "S68F" "NC_045512.2:g.203C>T" "YP_009724392.1:p.Ser68Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26447" "S68C" "NC_045512.2:g.203C>G" "YP_009724392.1:p.Ser68Cys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (58x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26456" "P71R" "NC_045512.2:g.212C>G" "YP_009724392.1:p.Pro71Arg" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26467" "V75L" "NC_045512.2:g.223G>C" "YP_009724392.1:p.Val75Leu" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (3762.7x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526" "A2S" "NC_045512.2:g.4G>T" "YP_009724393.1:p.Ala2Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (38x overrepresentation vs expected count of ~334 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526" "A2S" "NC_045512.2:g.4G>T" "YP_009724393.1:p.Ala2Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Emergent as 16% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing." "" "" "" "Avanzato" "2020" "https://doi.org/10.1016/j.cell.2020.10.049" "doi:10.1016/j.cell.2020.10.049" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526,26527,26529" "D3H,D3H,D3H" "NC_045512.2:g.7G>C,NC_045512.2:g.7G>C,NC_045512.2:g.7G>C" "YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (227x overrepresentation vs expected count of ~14 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26528,26528,26528" "A2A,A2A,A2A" "NC_045512.2:g.6A>T,NC_045512.2:g.6A>G,NC_045512.2:g.6A>C" "YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (25x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26530" "D3G" "NC_045512.2:g.8A>G" "YP_009724393.1:p.Asp3Gly" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (31x overrepresentation vs expected count of ~53 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26542" "T7I" "NC_045512.2:g.20C>T" "YP_009724393.1:p.Thr7Ile" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26546" "I8I" "NC_045512.2:g.24T>C" "YP_009724393.1:p.Ile8Ile" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~80 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26573,26576,26577" "Q19E,Q19E,Q19E" "NC_045512.2:g.55C>G,NC_045512.2:g.55C>G,NC_045512.2:g.55C>G" "YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~8 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26620" "C33S" "NC_045512.2:g.98G>C" "YP_009724393.1:p.Cys33Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~32 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26645" "N41N" "NC_045512.2:g.123C>T" "YP_009724393.1:p.Asn41Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (19x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26681" "F53F" "NC_045512.2:g.159C>T" "YP_009724393.1:p.Phe53Phe" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (163x overrepresentation vs expected count of ~567 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26730" "V70L" "NC_045512.2:g.208G>C" "YP_009724393.1:p.Val70Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26748" "I76V" "NC_045512.2:g.226A>G" "YP_009724393.1:p.Ile76Val" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26748" "I76L" "NC_045512.2:g.226A>C" "YP_009724393.1:p.Ile76Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~9 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26749" "I76T" "NC_045512.2:g.227T>C" "YP_009724393.1:p.Ile76Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (19x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26767" "I82T" "NC_045512.2:g.245T>C" "YP_009724393.1:p.Ile82Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "homoplasy" "" "" "This mutation presents mainly within the B.1 (44.0%) and B.1.525 (38.1%) lineages. Currently, 99.7% of the B.1.525 lineage isolates carry the M:I82T mutation. While this mutation is scattered across multiple phylogenetic clades, most cases cluster in two recent clades, suggesting a likely selective advantage in certain haplotype backgrounds." "" "" "" "Shen" "2021" "https://doi.org/10.1080/22221751.2021.1922097" "doi:10.1080/22221751.2021.1922097" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26767" "I82T" "NC_045512.2:g.245T>C" "YP_009724393.1:p.Ile82Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (67x overrepresentation vs expected count of ~42 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26801,26801,26801" "L93L,L93L,L93L" "NC_045512.2:g.279C>G,NC_045512.2:g.279C>A,NC_045512.2:g.279C>T" "YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~628 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26855,26858" "F112F,F112F" "NC_045512.2:g.336C>T,NC_045512.2:g.336C>T" "YP_009724393.1:p.Phe112Phe,YP_009724393.1:p.Phe112Phe" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~463 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26861" "N113N" "NC_045512.2:g.339T>C" "YP_009724393.1:p.Asn113Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (57x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26873" "N117N" "NC_045512.2:g.351C>T" "YP_009724393.1:p.Asn117Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26882,26882" "L120L,L120L" "NC_045512.2:g.360C>A,NC_045512.2:g.360C>T" "YP_009724393.1:p.Leu120Leu,YP_009724393.1:p.Leu120Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26894,26894" "L124L,L124L" "NC_045512.2:g.372C>T,NC_045512.2:g.372C>G" "YP_009724393.1:p.Leu124Leu,YP_009724393.1:p.Leu124Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26895" "H125Y" "NC_045512.2:g.373C>T" "YP_009724393.1:p.His125Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARA_CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26895" "H125Y" "NC_045512.2:g.373C>T" "YP_009724393.1:p.His125Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (22x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26907,26909,26909" "L129L,L129L,L129L" "NC_045512.2:g.385C>T,NC_045512.2:g.387G>A,NC_045512.2:g.387G>T" "YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26927" "E135E" "NC_045512.2:g.405A>G" "YP_009724393.1:p.Glu135Glu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (232x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26951,26951,26951" "V143V,V143V,V143V" "NC_045512.2:g.429G>C,NC_045512.2:g.429G>A,NC_045512.2:g.429G>T" "YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~508 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26966" "H148H" "NC_045512.2:g.444T>C" "YP_009724393.1:p.His148His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26972" "R150R" "NC_045512.2:g.450T>C" "YP_009724393.1:p.Arg150Arg" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~89 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26985" "H155N" "NC_045512.2:g.463C>A" "YP_009724393.1:p.His155Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26987" "H155H" "NC_045512.2:g.465T>C" "YP_009724393.1:p.His155His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27021" "E167Q" "NC_045512.2:g.499G>C" "YP_009724393.1:p.Glu167Gln" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27035,27038" "T172T,T172T" "NC_045512.2:g.516A>G,NC_045512.2:g.516A>G" "YP_009724393.1:p.Thr172Thr,YP_009724393.1:p.Thr172Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27059" "Y179Y" "NC_045512.2:g.537C>T" "YP_009724393.1:p.Tyr179Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27112" "S197T" "NC_045512.2:g.590G>C" "YP_009724393.1:p.Ser197Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (18x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27134" "Y204Y" "NC_045512.2:g.612T>C" "YP_009724393.1:p.Tyr204Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27143" "N207N" "NC_045512.2:g.621C>T" "YP_009724393.1:p.Asn207Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27147" "D209H" "NC_045512.2:g.625G>C" "YP_009724393.1:p.Asp209His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (81x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27367" "Q56X" "NC_045512.2:g.166C>T" "YP_009724394.1:p.Gln56Xaa" "" "open reading frame 6 gene (SARS-CoV-2)" "orf6 gene (SARS-CoV-2)" "open reading frame 6 protein (SARS-CoV-2)" "Orf6 protein (SARS-CoV-2)" "IFN activity" "" "" "The residues listed are determinants of the potent IFN-antagonistic activity of SARS-CoV-2 ORF6 (via blocking mRNA nuclear export)" "" "" "" "Kimura" "2020" "https://doi.org/10.2139/ssrn.3690468" "doi:10.2139/ssrn.3690468" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28144" "L84S" "NC_045512.2:g.251T>C" "YP_009724396.1:p.Leu84Ser" "" "open reading frame 8 gene (SARS-CoV-2)" "orf8 gene (SARS-CoV-2)" "open reading frame 8 protein (SARS-CoV-2)" "Orf8 protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28307,28309,28310,28311" "P13L,P13L,P13L,P13L" "NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T" "YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13)." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28307,28309,28310,28311" "P13L,P13L,P13L,P13L" "NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T" "YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28310" "P13S" "NC_045512.2:g.37C>T" "YP_009724397.2:p.Pro13Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*27:05." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28310" "P13S" "NC_045512.2:g.37C>T" "YP_009724397.2:p.Pro13Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13)." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28769" "T166A" "NC_045512.2:g.496A>G" "YP_009724397.2:p.Thr166Ala" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "Confers a significant PIWAS value decrease (reduced antigenicity)" "" "" "" "Haynes" "2020" "https://doi.org/10.1101/2020.11.23.20235002" "doi:10.1101/2020.11.23.20235002" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28853" "S194T" "NC_045512.2:g.580T>A" "YP_009724397.2:p.Ser194Thr" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28854" "S194L" "NC_045512.2:g.581C>T" "YP_009724397.2:p.Ser194Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In March 2021 this variant had an allele frequency of 47.62 and 7.25% in deceased patients, compared to 35.16 and 3.20% of the same variant in recovered patients, from the Gujarat and global datasets." "" "" "" "Joshi" "2021" "https://doi.org/10.3389/fgene.2021.586569" "doi:10.3389/fgene.2021.586569" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28854" "S194L" "NC_045512.2:g.581C>T" "YP_009724397.2:p.Ser194Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "Mutation with a population frequency of 30% in a Mexican dataset, primarily of lineage 20B, but also present in a substantial number of 20A lineage sequences, suggesting convergent evolution." "" "" "" "Barona-Gomez" "2021" "https://doi.org/10.1101/2021.05.18.21256128" "doi:10.1101/2021.05.18.21256128" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28869" "P199L" "NC_045512.2:g.596C>T" "YP_009724397.2:p.Pro199Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28879" "S202R" "NC_045512.2:g.606T>G" "YP_009724397.2:p.Ser202Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows major increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881" "R203M" "NC_045512.2:g.608G>T" "YP_009724397.2:p.Arg203Met" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows most increase in RNA content of any N mutation tested, suggesting that this mutation improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28977" "S235F" "NC_045512.2:g.704C>T" "YP_009724397.2:p.Ser235Phe" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "Substantially increases epitope and antigen scores in 2 of 579 individuals (should increase immune response). In the B1.1.7 lineage this is largely counteracted by the D3L mutation, which decreases PIWAS signal significantly in 1.5% of COVID patients, for a net neutral effect at the population level." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29239,29239" "M322I,M322I" "NC_045512.2:g.966G>A,NC_045512.2:g.966G>T" "YP_009724397.2:p.Met322Ile,YP_009724397.2:p.Met322Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "Agerer" "2021" "https://doi.org/10.1126/sciimmunol.abg6461" "doi:10.1126/sciimmunol.abg6461" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29247" "T325I" "NC_045512.2:g.974C>T" "YP_009724397.2:p.Thr325Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29247" "T325I" "NC_045512.2:g.974C>T" "YP_009724397.2:p.Thr325Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes partial loss of T cell line responsiveness and CTL killing ability by B*40:01-restricted CD8+ N epitope MEVTPSGTWL 322-331." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29266,29266" "L331F,L331F" "NC_045512.2:g.993G>T,NC_045512.2:g.993G>C" "YP_009724397.2:p.Leu331Phe,YP_009724397.2:p.Leu331Phe" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "Agerer" "2021" "https://doi.org/10.1126/sciimmunol.abg6461" "doi:10.1126/sciimmunol.abg6461" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is 'consistently dominant and of high magnitude'." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is 'consistently dominant and of high magnitude'." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29409" "T379I" "NC_045512.2:g.1136C>T" "YP_009724397.2:p.Thr379Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "335" "R24C" "NC_045512.2:g.70C>T" "YP_009724389.1:p.Arg24Cys" "YP_009724389.1:Arg24Cys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (25x overrepresentation vs expected count of 514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "347" "V28I" "NC_045512.2:g.82G>A" "YP_009724389.1:p.Val28Ile" "YP_009724389.1:Val28Ile" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (30x overrepresentation vs expected count of 143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "383" "S40P" "NC_045512.2:g.118T>C" "YP_009724389.1:p.Ser40Pro" "YP_009724389.1:Ser40Pro" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~58 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "396" "Q44L" "NC_045512.2:g.131A>T" "YP_009724389.1:p.Gln44Leu" "YP_009724389.1:Gln44Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~19 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "443" "V60I" "NC_045512.2:g.178G>A" "YP_009724389.1:p.Val60Ile" "YP_009724389.1:Val60Ile" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "489" "D75G" "NC_045512.2:g.224A>G" "YP_009724389.1:p.Asp75Gly" "YP_009724389.1:Asp75Gly" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "490,490" "D75E,D75E" "NC_045512.2:g.225T>G,NC_045512.2:g.225T>A" "YP_009724389.1:p.Asp75Glu,YP_009724389.1:p.Asp75Glu" "YP_009724389.1:Asp75Glu,YP_009724389.1:Asp75Glu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~20 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Emergent as 22% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing." "" "" "" "Avanzato" "2020" "https://doi.org/10.1016/j.cell.2020.10.049" "doi:10.1016/j.cell.2020.10.049" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 500-523) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-517) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-523) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,509,518" "M85V,M85V,M85V" "NC_045512.2:g.253A>G,NC_045512.2:g.253A>G,NC_045512.2:g.253A>G" "YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val" "YP_009724389.1:Met85Val,YP_009724389.1:Met85Val,YP_009724389.1:Met85Val" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "508" "H81Q" "NC_045512.2:g.243T>A" "YP_009724389.1:p.His81Gln" "YP_009724389.1:His81Gln" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (30x overrepresentation vs expected count of ~20 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "510" "M85K" "NC_045512.2:g.254T>A" "YP_009724389.1:p.Met85Lys" "YP_009724389.1:Met85Lys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~12 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "561" "R99H" "NC_045512.2:g.296G>A" "YP_009724389.1:p.Arg99His" "YP_009724389.1:Arg99His" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "563" "S100C" "NC_045512.2:g.298A>T" "YP_009724389.1:p.Ser100Cys" "YP_009724389.1:Ser100Cys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (33x overrepresentation vs expected count of ~19 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "593" "H110Y" "NC_045512.2:g.328C>T" "YP_009724389.1:p.His110Tyr" "YP_009724389.1:His110Tyr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (22x overrepresentation vs expected count of ~514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "593" "H110D" "NC_045512.2:g.328C>G" "YP_009724389.1:p.His110Asp" "YP_009724389.1:His110Asp" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~11 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "606" "I114T" "NC_045512.2:g.341T>C" "YP_009724389.1:p.Ile114Thr" "YP_009724389.1:Ile114Thr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (155x overrepresentation vs expected count of ~58 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "657" "A131V" "NC_045512.2:g.392C>T" "YP_009724389.1:p.Ala131Val" "YP_009724389.1:Ala131Val" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "677" "A138T" "NC_045512.2:g.412G>A" "YP_009724389.1:p.Ala138Thr" "YP_009724389.1:Ala138Thr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "761" "S166G" "NC_045512.2:g.496A>G" "YP_009724389.1:p.Ser166Gly" "YP_009724389.1:Ser166Gly" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (132x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" +"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "798" "N178S" "NC_045512.2:g.533A>G" "YP_009724389.1:p.Asn178Ser" "YP_009724389.1:Asn178Ser" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" From b0462cd4d70f7db94e9ec71539c32cb3e2ed5dc9 Mon Sep 17 00:00:00 2001 From: Madeline Iseminger <32916719+miseminger@users.noreply.github.com> Date: Tue, 12 Nov 2024 17:45:04 -0800 Subject: [PATCH 093/161] Delete assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v3.0.tsv --- ...kay_functionalAnnotation_SARSCoV2_v3.0.tsv | 1900 ----------------- 1 file changed, 1900 deletions(-) delete mode 100644 assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v3.0.tsv diff --git a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v3.0.tsv b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v3.0.tsv deleted file mode 100644 index 0fa0f393..00000000 --- a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v3.0.tsv +++ /dev/null @@ -1,1900 +0,0 @@ -"organism" "reference accession" "reference database name" "nucleotide position" "original mutation description" "nucleotide mutation" "amino acid mutation" "amino acid mutation alias" "gene name" "gene symbol" "protein name" "protein symbol" "measured variant functional effect" "inferred variant functional effect" "viral life cycle functional effect" "variant functional effect description" "CVX code" "DrugBank Accession Number" "Antibody Registry ID" "author" "publication year" "URL" "DOI" "PMID" "peer review status" "curator" "mutation functional annotation resource" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "viral load" "" "" "This mutant causes a 0.41x fold change in the infectious virus production rate." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has a 0.66x fold change in EC50 value with Remdesivir." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has an inhibition rate of virus production by Remdesivir of 0.80." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has a 0.27x fold change in EC50 value with Remdesivir." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has an inhibition rate of virus production by Remdesivir of 0.78." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "viral load" "" "" "This mutant causes a 0.48x fold change in the infectious virus production rate." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.526 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.8x reduction in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,22992,23012,23664" "L5F,S477N,E484K,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 114 test-positive were Iota. Two dose vaccine efficacy against Iota was 95.7 (81.7-99.0%), one dose VE was 88.8 (0.7-98.7)%." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,25186" "L5F,Q1208H" "NC_045512.2:g.13C>T,NC_045512.2:g.3624G>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Gln1208His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Four of the convalescent sera tested showed 4-fold or greater improvement in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21587" "P9S" "NC_045512.2:g.25C>T" "YP_009724390.1:p.Pro9Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2M28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21597" "S12F" "NC_045512.2:g.35C>T" "YP_009724390.1:p.Ser12Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "A variant in low % circulation, predicted to have a similar effect to the experimentally verified S12P, which introduces a new signal peptide, altering cleavage to occur between residues C15 and V16, thereby eliminating the C15-C136 disulfide bond – similarly to escape mutants at positions C15 and C136. This in turn decreases to varying degrees N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600" "S13I" "NC_045512.2:g.38G>T" "YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The S13I mutation dampened binding of 5 mAbs and abrogated binding of 5 additional mAbs out of 11 neutralizing mAbs evaluated. Predicted to shift the signal peptide cleavage site from S13-Q14 to C15-V16, which can affect NTD conformation. PG: in saying S12F does not shift the signal peptide nor affect mAb binding, this manuscript appears to contradict the text of McCallum et al.'s earlier 2021 manuscript stating that S12F *does* affected some mAb binding via putative signal peptide shift." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018" "S13I,W152C" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The B.1.427/B.1.429 S13I/W152C NTD did not bind to any NTD-directed neutralizing mAbs, which are known to target a single antigenic site (antigenic site i), whereas binding of the non-neutralizing S2L20 mAb to the NTD antigenic site iv was not affected by any mutants, confirming proper retention of folding." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Antibody neutralization assays showed 6.7-fold resistance against 7/8 convalescent plasma." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Swab samples N/NP viral RNA is approximately 2-fold higher in B.1.427/B.1.429 than in non-variant viruses." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 9 plasma collected 15 to 28 days after early 2020 infections, neutralization reduced 4.9-fold for B.1.427/B.1.429 compared to wildtype (D614G). In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.427/B.1.429 pseudotyped virus, as well as WT and other VOCs." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using HIV pseudotype: Neutralization potency of 11 Moderna mRNA1273-elicited plasma (7-27 days post-2nd dose) was reduced ~2.8-fold compared to wildtype (D614G) S. It was reduced ~4-fold in 14 Pfizer/BioNtech BNT162b2-elicited plasma (7-27 days post-2nd dose). Using VSV pseudotype: we observed a 3-fold average reduction of Pfizer/BioNtech BNT162b2-elicited plasma neutralizing activity." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.249 (1.7-fold). Neutralization against 10 convalescent plasma was somewhat poorer (3.1-fold)." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "14 of 34 RBD-specific mAbs showed reduced neutralization to the B.1.427/B.1.429 variant pseudotype." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Lineages bearing these spike mutations comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the ""California"" or ""West Coast"" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI:1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020." "" "" "" "Peng" "2021" "https://doi.org/10.1093/cid/ciab283" "doi:10.1093/cid/ciab283" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.427/429 reduced 2.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "6 of 11 (55%) vaccine recipients (Moderna or Pfizer), showed 2x reduction in neutralization to a B.1.429 lineage virus." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 2.7x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 2.3x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403,25135" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G,K1191N" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3573G>T" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys1191Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for CAL.20C (B.1.429), and a slight decrease in CD8+ percentage (p=0.0201) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21604,21604" "Q14H,Q14H" "NC_045512.2:g.42G>C,NC_045512.2:g.42G>T" "YP_009724390.1:p.Gln14His,YP_009724390.1:p.Gln14His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21605" "C15R" "NC_045512.2:g.43T>C" "YP_009724390.1:p.Cys15Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21606" "C15F" "NC_045512.2:g.44G>T" "YP_009724390.1:p.Cys15Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates neutralization by N-terminal-domain-targeting mAbs 4-19. Impairs neutralization by N-terminal-domain-targeting mAbs 4A8 and 2-17." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggetsing that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132" "L18F,T20N,P26S,D138Y,R190S" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The neutralization titer of NTD-binding mAb159 was 133-fold reduced on P.1 compared to Victoria (~wild type), with only 64% neutralization at 10 μg/mL. Residues 20, 18, and 138 form a cluster underlying the 245–259 loop, which inserts into a groove between the light and heavy chains of Fab 159. In addition, the N-terminal residues preceding residue 18 interact with the antibody and may be perturbed. Given that there is likely a single supersite (""i"") for potent NTD-binding antibodies, the binding of many of these are likely affected. Using 20 potent (primaruly anti-RBD) antibodies, neutralization was measured by a focus reduction neutralization test (FRNT) and compared with neutralization of Victoria (~wild type) and variants B.1.1.7 and B.1.351. Compared to Victoria neutralization by the mAbs was significantly impacted by P.1, with 12/20 showing > 10-fold reduction in FRNT50 titer and a number showing complete knockout of activity. The results with P.1 showed a greater impact compared to B.1.1.7 but were, as expected, similar to those with B.1.351." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Amongst RBD-targeting Emergency Use Authorized monoclonal antibody treatments CB6, LY-CoV555 and REGN10933 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1, but REGN10987 activity remains strong. RBD-targeting monoclonal antibodies 2-15 and C121 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. N terminal domain targeting monoclonal antibodies 5-7, 4-8, 4-18 and 2-17 have abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 12 Moderna vaccinee sera 15 days post second dose (43 days since first vaccination), an average 2.8x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 4.8x decrease against the full P.1 type vs WA-1 was observed, though overall with a higher ID50 reciprocal value. In 10 Pfizer vaccinee sera 7 days or more post second dose (28 days or more since first vaccination), an average 2.2x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.8x decrease against the full P.1 type vs WA-1 was observed, with similar variant ID50 reciprocal value." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the “up” position." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In convalescent sera one month or more post-infection in Spring 2020, an average 6.5x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.4x decrease against the full P.1 type vs WA-1 was observed, with better full P.1 ID50 reciprocal value compared to the 10-mutation model." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "After a 128 day interval, a patient in Sao Paulo State, Brazil reinfected with P.1 (first episode likely predates P.1 emergence). Both cases were fairly mild (difficulty breathing, tiredness, dizziness and fatigue)." "" "" "" "Malta Romano" "2021" "https://doi.org/10.1590/S1678-9946202163036" "doi:10.1590/S1678-9946202163036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Gamma (P.1) variant is 0.6x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 3.0x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 4.1x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 349 test-positive were Gamma. Two dose vaccine efficacy against Gamma was 95.5 (90.9-97.8%), one dose VE was 74.2 (43.8-88.1%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Three healthcare workers (29-50yo) had confirmed P.1 [Gamma] re-infection in the Amazonas region of Brazil 3-9 months after initial infection from viruses with distinct lineage from P.1, but mild symptoms upon re-infection and evidence for infectiousness during re-infection." "" "" "" "Naveca" "2021" "https://doi.org/10.21203/rs.3.rs-318392/v1" "doi:10.21203/rs.3.rs-318392/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x cleavage of S2 relative to WA1 (D614G) wildtype by Gamma variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but H655Y is upstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly lower against B.1.1.248 variant constellation in sera tested from most of the 15 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped P.1 virus has reduced neutralization activity vs wild type: 6.7x (30 sera Pfizer median 9 days post 2nd dose) and 4.5x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Unlike wild type or B.1.1.7, P.1 lineage virus was able to infect and replicate in common lab mouse strains, with high titer." "" "" "" "Montagutelli" "2021" "https://doi.org/10.1101/2021.03.18.436013" "doi:10.1101/2021.03.18.436013" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.248 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07. B.1.1.248 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.7 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0039 for mild resistance." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.248 variant constellation in 10 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples, P=0.0020." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 16.6% in this B.1.1.248 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Among 46,884 HCWs in Manaus, Brazil vaccinated with at least one dose of CoronaVac, a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%; 95% CI, 11.3 - 71.4) in the odds of symptomatic SARS-CoV-2 infection was observed during the period 14 days or more after receiving the first dose. Estimated vaccine effectiveness of at least one dose against any SARS-CoV-2 infection was 35.1% (95% CI, −6.6 - 60.5) in the same time period." "" "" "" "Hitchlings" "2021" "https://doi.org/10.1101/2021.04.07.21255081" "doi:10.1101/2021.04.07.21255081" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.15x *increase* in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Neutralizing antibodies that were generated following a mild infection with SARS-CoV-2 B.1.128 were effective in vitro, and likely protective, against the SARS-CoV-2 P.1. variant in the majority of individuals based on 60 convalescent sera tested." "" "" "" "Mendes-Correa" "2021" "https://doi.org/10.1101/2021.05.11.21256908" "doi:10.1101/2021.05.11.21256908" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "VSV pseudotype P.1 showed 4.8-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections)." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype P.1 showed slight decrease in cell entry relative to wild type in 262T and 263T-ACE2 (kidney) cell lines. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "VSV pseudotype P.1 entry mediated by the S proteins of the P.1 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Cell fusion proficiency was slight impaired. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for P.1 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the P.1 variants used, using the most popular as a stand in]" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against P.1 at various time points using pseudovirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 85%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 256 for B.1.1.7 virus. Compare to somewhat stronger neutralization titer for wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "PBMCs of 11 mild COVID-19 patients collected 38-80 days after symptom onset were stimulated with the 15-mer peptide pools (w/ 10 residue overlaps) from the wholle viral proteome, showing no significant CD4+ cell count effect for P.1, and a slight increase in CD8+ percentage (p=0.0195) by Activation Induced Marker (AIM) assay (cellular immunity measurement). [in the text, this increase is not noted as signficant, even though p=0.05 is used elsewhere in the text as a signficance threshold]" "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "P.1 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with Lilly mAb combination LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of P.1. There was also escape from neutralization of P.1 by REGN10933 (one of 2 in Regeneron's mAb cocktail) and a modest reduction in neutralization of P.1 by AstraZeneca's AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized P.1 with all reaching a plateau at 100% neutralization; interestingly, ADG30 showed a slight increase of neutralization of P.1. S309 Vir was largely unaffected, although for several viruses, including P.1, the antibody failed to completely neutralize, conceivably reflecting incomplete glycosylation at N343, since the sugar interaction is key to binding of this antibody." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The relative transmissibility of P.1 estimated at the national level (Italy) varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. PG: variant list has been abbreviated due to mixed K417 bases in this lineage, potential miscalls of deletions" "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21801,22206,22334,22600,22600,22810,22811,22812,22813,22813,22879,22881,22882,22882,22986,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D80A,D215G,W258R,R346S,R346S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,A475V,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.772T>C,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1424C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ala475Val,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments and mutations from variants of concern completely ablates neutralization in 19 of 21 convalescents plasma collected mean 1.3 months post infection. [actual Y145del from manuscript substituted with more common Y144del description]" "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801" "L18F,D80A" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The L18F and D80A of the B.1.351 lineage lead to reconfiguration of the N-terminal segment despite the disulfide between Cys16 and Cys136 that partly anchors the N-terminal peptide. The most consequential changes are probably from the triple residue deletion... which causes a shift of the nearby loop 144-155 and must also reconfigure the adjacent disorder loop (residues 246-260), both of which form part of the neutralizing epitopes...bringing large changes in the antigenic surface in this region." "" "" "" "Cai" "2021" "https://doi.org/10.1101/2021.04.13.439709" "doi:10.1101/2021.04.13.439709" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The 501Y.V2 to first wave IC50 ratio ranged from 6 to 200-fold. Averaging across all 7 participant convalescent sera highlighted the dramatic decrease in sensitivity to neutralization of authentic 501Y.V2 variants. PG: I'm purposefully ignoring D614G and A701V as contributors" "" "" "" "Cele" "2021" "https://doi.org/10.1038/s41586-021-03471-w" "doi:10.1038/s41586-021-03471-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~7-fold reduction in B.1.351 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike)." "" "" "" "Riddell" "2021" "https://doi.org/10.1101/2021.04.17.440246" "doi:10.1101/2021.04.17.440246" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike)." "" "" "" "Riddell" "2021" "https://doi.org/10.1101/2021.04.17.440246" "doi:10.1101/2021.04.17.440246" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pzifer vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1), but were all infected before 14 days post second vaccination." "" "" "" "Kustin" "2021" "https://doi.org/10.1101/2021.04.06.21254882" "doi:10.1101/2021.04.06.21254882" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals (5/9) and recipients of a only a single dose of mRNA vaccine (10/11) – heterotypic neutralization dropped to negligible levels, particularly against B.1.351." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR22 molecule had a 1.57x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "B.1.351 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of B.1.351. There was also escape from neutralization of B.1.351 by REGN10933 and a modest reduction in neutralization of B.1.351 by AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized B.1.351." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.054x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 8 for B.1.351 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Sera from individuals who have been infected with Delta does not have strong neutralising activity against Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Beta neutralizing antibodies is 0.803x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.351. We observed an increase (relative to D614G) in binding of soluble ACE2 to B.1.351, and to a much gearter extent to B.1.1.7, which both carry the N501Y mutation (see Fig 3)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Pseudotype lentivirus for the full B.1.351 Spike variant list shows increase affinity for ACE2 as measured by IC50. This is in contrast to B.1.1.7 which showed no major change, indicating that the shared N501Y mutation is the driver of affinity change, attentuated in the B.1.1.7 mutatioon set, but maintained in the B.1.351 lineage." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 6.3x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Beta Variant B.1.351 RBD significantly better than w.t. SARS-CoV-2 RBD. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.07x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed for B.1.351 a CD4+ cell count decrease (29%, p=0.00063) as well as CD8+ (33%, p=0.0016) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Encouragingly, we find that the majority of T cell responses in recipients of two doses of the BNT162b2 vaccine are generated by epitopes that are invariant between the [wildtype] and two of the current variants of concern (B.1.1.7 and B.1.351). In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals and recipients of a only a single dose of mRNA vaccine – heterotypic neutralization dropped to negligible levels, particularly against B.1.351." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 8.2x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 16/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.351, with similar results for the live virus." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Beta neutralizing antibodies is 0.899x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v2 virus has reduced neutralization activity vs wild type: 41.2x (30 sera Pfizer median 9 days post 2nd dose) and 20.8x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v2 reduced 7.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.351 sample. Contrast this with 1.4-fold reduction for just the pseudovirus combination of ""key"" B.1.351 mutations K417N+E484K+N501Y. WA1 and B.1.351 FRNT50 titers correlated weakly at the individual level, with some individual’s serum potently neutralizing WA1 while having FRNT50 for B.1.351 below the assay limit of detection (1:20)." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.351 pseudotyped virus model ablates neutralization by RBD-directed mAbs CB6, 4-20, 2-4, 2-43, 910-30, 2-302-15, LY-Cov555, C121. B.1.351 pseudotyped virus model severely impairs neutralization by RBD-directed mAb 1-20. B.1.351 pseudotyped virus model impairs neutralization by RBD-directed mAb REGN10933. B.1.351 pseudotyped virus model ablates neutralization by N-terminal-domain-directed mAbs 5-24, 4-8, 4A8, 4-19. B.1.351 pseudotyped virus model severely impairs neutralization by N-terminal-domain-directed mAb 2-17. B.1.351 pseudotyped virus model impairs neutralization by N-terminal-domain-directed mAb 5-7. PG: Live virus data for the same mAbs is similar, but 1-20 becomes severally impaired, REGN10933 activity is ablated, and Brii-196 becomes impaired." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "3.2x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "[Contrary to how this paper has been cited, Voysey et al. do NOT show evidence of decreased effectiveness of ChAdOx1 (AstraZeneca) against the South African B.1.351 lineage. Insufficient numbers reaching the primary study endpoint were available in that arm of the vaccine study to report any statistics from the South African participants. Additionally, the study period of the paper ended in November 2020, while the earliest reported case of this lineage is October (covariants.org), only becoming dominant by mid-November.]" "" "" "" "Voysey" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms had mean ~6x reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: while B.1.1.7 and D614G showed neutralization by nasal swab from only one different previously infected vacinee neutralizing at weeks 3 and 6, B.1.351 showed zero neutralization at either time point in any sample (and relatively impaired serum neutralization)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "A 1.8-fold drop in FRNT50 for B.1.351 was observed in 44 sera collected between 1 and 301 post-infection." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 0.036x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 99.7x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 6.7x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with all key mutations from B.1.351 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting some synergy between the mutations to decrease cell entry fitness (i.e. cell entry is liklely not the driver of this lineage's dominance)." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,23060,23061,23062,23063,22810,22811,22812,22813,22813,23012,23399,23401,23402,23403" "L18F,D80A,D215G,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The most significant loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against authentic B.1.351 lineage virus (9.2-fold). Neutralization against 10 convalescent plasma was poorer (18.7x)." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks." "" "" "" "Meister" "2021" "https://doi.org/10.1093/infdis/jiab260" "doi:10.1093/infdis/jiab260" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Parana state of Brazil, patients aged 20-29 years experienced a tripling of their case fatality rate (CFR), from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling comparing February to January in 2021. Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil. [this is somewhat indirect evidence that assume greatly increasing proportion of P.1 cases in March (70%) compared to February, but the first official ID of P.1 in Parana state (Feb 16th) may be due to testing procedures rather than actual prevalence]" "" "" "" "Santos de Oliviera" "2021" "https://doi.org/10.1101/2021.03.24.21254046" "doi:10.1101/2021.03.24.21254046" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22915,22916,22917,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 (Pfizer) vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains." "" "" "" "Mallm" "2021" "https://doi.org/10.1101/2021.04.27.21254849" "doi:10.1101/2021.04.27.21254849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Delta (B.1.617.2) shows mean 2.1x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Delta (B.1.617.2) shows 3.64x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22916,22917,23012,23399,23401,23402,23403" "T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this lineage defining mutation combination from B.1.617.3 increased syncytium formation ~2.3x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22916,22917,23012,23399,23401,23402,23403" "T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this lineage defining mutation combination from B.1.617.3 conferred a ~11.8x drop in neutralization (NT50) [suggesting role for T19R and T95I in half the sera]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22916,22917,23012,23399,23401,23402,23403" "T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this lineage defining mutation combination from B.1.617.3 conferred a ~4.5x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,23399,23401,23402,23403" "T19R,T95I,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22028,22915,22916,22917,23604,23399,23401,23402,23403,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,E156del,L452R,L452R,L452R,P681R,D614G,D614G,D614G,D614G,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.467_472del,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4.5x cleavage of S2 relative to WA1 (D614G) wildtype by Delta (B.1.617.2) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~3.5x for closely related Kappa B.1.617.1 also with P681R at the cleavage site)." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. [Mutation list in publication appears to contain a typo with R158del instead of R158G]" "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 4.0x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Modelling the Delta variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increased 11x relative to wild type (15.3 vs 1.4). [del ~157 truncated due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a coinfection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 2.6x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.020x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.10x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In primary human airway epithelial cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 1.9x relative to wild type (2.7 vs 1.4). This is the Delta variant with the P681R furin cleavage site mutation absent. [del ~157 truncated due to ambiguity]" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Plasma neutralizing activity was also assessed against SARS-CoV-2 Delta, Omicron BA.1, BA.2 and BA.4/5 variants using viruses pseudotyped with appropriate variant spikeproteins. Delta breakthrough infection resulted in 15-fold increased neutralizing titers." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Plasma neutralizing activity in 49 participants was measured using HIV-1 pseudotyped with the 100 WT SARS-CoV-2 spike protein. Delta breakthrough infection resulted in 11-fold increased geometric mean half-maximal neutralizing titer (NT50)." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Delta neutralizing antibodies is 0.872x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Delta Variant B.1.617.2 RBD or w.t. SARS-CoV-2 RBD with nearly equal potency determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 507 pM for binding to the Delta B.1.617.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Delta neutralizing antibodies is 0.952x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "The incidence rate of Covid-19 during the Delta-dominant period (Jul-Aug 2021) was lower for late vaccinated (49.0/1000 person-years) [formerly placebo] versus early vaccinated (77.1/1000 person-years) participants in the Moderna mRNA-1273 Phase 3 trials, representing a 36.4% VE reduction (95% CI 17.1%-51.5%). There were fewer severe Covid-19 cases in the late group (6; 6.2/1000 person-years) than early (13; 3.3/1000 person-years), representing a 46.0% reduction (95% CI −52.4%-83.2%). Three Covid-19 related hospitalizations occurred with two resulting deaths in the early group." "" "" "" "Baden" "2021" "https://doi.org/10.1101/2021.09.17.21263624" "doi:10.1101/2021.09.17.21263624" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.92x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Delta Molnupiravir (MK-4482) had ~4x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001)." "" "" "" "Chia" "2021" "https://doi.org/10.1101/2021.07.28.21261295" "doi:10.1101/2021.07.28.21261295" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001)." "" "" "" "Chia" "2021" "https://doi.org/10.1101/2021.07.28.21261295" "doi:10.1101/2021.07.28.21261295" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance." "" "" "" "Twohig" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance." "" "" "" "Twohig" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccination of health care workers in Delhi was started in early 2021, with the ChdOx-1 (Astra Zeneca) vaccine. Surveillance has suggested B.1.1.7 dominance in the Delhi area during early 2021, with growth of B.1.617 since March 2021. During the wave of infections during March and April an outbreak of SARS-CoV-2 was confirmed in 33 vaccinated staff members at a single tertiary centre (age 27-77 years). Sequencing revealed that 16/33 were B.1.617.2, with a range of other B lineage viruses including B.1.1.7 for the rest except one A lineage case. Importantly no severe cases were documented in this event." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Case 62541 cluster in Singapore included a fully vaccinated nurse 2 months post-vaccine [likely Pfizer based on dates and supply], and a doctor of unknown vaccine status. This cluster was caused by a B.1.617.2 virus [via crossreference to" "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Denmark, for the period Jan 1 to Jun 27, 2021, Delta variant was associated with increased an risk ratio of 2.83 [95% CI 2.02–3.98] for hospitalization." "" "" "" "Bager" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.2 aka Delta) showed a 2.34x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.89x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Delta (B.1.617.2) has an IC50 fold change of 46.5x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Delta (B.1.617.2) variant is 0.6x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Delta (B.1.617.2) has an IC50 fold change of 0.57x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Delta (B.1.617.2) has an IC50 fold change of 0.87x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,E156del,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Delta (B.1.617.2) has an IC50 fold change of 0.15x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,23399,23401,23402,23403" "T19R,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21627" "T22I" "NC_045512.2:g.65C>T" "YP_009724390.1:p.Thr22Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain, frequently observed in various human infection lineages, reduces the tropism of SARS-CoV-2 in F81 (cat kidney, Felis catus) and BHK-21 (golden hamster kidney, Mesocricetus auratus) cell line cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21648" "T29I" "NC_045512.2:g.86C>T" "YP_009724390.1:p.Thr29Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21717,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23399,23401,23402,23403,23593,23593,24224" "Q52R,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,D614G,D614G,D614G,D614G,Q677H,Q677H,F888L" "NC_045512.2:g.155A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C" "YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.525 reduced 4.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21717,23012,23593,23593,24224" "Q52R,E484K,Q677H,Q677H,F888L" "NC_045512.2:g.155A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C" "YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The B.1.525 appears to have poor transmissibility when in competition with B.1.1.7 and other circulating strains in Denmark (early 2021)." "" "" "" "Albertsen" "2021" "https://www.covid19genomics.dk/2021-05-08_data-overview.html#b1525" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21752,21752" "W64R,W64R" "NC_045512.2:g.190T>A,NC_045512.2:g.190T>C" "YP_009724390.1:p.Trp64Arg,YP_009724390.1:p.Trp64Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21759" "H66R" "NC_045512.2:g.197A>G" "YP_009724390.1:p.His66Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent, especially on a D614 wildtype background." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Neutralization activity of almost all Moderna Phase 1 sera tested actually *increased*." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This deletion outside the receptor binding domain in pseudotyped VSV promoted the capacity of pseudotyped VSV to transduce black flying fox (Pteropus alecto) kidney PabKi.1 cells (17.8%) to a level twice that of human epithelial-like Huh-7 cells (9.8%)" "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduces neutralization by structurally unmapped mAb COVA1-21 (cluster XI)." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization activity of almost all convalescent sera tested decreased ~2x." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "The delH69/V70 enhances viral infectivity, indicating its effect on virus fitness is independent to the N501Y RBM change [with which it is found in lineage B.1.1.7] Possibly arisen as a result of the virus evolving from immune selection pressure in infected individuals and possibly only one chronic infection in the case of lineage B.1.1.7." "" "" "" "Kemp" "2020" "https://doi.org/10.1101/2020.12.14.422555" "doi:10.1101/2020.12.14.422555" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No notable change in neutralization efficiency, despite N439K by itself showing a ~2x decrease on average in 16 health workers' convalescent sera." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization activity of convalescent sera tested decreased ~2x with this B.1.1.7 pseudotyped virus." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron (a.k.a. B.1.1.529) Spike pseudotyped VSV and Vero E6 cells has somewhat reduced neutralization (2.7x) vs wild type with monoclonal antibody Sotrovimab (a.k.a. VIR-7831). [delins at 214 omitted for syntax compatibility]" "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron breakthrough infection after 3-dose vaccination resulted in a further 3.5-fold and 2.9-fold increase of Omicron BA.1 and BA.2 neutralizing titers. Omicron BA.4/5 showed the highest neutralization resistance of all variants tested, resulting in low geometric mean neutralizing titers in plasma samples obtained after the second vaccine dose (NT50=72)." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron B.1.1.529 (BA.1) neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron (B.1.1.529 [BA.1]) have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Omicron variant and was used to determine neutralizing antibodytitres. There was a 114.84x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 6.61x fold increase in antibody response pre-reinfection. There was a 1194.9x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Omicron BA.1 variant is 1.0x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.1 has an IC50 fold change of 0.30x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 73 pM for binding to the Omicron B.1.1.529. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigms’ ACE-2 variant LVE/STR chimera binds to SARS-2 Omicron variant B.1.1.529 spike protein trimer with high affinity. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Omicron BA.1 has an IC50 fold change of 1.26x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Delta variant and was used to determine neutralizing antibodytitres. There was a 24.63x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 4.21x fold increase in antibody response pre-reinfection. There was a 39.27x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.1 has an IC50 fold change of 0.08x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Omicron BA.1 has an IC50 fold change of 0.38x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "All 10 individuals with 3 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 3319 NT50." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "All 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 729 NT50." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against B.1 variant and was used to determine neutralizing antibodytitres. There was a 6.76x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 2.06x fold increase in antibody response pre-reinfection. There was a 8.18x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.3 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.3 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was somewhat lower against B.1.1.7 in sera tested from most of the 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.7 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2489." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.1.7 sample. Contrast this with 1.3-fold reduction for just the pseudovirus combination of ""key"" B.1.1.7 mutation N501Y." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild to modest decrease in infection rate amongst the cells, suggesting a net mild negative effect on human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing moderate decrease in infection rate amongst the cells, significantly lower than the deletion or Y453F alone, or their combination, suggesting a synergistic effect on poorer human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, much closer to D614G activity level than Y453F alone, suggesting compensatory effects between the deletion and the mutation in human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,23399,23401,23402,23403,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,D614G,D614G,D614G,D614G,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.298 virus has reduced neutralization activity vs wild type: 1.4x (30 sera Pfizer median 9 days post 2nd dose) and 1.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells, markedly higher infectivity than either mutation alone, suggesting a synergistic net neutral effect on human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from Mink Cluster 5 was neutralized more easily than D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with all key mutations from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (~50%) decrease in infection rate amongst the cells, suggesting that this anthropozoonotic event is driven by other factors at the expense of human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7+E484K reduced 2.8x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Compare with 1.2x reduction for B.1.1.7 without E484K." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization capacity GMT of 27 subjects' sera post-infection was markedly worse against B.1.1.7 + E484K than the lineage alone, with a 11.4x drop." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation combination causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x). PG: these effects are laregly missing in the deletion-alone data" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." "" "" "" "van Loon" "2021" "https://doi.org/10.1101/2021.04.15.21255389" "doi:10.1101/2021.04.15.21255389" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "In comparison of B.1.1.7 lineage (193 cases) vs. ""wildtype"" (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." "" "" "" "van Loon" "2021" "https://doi.org/10.1101/2021.04.15.21255389" "doi:10.1101/2021.04.15.21255389" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "A higher proportion of cases infected with the B.1.1.7 variant were hypoxic on admission compared to other variants (70.0% vs 62.5%, p=0.029), in London between March 13th 2020 and February 17th 2021 (400 B.1.1.7 cases out of 1470 total sequenced)." "" "" "" "Snell" "2021" "https://doi.org/10.1101/2021.03.16.21253377" "doi:10.1101/2021.03.16.21253377" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, moreso than this combination with the addition of P681H." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "clinical indicators" "" "" "After adjusting for the age factor, in a prospective Chinese cohort study B.1.1.7 variant infection (compared to B.1.140) was the risk factor for C-reactive protein (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), Serum amyloid A (0.011, 5.031, [1.459, 17.354]), Creatine Kinase (0.034, 4.34, [0.05, 0.91]), CD4+ T lymphocyte (0.029, 3.31, [1.13, 9.71]), and Ground Glass Opacity (0.005, 5.418, [1.656, 17.729])" "" "" "" "Song" "2021" "https://doi.org/10.1101/2021.05.04.21256655" "doi:10.1101/2021.05.04.21256655" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion)." "" "" "" "Marquez" "2021" "https://doi.org/10.1017/ice.2021.195" "doi:10.1017/ice.2021.195" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Second infection in December 2020 with B.1.1.7 after April 2020 initial infection with B.2 in a 78-year-old man with a history of Type 2 diabetes mellitus, diabetic nephropathy on hemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnea, ischemic heart disease, with no history of immunosuppression." "" "" "" "Harrington" "2021" "https://doi.org/10.1093/cid/ciab014" "doi:10.1093/cid/ciab014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM for binding to the Alpha B1.1.7. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Lessens the potency of mAbs COVA2-17 (~5x, similar to N501Y alone), COVA1-12 (~11x) and COVA1-21 (>100x), which do not compete allosterically." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 1.7x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.7 pseudotyped virus model impairs binding by RBD-directed mAb 910-30. B.1.1.7 pseudotyped virus model abolishes N-terminal-domain-directed mAbs 5-24, 4-8, and 4A8. B.1.1.7 pseudotyped virus model impairs binding by N-terminal-domain-directed mAbs 2-17, 4-19, 5-7." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020. Possible reinfections were identified in 249 (0.7% [95% CI 0.6-0.8]) of 36509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants." "" "" "" "Graham" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20x resistence to mAb CQ038 by B.1.1.7 pseudotyped virus" "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Alpha Variant B.1.1.7 RBD significantly better than GenScript IgG FL18-740 w.t. ACE-2 mAB. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.1.7. We observed a dramatic increase (relative to D614G) in binding of soluble ACE2 to B.1.1.7, and to a lesser extent to B.1.351, which both carry the N501Y mutation (see Fig 3)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion)." "" "" "" "Marquez" "2021" "https://doi.org/10.1017/ice.2021.195" "doi:10.1017/ice.2021.195" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%)." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "aerosolization" "" "" "Alpha variant cases in a large campus study showed fine-aerosol shedding amongst unmasked participants remained significantly greater for alpha variant infections (18-fold, 95% CI, 3.4 to 92-fold) after adjusting for the increased viral RNA in MTS and saliva, the number of coughs during sampling sessions, and symptom. After controlling for the effect of masks and numbers of coughs during sampling, alpha variant infection was associated with a 100-fold (95% CI, 16 to 650-fold) increase in coarse- and a 73-fold (95% CI, 15 to 350-fold) increase in fine-aerosol RNA shedding." "" "" "" "Adenaiye" "2021" "https://doi.org/10.1093/cid/ciab797" "doi:10.1093/cid/ciab797" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2.5x cleavage of S2 relative to WA1 (D614G) wildtype by Alpha variant variant as measured by mass spectrometry of Vero-TMPRSS culture." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "First documented cases of domestic cat and dog infections with the B.1.1.7 strain." "" "" "" "Hamer" "2021" "https://doi.org/10.1111/tbed.14122" "doi:10.1111/tbed.14122" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 2.6x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the 47D10. Alpha (B.1.1.7) has an IC50 fold change of 0.40x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks." "" "" "" "Meister" "2021" "https://doi.org/10.1093/infdis/jiab260" "doi:10.1093/infdis/jiab260" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively." "" "" "" "Schuit" "2021" "https://doi.org/10.1093/infdis/jiab171" "doi:10.1093/infdis/jiab171" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively." "" "" "" "Schuit" "2021" "https://doi.org/10.1093/infdis/jiab171" "doi:10.1093/infdis/jiab171" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.44x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM analysis of B.1.1.7 demonstrates an increased propensity for 'up', receptor accessible conformation of the Spike protein trimer." "" "" "" "Cai" "2021" "https://doi.org/10.1101/2021.04.13.439709" "doi:10.1101/2021.04.13.439709" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 2/20 (10%) samples showed >10x reduction (sera collected ~1mo post Jan 2020 first wave in China). Neutralizing antibody titers of 8/20 samples (40%) decreased below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaulated against VSV pseudotypes: neutralized D614G at week 2, whereas B.1.1.7 started to be neutralized at week 3, although less efficiently than D614G. B.1.1.7 and D614G strains were similarly neutralized at week 4 (1 week after booster dose)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We observed a sharp decline in cases when ∼50% of the elderly population was 2 weeks beyond their first vaccination dose and at a time point during which the B.1.1.7 variant gained transmission dominance. In support of this finding, it was suggested that, after the first vaccination dose, more than 70% of patients develop neutralization antibodies,15 and the vaccine efficiency can reach 85%." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Live virus was tested ex vivo in reconstituted brochial epithelium, and out competed wild type." "" "" "" "Touret" "2021" "https://doi.org/10.1101/2021.03.22.436427" "doi:10.1101/2021.03.22.436427" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.39x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization assays of B.1.1.7 virus showed a reduction of 2.5-fold (14 days post 2nd dose AstraZeneca, n=15), 2.1-fold (28 days post 2nd dose AstraZeneca, n=10), and 3.3-fold (7-17 days post 2nd dose Pfizer-BioNTech, n=25). [D1119H was included in the original paper, assumed typographical error and changed to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 1 (B.1.1.7) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "NTD-specific nAbs showed a substantial (3-450x) decrease in neutralization potency against the recently reported highly transmissible B.1.1.7 variant of concern, whereas RBD-specific nAbs were either unaffected or showed lower decreases in potency." "" "" "" "Graham" "2021" "https://doi.org/10.1016/j.immuni.2021.03.023" "doi:10.1016/j.immuni.2021.03.023" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Modelling the Alpha variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 3.9x relative to wild type (5.4 vs 1.4). This is less efficient than Delta (11x vs wildtype using a P681R mutation instead). [del ~144 changed due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a co-infection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 virus has reduced neutralization activity vs wild type: 2.1x (30 sera Pfizer median 9 days post 2nd dose) and 2.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Note that Y145del was actually noted in the paper as the effect of their DNA construct, but this is equivalent at the protein level to the more commonly annotated Y144del." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Alpha (B.1.1.7) variant is 1.0x fold the wildtype in 42 COVI." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Alpha Molnupiravir (MK-4482) had ~2.75x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "NVX-CoV2373 [Novavax] vaccine in phase 3 trial was 89.7% (95% CI, 80.2-94.6) effective in preventing COVID-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8-99.5) and 86.3% (71.3-93.5) against the prototype strain and B.1.1.7 variant, respectively." "" "" "" "Heath" "2021" "https://doi.org/10.1101/2021.05.13.21256639" "doi:10.1101/2021.05.13.21256639" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Alpha (B.1.1.7) has an IC50 fold change of 1.19x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.1.7 lineage effectiveness was observed as 29.5% (95% CI [22.9,35.5]) against infection, and 54.1% against severe/critical/fatal disease (95% CI [26.1-71.9]). Two weeks or more after 2nd dose, effectiveness climbed to 89.5% [85.9,92.3] against infection, and 100% against severe/critical/fatal disease (95% CI [81.7,100])." "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24506" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,S982A" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Lilly's LY-CoV16 showed marked reduction in neutralization of B.1.1.7." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Sera neutralized the B1.1.7 isolate with a lower potency (2-fold; 95% CL: 1.5 – 3-fold), and those with the lowest homotypic neutralizing potency had undetectable heterotypic potency (2/25)." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23399,23401,23402,23403,23709,23604,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,T716I,P681H,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific replication effects" "" "" "In this report, by using a lower infectious dose, we demonstrate that B.1.1.7 (cultured sample Hong Kong/HKPU-00015/2021) exhibits higher infectivity and/or replication efficiency in the nasal epithelium. (Hamster model of infection)" "" "" "" "Mok" "2021" "https://doi.org/10.1101/2021.04.19.440414" "doi:10.1101/2021.04.19.440414" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7." "" "" "" "Graham" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7." "" "" "" "Graham" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies." "" "" "" "Muik" "2021" "https://doi.org/10.1126/science.abg6105" "doi:10.1126/science.abg6105" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies." "" "" "" "Muik" "2021" "https://doi.org/10.1126/science.abg6105" "doi:10.1126/science.abg6105" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The mortality hazard ratio associated with infection with [B.1.1.7] compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community (54906 matched pairs of participants who tested positive for SARS-CoV-2 in pillar 2 between 1 October 2020 and 29 January 2021). In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases." "" "" "" "Challen" "2021" "https://doi.org/10.1136/bmj.n579" "doi:10.1136/bmj.n579" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "20/29 sera after the first dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 variant of 3.2 ± 5.7. After the second dose, the GMT was markedly increased compared with the first-dose titres, with a fold change of 1.9 ± 0.9 (mean ± s.d.). Neutralization GMT of 27 subjects post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization capacity GMT of 27 subjects' sera post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (""UK variant""). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 ""wild type"" SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036)." "" "" "" "Song" "2021" "https://doi.org/10.1101/2021.05.04.21256655" "doi:10.1101/2021.05.04.21256655" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype B.1.1.7 showed no significant difference in cell entry relative to wild type in 6 cell lines. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020, Rt of B.1.1.7 was 1.35x (95% CI 1.02-1.69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant." "" "" "" "Graham" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, but to a smaller extent than N501Y and the deletion alone." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Slight neutralization improvement on average in 16 health workers' convalescent sera." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "These key B.1.1.7 mutations as a combination neutralized slightly less well than D614G and this was noticeable in the lack of sera with high neutralizing titer for the viruses across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,21762,21763,21764,21765,21766,21766,23399,23401,23402,23403,22915,22916,22917" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 17.2x-fold lower (95% CI: 0.6x-0.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,21762,21763,21764,21765,21766,21766,23399,23401,23402,23403,22915,22916,22917" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 13.0-fold lower (95% CI: 4.2x-4.6x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,22810,22811,22812,22813,22813,23009,23010,23012,23013" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,K417N,K417N,K417N,K417N,K417N,E484A,E484A,E484A,E484A" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario, using a retrospective matched case (age, gender and onset date) study of 6,312 Omicron cases vs 8,875 Delta, the adjusted risk of hospitalization or death was 54% lower (HR=0.46, 95%CI: 0.27, 0.77) among Omicron cases, after adjusting for vaccination statis and time since 2nd shot. The ratio for >60yo was 0.55 (95%CI: 0.28-1.06), and <60yo was 0.30 (95%CI: 0.16-0.57)." "" "" "" "Ulloa" "2021" "https://doi.org/10.1101/2021.12.24.21268382" "doi:10.1101/2021.12.24.21268382" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21761,21762,21763,21764,21765,21766,21766,23009,23010,23012,23013" "H69del,H69del,H69del,H69del,H69del,H69del,H69del,E484A,E484A,E484A,E484A" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection, evidenced by a reinfection hazard ratio of 2.39 (CI95: 1.88-3.11) relative to primary infection in the initial part of South Africa's 4th covid-19 wave (November 2021). In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. [minimal variant signature for Omicron (B.1.1.529) used based on H69del PCR dropout observed in November 2021 coincident with the rise of Omicron]" "" "" "" "Pulliam" "2021" "https://doi.org/10.1101/2021.11.11.21266068" "doi:10.1101/2021.11.11.21266068" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800" "D80N" "NC_045512.2:g.238G>A" "YP_009724390.1:p.Asp80Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800" "D80Y" "NC_045512.2:g.238G>T" "YP_009724390.1:p.Asp80Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This AA substitution outside the receptor binding domain in pseudotyped VSV promoted a 7.2% transduction rate in golden hamster cells, which was higher than that of human epithelial-like Huh-7 cells (6.6%)." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800,22188,22206,22597,22599,23012,23521,23522,23524,23525,23604" "D80Y,I210del,D215G,R346K,R346K,E484K,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.238G>T,NC_045512.2:g.629_631del,NC_045512.2:g.644A>G,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp80Tyr,YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.VOI.V2 (first identified in Angola) reduced 8.0x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated that there is no free energy change (ddG) for this variant (i.e. same stability as wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "One individual of 30 in the study, with HLA supertype HLA*A24:02, had a linear epitope that overlaps this variant of concern." "" "" "" "Redd" "2021" "https://doi.org/10.1101/2021.02.11.21251585" "doi:10.1101/2021.02.11.21251585" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolishes neutralizing activity of N-terminal-domain-directed mAb 4-19." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.351 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 71%, Day 209 54%. Detectable antibodies against B.1.351 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 79%, Day 209 58%. Detectable antibodies against B.1.351 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 63%, Day 43 100%, Day 119 71%, Day 209 79%. Decreased neutralization on some assays was seen especially in those vaccinees tested that were 71+." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In an Ontario long term care facility, cumulatively, weaker BNT162b2 vaccine stimulation, age/comorbidities, produced a ∼130-fold reduction in apparent neutralization titers in mean 88yo LTCH residents against Beta (B.1.351), relative to staff vaccinees against D614G wild type. 37.9% of 116 two-dose-mRNA-vaccinated residents had undetectable neutralizing antibodies to B.1.351. mRNA-1273 vaccinee sera displayed ~2 better neutralization than BNT162b2. [common defining B.1.351 mutations noted, as the manuscript does not provide details]" "" "" "" "Abe" "2021" "https://doi.org/10.1101/2021.08.06.21261721" "doi:10.1101/2021.08.06.21261721" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, 7 of 15 neutralized this B.1.351 pseudotype that includes the L242del, and only one had titers above 100. Only one of the 15 sera achieved 80% neutralization. [compare to 5 and 1 for pseudotype without the deletion]" "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~10-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~3 fold without the deletion] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were significant, but ~500x weaker than in previously infected patients after first dose." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v3 reduced 8.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Beta (B.1.351) variant is 0.4x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A two-dose regimen of (AstraZeneca) ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, vaccine efficacy against severe Covid-19 is undetermined." "" "" "" "Madhi" "2021" "https://doi.org/10.1101/2021.02.10.21251247" "doi:10.1101/2021.02.10.21251247" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination." "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Unlike wild type or B.1.1.7, B.1.351 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. PG: The virus used in these expriments has a non-typical deletion+sub in the 242 region." "" "" "" "Montagutelli" "2021" "https://doi.org/10.1101/2021.03.18.436013" "doi:10.1101/2021.03.18.436013" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Beta (B.1.351) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Beta (B.1.351) has an IC50 fold change of 0.15x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x cleavage of S2 relative to WA1 (D614G) wildtype by Beta variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but A701V is downstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Beta Molnupiravir (MK-4482) had ~1.75x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v1 virus has reduced neutralization activity vs wild type: 34.5x (30 sera Pfizer median 9 days post 2nd dose) and 27.7x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Beta (B.1.351) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination." "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Compared to Alpha (B.1.1.7) variant, odds of progressing to severe disease were 1.24-fold (95% CI: 1.11-1.39) higher for Beta. Odds of progressing to critical disease were 1.49-fold (95% CI: 1.13-1.97) higher. Odds of COVID-19 death were 1.57-fold (95% CI: 1.03-2.43) higher." "" "" "" "Abu-Raddad" "2021" "https://doi.org/10.1101/2021.08.02.21261465" "doi:10.1101/2021.08.02.21261465" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 34 convalescent cases 4–9 weeks following infection in June 2020, before the emergence of B.1.1.7, neutralization titers against B.1.351 were, on average, 13.3-fold reduced compared with an early Victoria sample (p < 0.0001). Significantly, 18 of 34 samples failed to reach 50% neutralization at a plasma dilution of 1:20, with a number showing a near total reduction of neutralization activity. In 13 convalescent cases 4–9 weeks following infection with B.1.1.7, neutralization titers against B.1.351 were, on average, 3.1-fold reduced compared with an early Victoria sample (p < 0.0001)." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Testing against B.1.351 the 20 most effective mAbs (19 anti-RBD, 1 anti-NTD) from a screen of 377 against wild type, 4 of 20 antibodies had >10-fold fall in neutralization titers, with most of these showing a complete knockout of activity. This is in line with the key roles of K417, E484, and N501, in particular E484, in antibody recognition of the ACE2 interaction surface of the RBD. Regeneron mAb cocktail: The neutralization of REGN10987 was unaffected by B.1.351, while REGN10933 was severely impaired (773-fold). AstraZeneca mAb cocktail: Neutralization by the AZ pair of antibodies was little affected on B.1.351 compared with Victoria." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.351 defining mutations: Significant shift to infection in those without pre-existing conditions (79.6% vs 89% for non-VOC cases). Significant increase in hospitalization rate (19.3% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.3% vs 0.6% for non-VOC cases). PG: seems to be different notations around the LAL deletion, using the minimal shared definition to catch as many as possible." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The B.1.351 variant constellation causes an ∼20-fold increase in affinity for ACE2 compared with Wuhan RBD, which may influence transmissibility." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine plasma neutralization of B.1.351-spike virus was nominally robust but lower (~3x) than other variants of concern." "" "" "" "Liu" "2021" "https://doi.org/10.1056/NEJMc2102017" "doi:10.1056/NEJMc2102017" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "humoral response durability" "" "" "In a prospective study of 107 hospitalized patients, decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7 and P.1 variants for at least 6 months (last of two samples taken) in patients previously hospitalized for COVID-19. A weaker protection was however observed for the B.1.351 variant." "" "" "" "Betton" "2020" "https://doi.org/10.1093/cid/ciab308" "doi:10.1093/cid/ciab308" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Beta (B.1.351) has an IC50 fold change of 0.88x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using B.1.351 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~3-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~10 fold with L242del] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were signficiant, but >100x weaker than in previously infected patients after first dose." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, one third (5/15) of sera neutralized this B.1.351 pseudotype and only three had ID50 titers above 100. Only two of the 15 sera achieved 80% neutralization." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission." "" "" "" "Yinda" "2021" "https://doi.org/10.1101/2021.05.05.442780" "doi:10.1101/2021.05.05.442780" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Inoculation with the B.1.351 isolate resulted in lower clinical scores in 6 rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. Our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity." "" "" "" "Munster" "2021" "https://doi.org/10.1101/2021.05.07.443115" "doi:10.1101/2021.05.07.443115" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "4 health care workers in the 20's and 30's with no underlying conditions and seropositivity or confirmed 2020 SARS-CoV-2 infections were confirmed to have B.1.351 infection during a Februrary 2021 hospital outbreak in Luxembourg. Symptoms were mostly mild on first infection, and milder on second infection." "" "" "" "Staub" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.18.2100423" "doi:10.2807/1560-7917.ES.2021.26.18.2100423" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission." "" "" "" "Yinda" "2021" "https://doi.org/10.1101/2021.05.05.442780" "doi:10.1101/2021.05.05.442780" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer" "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.351 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the B.1.351 variants used, using the most popular as a stad in]" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In a Syrian hamster model, B.1.351 variant virus had >4x reduction in YRNT90 (measure of neutralization) using wild type convalescent sera. PG: Note that exact sequence for B.1.351 used was not disclosed." "" "" "" "Cochin" "2021" "https://doi.org/10.1101/2021.04.19.440435" "doi:10.1101/2021.04.19.440435" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "During an outbreak of SARS-CoV-2 501Y.V2 in a nursing home, all non-vaccinated residents (5/5) versus half of those fully vaccinated 2-5 weeks prior with BNT162b2 (13/26) were infected. Two of 13 vaccinated versus 4 of 5 non-vaccinated residents presented severe disease. BNT162b2 did not prevent the outbreak, but reduced transmission and disease severity. Among the 13 fully vaccinated residents who were infected, 2 (15.4%) presented with an asymptomatic disease, 9 (69.2%) developed mild to moderate symptoms, and 2 (15.4%) progressed to severe disease with fatal evolution secondary to acute respiratory distress syndrome (ARDS). There was no relationship between anti-S antibody levels at diagnosis and disease severity. Overall, the proportion of residents with severe disease in the non-vaccinated group (4/5) was higher than that in the vaccinated group (2/13). Only 1 vaccinated staff, but 10 unvaccinated were infected in the outbreak (no severe disease)." "" "" "" "Bailly" "2021" "https://doi.org/10.1093/cid/ciab446" "doi:10.1093/cid/ciab446" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer" "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v3 virus has reduced neutralization activity vs wild type: 42.4x (30 sera Pfizer median 9 days post 2nd dose) and 19.2x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.351 in 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.351 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0020 for moderate resistance." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.351 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. B.1.1.351 variant constellation ablates Class 3 N-terminal domain targeting antibodies COV2-2489 and COV2-2676 (the only two tested)." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine elicited antibodies neutralized virus with the B.1.351 spike protein had an average 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "VSV pseudotype B.1.351 entry mediated by the S proteins of the B.1.351 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.351 lineage effectiveness was observed as 16.9% (95% CI [10.4,23.0]) against infection, and 0% against severe/critical/fatal disease (95% CI [0-19.0]). Two weeks or more after 2nd dose, effectiveness climbed to 75.0% [70.5,78.9] against infection, and 100% against severe/critical/fatal disease (95% CI [73.7,100])." "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.351 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "VSV pseudotype B.1.351 showed 7.86-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections)." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype B.1.351 showed slight decrease in cell entry relative to wild type in 263T-ACE2 (kidney) cell line, and slight increase in Calu-3 (lung). Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abrogates Bamlanivimab, Etesevimab, or their combined use neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Approximately 6-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In one of eight cell lines tested (293T lung cells), a modest increase in cell entry was observed." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846" "T95I" "NC_045512.2:g.284C>T" "YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "65yo female with no severe Covid-19 risk factors tested positive 36 days after second dose of BNT162b2 (Pfizer) vaccine. Presented with fatigue, sinus congestion, and a headache developed; her symptoms plateaued and began to resolve six days later. [Mising genome coverage in regions of Spike covering clinically relevant mutations K417T, L452R, E484K, A701V, D796H, N501Y]" "" "" "" "Hacisuleyman" "2021" "https://doi.org/10.1056/NEJMoa2105000" "doi:10.1056/NEJMoa2105000" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22317,22319,22320,23399,23401,23402,23403" "T95I,D253G,D253G,D253G,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "B.1.526 (Iota) substantially increased IFR in older adults: by 46% (95% CI: 7.4 – 84%) among 45-64 year-olds, 82% (95% CI: 20 – 140%) among 65-74 year-olds, and 62% (95% CI: 45 – 80%) among 75+ during Nov 2020 – Apr 2021, compared to baseline IFR estimated for preexisting variants. [minimum clade defining mutations listed]" "" "" "" "Yang" "2021" "https://doi.org/10.1101/2021.08.04.21261596" "doi:10.1101/2021.08.04.21261596" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against B.1.621." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from vaccinees [ChAdOx1 and BNT162b2 primarily used in UK] shows decreased ability to neutralize B.1.621 compared to first wave virus and Alpha, with a magnitude of change similar to Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 69 test-positive were Mu. Two dose vaccine efficacy against Mu was 90.4% (73.9-96.5%), one dose VE was 45.8% (0.0-88.9%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Sera from individuals who have been infected with Delta does not have strong neutralising activity against B.1.621" "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 12.4x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. [This is a greater reduction than Beta @ 8.2x]" "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using live B.1.621 virus and a cytopathic effect-based assay, sera from 37 Pfizer/BioNTech BNT162b2 vaccinees collected 10-20 days post-booster showed significantly lower (95) but still ""robust"" neutralization than against ancestral B.1 virus (107)." "" "" "" "Messali" "2021" "https://doi.org/10.1002/jmv.27247" "doi:10.1002/jmv.27247" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 7.6x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. [This is a greater reduction than Beta @ 6.3x]" "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403" "T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 4.4-fold lower (95% CI: 4.3x-4.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403" "T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 1.5x-fold lower (95% CI: 0.05x-0.07x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,23012,23271,23399,23401,23402,23403,23604,23948" "T95I,E484K,A570D,D614G,D614G,D614G,D614G,P681H,D796H" "NC_045512.2:g.284C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2386G>C" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp796His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "51yo female with no severe COVID-19 risk factors tested positive 19 days after second dose of mRNA-1273 (Moderna) vaccine. Presented with sore throat, congestion, and headache developed; the next day she lost her sense of smell. Symptoms resolved over a one week period. Serum obtained 4 days after symptom onset was tested for neutralization against wild-type virus, the E484K mutant, and the B.1.526 variant. It was equally effective against each. These data suggest that the antibody response recognized these variants but was nonetheless insufficient to prevent a breakthrough infection. The virus detected matched neither B.1.1.7 nor B.1.526 VOC strains in wide circulation in New York at the time of infection, though shared some mutations." "" "" "" "Hacisuleyman" "2021" "https://doi.org/10.1056/NEJMoa2105000" "doi:10.1056/NEJMoa2105000" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,23399,23401,23402,23403" "T95I,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21855" "S98F" "NC_045512.2:g.293C>T" "YP_009724390.1:p.Ser98Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly enhanced the transduction rate in raccoon dog (Nyctereutes procyonoides) kidney (62.4%) and Rickett’s big-footed bat (Myotis pilosus) kidney (45.0%) cell cultures compared to epithelial-like human Huh-7 cells (38.9%)." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21929" "A123S" "NC_045512.2:g.367G>T" "YP_009724390.1:p.Ala123Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected in passage with mAb COV2-2489 during alanine mutagenesis antibody mapping experiment." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21969" "C136Y" "NC_045512.2:g.407G>A" "YP_009724390.1:p.Cys136Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massively decreases N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21969" "C136Y" "NC_045512.2:g.407G>A" "YP_009724390.1:p.Cys136Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected twice in passage with mAb COV2-2489." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. [PG: This mutation is adjacent to a well known deletion, which may confound the significance of this variant]" "" "" "" "Lucaci" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "These variants dominate in mink infections in North America, sometime supplemented with F486L. The Y453F variant found in other jurisdictions in mink infections is notably absent in North America." "" "" "" "" "2021" "https://doi.org/10.1101/2021.03.18.21253734v3" "doi:10.1101/2021.03.18.21253734v3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Kappa (B.1.617.1) shows 5.71x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Average 2x neutralization efficiency decrease against sera from 26 Phase II trial Covaxin (BBV152) vaccine recipents. Very similar to B.1.1.7 (~2x) in the same study, and the neutralization from 17 sera of natural infections across B1 lineages." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.04.23.441101" "doi:10.1101/2021.04.23.441101" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.1) showed a 1.12x increase in binding (KD) relative to D614G, but described as ""not significant"". [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cluster of B.1.617[.1] infections related to travel from India to USA, one patient with mild symptoms had received their second dose of Pfizer vaccine more than two weeks before the infection [i.e. vaccine breakthrough]." "" "" "" "Verghese" "2021" "https://doi.org/10.1128/JCM.00741-21" "doi:10.1128/JCM.00741-21" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617.1) showed a 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617.1) showed a 1.79x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~3.5x cleavage of S2 relative to WA1 (D614G) wildtype by Kappa (B.1.617.1) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~4.5x for closely related Delta B.1.617.2 also with P681R at the cleavage site)." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 (""Kappa"") reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Kappa (B.1.617.1) shows mean 1.97x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Kappa (B.1.617.1) has an IC50 fold change of 2.3x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Kappa (B.1.617.1) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Kappa (B.1.617.1) has an IC50 fold change of 80.2x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Kappa (B.1.617.1) has an IC50 fold change of 0.68x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.2 has an IC50 fold change of 0.04x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Omicron BA.2 has an IC50 fold change of 0.09x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.2 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Omicron BA.2 has an IC50 fold change of 0.08x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.2 has an IC50 fold change of 0.07x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Omicron BA.2 variant is 0.8x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.2 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21974" "D138Y" "NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.43 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21977" "P139S" "NC_045512.2:g.415C>T" "YP_009724390.1:p.Pro139Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected once in passage with mAb COV2-2676." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990" "Y145del,Y145del" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990" "Y145del,Y145del" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient." "" "" "" "McCarthy" "2021" "https://doi.org/10.1126/science.abf6950" "doi:10.1126/science.abf6950" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990,21993,21995,23012,23399,23401,23402,23403" "Y145del,Y145del,H146del,H146del,E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.436_438del,NC_045512.2:g.436_438del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.His146del,YP_009724390.1:p.His146del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Normalized for particle number, on ACE2.293T cells showed that the B.1.618 spike protein was about as infective as D614G wild type." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21993,21995" "H146del,H146del" "NC_045512.2:g.436_438del,NC_045512.2:g.436_438del" "YP_009724390.1:p.His146del,YP_009724390.1:p.His146del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient." "" "" "" "McCarthy" "2021" "https://doi.org/10.1126/science.abf6950" "doi:10.1126/science.abf6950" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21997,21998,21999,22000,22001" "K147E,K147E,K147E,K147E,K147E" "NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G" "YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21997,21998,21999,22000,22001" "K147E,K147E,K147E,K147E,K147E" "NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G" "YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21998" "H146Y" "NC_045512.2:g.436C>T" "YP_009724390.1:p.His146Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in 4A8 monoclonal antibody EC50 (i.e. ablated recognition), but much milder effect on mAbs within antigenic supersite ""i""" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22001" "K147Q" "NC_045512.2:g.439A>C" "YP_009724390.1:p.Lys147Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22002" "K147T" "NC_045512.2:g.440A>C" "YP_009724390.1:p.Lys147Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22002" "K147T" "NC_045512.2:g.440A>C" "YP_009724390.1:p.Lys147Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massively decreases N terminal domain antigen recognition by supersite i mAbs S2M28, S2X28, S2X333, 4A8 (but not S2L28)." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22003" "K147N" "NC_045512.2:g.441A>T" "YP_009724390.1:p.Lys147Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22005" "N148S" "NC_045512.2:g.443A>G" "YP_009724390.1:p.Asn148Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong positive selection (up to 72% of supernatant sequences) under six rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22010" "K150E" "NC_045512.2:g.448A>G" "YP_009724390.1:p.Lys150Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong positive selection (up to 40% of supernatant sequences) under three rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22010" "K150E" "NC_045512.2:g.448A>G" "YP_009724390.1:p.Lys150Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22011" "K150T" "NC_045512.2:g.449A>C" "YP_009724390.1:p.Lys150Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 22% of supernatant sequences) after COV47 convalescent plasma assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22011" "K150R" "NC_045512.2:g.449A>G" "YP_009724390.1:p.Lys150Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 18% of supernatant sequences) under two rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22016,22016" "W152R,W152R" "NC_045512.2:g.454T>A,NC_045512.2:g.454T>C" "YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For NTD-binding neutralizing antibody ADI-56479 this mutation causes a 1000x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22016,22016" "W152R,W152R" "NC_045512.2:g.454T>A,NC_045512.2:g.454T>C" "YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22018" "W152C" "NC_045512.2:g.456G>T" "YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Pseudoviruses carrying the W152C mutation demonstrated small increases in cell entry compared to D614G alone in 293T cells and human airway organoids." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22018" "W152C" "NC_045512.2:g.456G>T" "YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The W152C mutation reduced recognition of six NTD neutralizing mAbs, including a complete loss of binding for two of them, with a complementary pattern to that observed for S13I (also found in lineage B.1.427/B.1.429) out of 11 neutralizing mAbs evaluated." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022" "E154K" "NC_045512.2:g.460G>A" "YP_009724390.1:p.Glu154Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Approximately 2-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abrogates Bamlanivimab neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Significant decrease in combined Etesevimab+Bamlanivimab neutralization except at the highest concentration measured. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In two of eight cell lines tested (Caco-2 intenstinal and Calu-3 lung), a modest increase in cell entry was observed. This increase was not observed in a Calu-3 cell line with overexpressed ACE2. [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pfizer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~3x (compared to ~11x for B.1.351). [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22028,22034" "R158G,R158G" "NC_045512.2:g.467_472del,NC_045512.2:g.472A>G" "YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22033,23012,23604" "F157L,E484K,P681R" "NC_045512.2:g.471C>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.23.1-v2 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22033,23604" "F157L,P681R" "NC_045512.2:g.471C>A,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.23.1-v1 reduced 1.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22036" "R158S" "NC_045512.2:g.474A>T" "YP_009724390.1:p.Arg158Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected three times in passage with mAb COV2-2489." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:03." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type C*07:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DPB1*04:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*16:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*07:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22107,22111" "Q183H,Q183H" "NC_045512.2:g.549G>T,NC_045512.2:g.549G>T" "YP_009724390.1:p.Gln183His,YP_009724390.1:p.Gln183His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome" "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132" "R190S" "NC_045512.2:g.570G>T" "YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.69 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604" "R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in B.1.640.2 variant was ~1000x folds more significant in 8 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604" "R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1.640.2 variant was ~5.6x folds more significant in 9 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22188,23399,23401,23402,23403" "I210del,D614G,D614G,D614G,D614G" "NC_045512.2:g.629_631del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "A 42yo Iranian male was reinfected with B.1.36 lineage virus 128 days after infection with genetically distinct B.1.36 virus, with negative PCR tests in between. In the first instance patient presented with cough, headache, severe diarrhea. In the second instance symptoms were more severe: body pain, shortness of breath, headache and anosmia. Anti-SARS-CoV-2 IgG and IgM tests were negative after both episodes. [Non-seroconversion may be associated with elevated risk of re-infection] [I210del is a homoplasy that has appeared in several disparate parts of the global phylogenetic tree, including A and B lineages, primarily in LMICs]" "" "" "" "Salehi-Vaziri" "2021" "https://doi.org/10.1016/j.virusres.2021.198421" "doi:10.1016/j.virusres.2021.198421" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:01." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*13:02." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:02." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.98 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227" "A222V,A222V" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227,23399,23401,23402,23403" "A222V,A222V,D614G,D614G,D614G,D614G" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "humoral response durability" "" "" "27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3), i.e. with a 9 month interval. Both cases were mild. No significant differences in the neutralizing capacity of the two lineages were observed in 4 sera taken (1 pre-reinfection, three post-reinfection). Neutralizing antibody titres (IC50) before and immediately after re-infection were <300 against both strains, and jumped >7x upon re-infection. Viral titres were also higher in the second case. Second case also includes N:p.A220V" "" "" "" "Brehm" "2021" "https://doi.org/10.3390/v13040661" "doi:10.3390/v13040661" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227,23399,23401,23402,23403" "A222V,A222V,D614G,D614G,D614G,D614G" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3). Both cases were mild. Second case also includes N:p.A220V" "" "" "" "Brehm" "2021" "https://doi.org/10.3390/v13040661" "doi:10.3390/v13040661" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22293" "L244S" "NC_045512.2:g.731T>C" "YP_009724390.1:p.Leu244Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22301" "S247R" "NC_045512.2:g.739A>C" "YP_009724390.1:p.Ser247Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22304" "Y248H" "NC_045512.2:g.742T>C" "YP_009724390.1:p.Tyr248His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22314" "P251L" "NC_045512.2:g.752C>T" "YP_009724390.1:p.Pro251Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317" "G252D" "NC_045512.2:g.755G>A" "YP_009724390.1:p.Gly252Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317,22319,22320" "D253G,D253G,D253G" "NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317,22319,22320" "D253G,D253G,D253G" "NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22319" "D253Y" "NC_045512.2:g.757G>T" "YP_009724390.1:p.Asp253Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite ""i"", but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22323" "S254Y" "NC_045512.2:g.761C>A" "YP_009724390.1:p.Ser254Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22323" "S254F" "NC_045512.2:g.761C>T" "YP_009724390.1:p.Ser254Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite ""i"" monoclonal antibodies." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22326" "S255F" "NC_045512.2:g.764C>T" "YP_009724390.1:p.Ser255Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22328,22329,22331" "G257S,G257S,G257S" "NC_045512.2:g.769G>A,NC_045512.2:g.769G>A,NC_045512.2:g.769G>A" "YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334" "W258R" "NC_045512.2:g.772T>C" "YP_009724390.1:p.Trp258Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334" "W258R" "NC_045512.2:g.772T>C" "YP_009724390.1:p.Trp258Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334,22879,22881,22882,22882,22904,22910,23012" "W258R,N440K,N440K,N440K,N440K,N450D,N450D,E484K" "NC_045512.2:g.772T>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22340" "A260T" "NC_045512.2:g.778G>A" "YP_009724390.1:p.Ala260Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22344" "G261D" "NC_045512.2:g.782G>A" "YP_009724390.1:p.Gly261Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Multiple mink but no humans on one farm in Denmark, potential adaptation." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22377" "P272L" "NC_045512.2:g.815C>T" "YP_009724390.1:p.Pro272Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*02:01." "" "" "" "Dolton" "2021" "https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf" "doi:10.1101/2021.06.21.21259010v2.full.pdf" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22377" "P272L" "NC_045512.2:g.815C>T" "YP_009724390.1:p.Pro272Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*08:01." "" "" "" "Dolton" "2021" "https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf" "doi:10.1101/2021.06.21.21259010v2.full.pdf" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 1.2x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.3 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22583" "V341I" "NC_045512.2:g.1021G>A" "YP_009724390.1:p.Val341Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22599" "R346T,R346T,R346T,R346T" "NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22599" "R346T,R346T,R346T,R346T" "NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22599,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22939,22942,22942,22992,23009,23010,23012,23013,23027,23029,23030,23031,23053,23054,23055,22992,22995,23060,23061,23062,23063,23071,23074,23075" "R346T,R346T,R346T,R346T,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N460K,N460K,N460K,S477N,E484A,E484A,E484A,E484A,F490S,F490S,F490S,F490S,Q498R,Q498R,Q498R,T478K,T478K,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H" "NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The hACE2-binding affinity of XBB.1.5 RBD has a dissociation constant KD of 3.4 nM, where S486P is the distinguishing Spike mutation vs parent XBB.1 RBD with a much weaker KD (19 nM), as measured by surface plasmon resonance (SPR) assays." "" "" "" "Yue" "2023" "https://doi.org/10.1101/2023.01.03.522427" "doi:10.1101/2023.01.03.522427" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346K,R346K" "NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346I,R346I" "NC_045512.2:g.1037G>T,NC_045512.2:g.1037G>T" "YP_009724390.1:p.Arg346Ile,YP_009724390.1:p.Arg346Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Provides ~80% escape from mAb COV2-2130, even though its appearance in culture is formed without selective mAb pressure." "" "" "" "Dong" "2021" "https://doi.org/10.1101/2021.01.27.428529" "doi:10.1101/2021.01.27.428529" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346K,R346K" "NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation, which has emerged in some Omicron sequences, has a 0.7x reduction in neutralization activity with Sotrovimab in a VSV model on Vero E6 cells. [Omicron sequences with R346K may very well have a non-additive neutralization rather than 2.7x+0.7x = 3.4x]" "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346K,R346K" "NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 53% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 2/3 antibody C603." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 2/3 antibody C603." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 30% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22622" "N354D" "NC_045512.2:g.1060A>G" "YP_009724390.1:p.Asn354Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.13 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22624" "N354K" "NC_045512.2:g.1062C>A" "YP_009724390.1:p.Asn354Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22627,22629" "K356T,K356T" "NC_045512.2:g.1067A>C,NC_045512.2:g.1067A>C" "YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.14 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22629" "K356R" "NC_045512.2:g.1067A>G" "YP_009724390.1:p.Lys356Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22632" "R357K" "NC_045512.2:g.1070G>A" "YP_009724390.1:p.Arg357Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.18 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as ""stabilizing"" since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.72 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as ""stabilizing"" since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22661" "V367I" "NC_045512.2:g.1099G>A" "YP_009724390.1:p.Val367Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22679" "S373P" "NC_045512.2:g.1117T>C" "YP_009724390.1:p.Ser373Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Reduce affinity for mildly cross-reactive CR3022 (2003 pandemic SARS monoclonal antibody cross-reactive to SARS-CoV-2)" "" "" "" "Long" "2020" "https://doi.org/10.1128/mBio.02707-20" "doi:10.1128/mBio.02707-20" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22679,23009,23010,23012,23013" "S373P,E484A,E484A,E484A,E484A" "NC_045512.2:g.1117T>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "On December 7, 2021 the estimate of Omicron effective reproduction rate (Rt) is 3.12 [presumably R0 is higher], compared to 1.12 for the dominant Delta VOC at that time. [shorthand of variant list shraed by all contemporary BA lineage used here]" "" "" "" "" "2021" "https://doi.org/10.47326/ocsat.dashboard.2021.1.0" "doi:10.47326/ocsat.dashboard.2021.1.0" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22686" "S375F" "NC_045512.2:g.1124C>T" "YP_009724390.1:p.Ser375Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch." "" "" "" "Lucaci" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22696" "K378N" "NC_045512.2:g.1134G>T" "YP_009724390.1:p.Lys378Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for mildly neutralizing COV2-2677 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23402,23403" "P384L,D614G,D614G,D614G,D614G" "NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23402,23403" "P384L,D614G,D614G,D614G,D614G" "NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23402,23403" "P384L,D614G,D614G,D614G,D614G" "NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22745" "V395I" "NC_045512.2:g.1183G>A" "YP_009724390.1:p.Val395Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22766" "I402V" "NC_045512.2:g.1204A>G" "YP_009724390.1:p.Ile402Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22783,22784,22785,22786,22786" "R408S,R408S,R408S,R408S,R408S" "NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C" "YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22783,22784,22785,22786,22786,23009,23010,23012,23013,23060,23061,23062,23063" "R408S,R408S,R408S,R408S,R408S,E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a study of 481 vaccinees going from lowest to highest infection rate, 2 doses of CoronaVac and 1 dose of BNT162b2 had the lowest infection rate at 6.3%, then it was 3 doses of BNT162b2 having a infection rate of 16.6%. 2 and 3 doses of CoronaVac had 48.6% and 20.6% infection rate respectively. 2 doses of BNT162b2 has the highest infection rate at 49.2%." "" "" "" "Zhou" "2022" "https://doi.org/10.1101/2022.05.09.491254" "doi:10.1101/2022.05.09.491254" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates binding by RBD-directed mAbs CB6 and 910-30 (targeting the inner side of the RBD). Pseudotyped virus model impairs binding by RBD-directed mAbs 4-20 and REGN10933." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "1.1 fold drop in IC50 of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The K417N mutation decreased the affinity ~4 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs)" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs)" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C682, and to a lesser extent C614 and C660" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against IgG1 monoclonal antibody ab1." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.86 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~6x binding against this isolated mutation. Estesevimab lost ~100x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 7.5 fold decrease in KD value for antibody binding of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 1.5 fold decrease in KD value of antibody binding of ACE2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 3-fold decrease in affinity compared to wild-type RBD on the cell surface (Kd = 145.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection, Two-tailed Wilcoxon matched-pairs signed-rank test shows mild resistance P=0.0361." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 36.9 fold decrease in KD value for antibody binding of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "27% of 44 early pandemic exposure convalescent plasma/sera lose all activity against a RBD triple mutant pseudovirus (RBD mutatants of the 501Y.V2 ""South African"" lineage), while only 23% retained high titres" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 (""South African"") lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 (""South African"") lineage background" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of the B.1.351 RBD variants for ACE2 increased by 3.7 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.4-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.351 key variants lentivirus. Compare to 8.8-fold reduction against cultured B.1.351 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from B.1.351." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26)." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26)." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.351 and P.1 samples showed average Ct cycle threshold of 22.2 vs 23 for wildtype (i.e. ~60% higher viral load) comparing 3360 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibodies ab8 and IgG1 ab1. Complete loss for the same antibodies was also observed against S1 pseudotyped and full Spike protein trimers with both B.1.351 and P.1 lineage variants, with slight binding signal for P.1 against IgG1 at the highest concentration tested (1uM). Complete loss of neutralization by these two antibodies was also observed." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This combination showed ~3x increase binding to ACE2 vs wild type, about half that of the B.1.1.7 lineage, suggesting that the K417N mutation is slightly detrimental to ACE2 binding, probably as a result of disrupting the salt bridge formed with ACE2 residue D30" "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Moderna vaccinee sera, 2.7x reduction in neutralization, and 6.4 for the full B.1.351 Spike mutation complement, but despite the observed decreases, titers in human vaccinee sera against the B.1.351 variant remained at clinically significant level of ~1/300." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.01.25.427948" "doi:10.1101/2021.01.25.427948" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "36,590 variant-specific RT-PCR tests were performed on samples collected between April 12 and May 7, 2021 in France to compare variant spread. Compared to January to March 2021, B.1.351 variant had a significant transmission advantage over B.1.1.7 in some regions (15.1 to 16.1% in Île-de-France and 16.1 to 18.8% in Hauts-de-France). This shift in transmission advantage is consistent with the immune evasion abilities of B.1.351 and the high levels of immunization in these regions." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.05.12.21257130" "doi:10.1101/2021.05.12.21257130" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure." "" "" "" "Pearson" "2021" "https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant of key B.1.351 lineage mutations showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure." "" "" "" "Pearson" "2021" "https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Average ~10-fold reduction in neutralization efficacy in convalescent sera of 16 health workers infected in Spring 2020." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) with enrollment June 24 and November 9, 2020 from ~2000 HIV-negative 18-64 year olds (1:1 placebo to treatment), incidence of serious adverse events 14 or more days post- 2nd dose was balanced between the vaccine and placebo groups. A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed 3.5x reduction in neutralization (ID50) for B.1.351 RBD pseudotype HIB-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a similar 3.2x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 2 (B.1.351) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolished neutralization by mAbs CQ026 and CQ038, greatly diminished neutralization by CQ012 and CQ046." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23041,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trachea viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~750x fold drop in the R3P1-E4 antibody in comparison to the IgG control." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23041,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Lung viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~2266x fold drop in the R3P1-E4 antibody in comparison to the IgG control." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23041,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "100% of the 5 8‑month‑old male R3P1-E4 antibody treated mice suvived 14 days after infection while only 60% the control group mice survived 5 days post infection." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~5x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied]" "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (no synergy as level approx. that of N501Y alone)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 57.1 fold decrease in KD value for antibody binding of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.64 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 1.1 fold decrease in KD value of antibody binding of ACE2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.25 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 antibody C682" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The K417T mutation decreased the affinity ~2 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~16x binding against this isolated mutation. Estesevimab lost ~16x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 2.9 fold decrease in KD value for antibody binding of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "2.6 fold increase in IC50 of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,23012,23060,23061,23062,23063" "K417T,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from P.1." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,23012,23060,23061,23062,23063" "K417T,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of the P.1 RBD variants for ACE2 increased by 5.3 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The KD for the pseudotyped P.1-ACE2 interaction is 4.8 nM, showing that binding to P.1 is essentially indistinguishable from B.1.351 (4.0 nM), which binds with ~19x greater affinity that wild type." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22851" "T430I" "NC_045512.2:g.1289C>T" "YP_009724390.1:p.Thr430Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22865" "A435S" "NC_045512.2:g.1303G>T" "YP_009724390.1:p.Ala435Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb H014 (on D614G background)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The N440K variant produced ten times higher infectious viral titers than a prevalent A2a strain, and over 1000 folds higher titers than a much less prevalent A3i strain prototype in Caco2 cells. Interestingly, A3i strain showed the highest viral RNA levels, but the lowest infectious titers in the culture supernatants, indicating the absence of correlation between the RNA content and the infectivity of the sample." "" "" "" "Tandel" "2021" "https://doi.org/10.1101/2021.04.30.441434" "doi:10.1101/2021.04.30.441434" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 0.7x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "N501Y substitution decreased the neutralizing and binding activities of CB6 and increased that of BD-23" "" "" "" "Cheng" "2021" "https://doi.org/10.1186/s12985-021-01554-8" "doi:10.1186/s12985-021-01554-8" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 45% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, eliminated in subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 3 antibody C669 mildly selected for the emergence of the N440K mutation in vitro (in contrast to N440H which caused mild escape in Class 1/2 mAb C653)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882,23399,23401,23402,23403" "N440K,N440K,N440K,N440K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "A 47yo Indian male was reinfected with B.1.36 lineage virus in September 2020 after infection with genetically distinct B.1.36 virus in July, with negative PCR tests in between. While the forst episode was asymptomatic, the second included fever, cough, and malaise. The second case additionally contained stopgain ORF3a:E261*" "" "" "" "Rani" "2021" "https://doi.org/10.1002/jmv.26997" "doi:10.1002/jmv.26997" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444T" "NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444R" "NC_045512.2:g.1331A>G" "YP_009724390.1:p.Lys444Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Identified in 6/20 replicates of recombinant VSV growth in the presence of mAb COV2-2130." "" "" "" "Dong" "2021" "https://doi.org/10.1101/2021.01.27.428529" "doi:10.1101/2021.01.27.428529" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444T" "NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Results in 3.7-fold drop in neutralization potency for COVA2-29, which is a cluster I RBD141 specific antibody." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444R" "NC_045512.2:g.1331A>G" "YP_009724390.1:p.Lys444Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 20% of supernatant sequences) under two rounds of COV-NY convalescent plasma passage, eliminated in rounds three and four" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444T" "NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolishes binding efficiency vs wild type for mAb REGN10933." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 14% of supernatant sequences) after COV-NY convalescent plasma assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Improvement in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-01 and moderately resistant to 2H04 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22896" "V445A" "NC_045512.2:g.1334T>C" "YP_009724390.1:p.Val445Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 41% appearance in 2 passages against Regeneron monoclonal antibody RGN10987 @ 10ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2499 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 1 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed a ~4x drop in sensitivity." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-02, SARS2-32 and SARS2-35 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Decrease in neutralization capability of all 4 convalescent sera tested (1 ablated)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations), triple replicates. Against a broader panel of 16 convalescent plasma (no replicates), reductions in neutralization are considerably less dramatic in pattern, and sometime neutralization increases." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 95% appearance in 2 passages against Regeneron monoclonal antibody RGN10934 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 4 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Most effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-07 nd moderately resistant to SARS2-16 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910,23012,23039,23040,23373,25046" "N450D,N450D,E484K,Q493R,Q493R,T604I,P1162S" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1811C>T,NC_045512.2:g.3484C>T" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Thr604Ile,YP_009724390.1:p.Pro1162Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22905" "N448S" "NC_045512.2:g.1343A>G" "YP_009724390.1:p.Asn448Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22907" "Y449H" "NC_045512.2:g.1345T>C" "YP_009724390.1:p.Tyr449His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22907" "Y449N" "NC_045512.2:g.1345T>A" "YP_009724390.1:p.Tyr449Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912,22916" "L452M,L452M" "NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A" "YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912,22916" "L452M,L452M" "NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A" "YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.67 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Observed ~2x decrease on average in neutralization efficacy in convalescent sera of 16 health workers." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 3 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2/3 antibody C628 and class 2 antibody C643 selected for the emergence of the L452R mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Ablation of neutralization capability of 3 of 4 convalescent sera tested, the other is significantly hindered." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~1.7-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "10 of 14 RBD-specific mAbs that showed at least 10-fold reduced neutralization of B.1.427/B.1.429 variant pseudotype (S13I, W152C, and L452R) were also found to poorly bind to just a L452R RBD mutant, demonstrating a role for this mutation as an escape mechanism for certain RBD-targeting mAbs." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "L452R derivative virus did not induce IFN-gamma expression even at the highest concentration tested (10 nM) in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456)." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We observed increased entry by pseudoviruses carrying the L452R mutation compared to D614G alone, with a 6.7 to 22.5-fold increase in 293T cells and a 5.8 to 14.7-fold increase in human airway organoids." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.32 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02." "" "" "" "Motozono" "2021" "https://doi.org/10.1016/j.chom.2021.06.006" "doi:10.1016/j.chom.2021.06.006" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs X593 and P2B-2F6" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. [listed as L454R in Figure, but L452R in text, also text suggests not statistically significant, but error bars say otherwise in Figure 4]" "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. L452R conferred about a two-fold reduction in neutralisation by vaccine sera, but was not statistically significant with this sample size." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~5x binding against this isolated mutation. Cligavimab lost ~4x binding against this isolated mutation. Regdanvimab lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-02 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Increased stability of RBD expression in yeast, suggesting increased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012" "L452R,L452R,L452R,E484K" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant combination shows a ~4-5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, same as L452R alone." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012" "L452R,L452R,L452R,E484Q" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484Q had a ~5x drop in neutralization (vs ~10x for E484K). When E484Q and L452R were combined, the fold change was significant, but similar to that of L452R alone (~2x), suggesting no evidence for an additive effect [perhaps even E484Q effect dilution]." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617) showed a 1.22x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2.5x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617) showed a 1.30x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.18x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x drop in neutralization (NT50) [working with the delins, less than just L452R but more than just E484Q]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x infectivity advantage to the spike particles [less than L452R or E484Q alone working with the delins]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Pseudotyped viruses for B.1.617 was 2.3-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. [details on the convalescent patient sera collection are not abundantly clear in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617) showed a 1.85x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The combination caused a 3-fold increase in infectivity relative to D614G wild type. [compare to 3.5x for L452R alone]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604" "L452R,L452R,L452R,E484Q,P681R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Gross examination of 3+3 hamster lung specimens showed pronounced congestion and hemorrhages on days 5 and 7 post-infection in the case of the B.1.617.1 as compared with the B.1. The lung lesions with the B.1 variant were minimal to mild whereas with B.1.617.1 they were moderate. For B.1 pneumonic changes were minimal to mild (inflammatory cell infiltration, focal consolidation and mild congestion). The pronounced changes (moderate to severe) with mononuclear infiltration in the alveolar interstitial space, interstitial septal thickening, consolidation and pneumocyte hyperplasia were observed with B.1.617.1 variant consistently." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.05.05.442760" "doi:10.1101/2021.05.05.442760" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604" "L452R,L452R,L452R,E484Q,P681R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In 9 infected hamsters each for B.1 and B.1.617.1, no significant change in viral load or subgenomic RNA levels were detected." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.05.05.442760" "doi:10.1101/2021.05.05.442760" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604" "L452R,L452R,L452R,E484K,P681R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant combination shows a ~3x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, significantly less of a decrease than any B.1.617 lineage variants alone, suggesting a synergistic effect on cell entry while maintaining known immunity esacpe mutants." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,P681R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Normalized for particle number, on ACE2.293T cells showed that the B.1.617 spike protein was >2-fold increase in infectivity relative to D614G wild type." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23060,23061,23062,23063" "L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of these B.1.417/B.1.429 defining variants in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The L452R mutation increased the infectivity more than two-fold in these conditions." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 7.42x drop in neutralization (NT50) [mostly from 3 of the sera]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this RBD mutation conferred a 2.36x drop in neutralization (NT50)." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~2x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 583 test-positive were Epsilon. Two dose vaccine efficacy against Epsilon was 97.6 (90.2-99.4%), one dose VE was 76.3 (48.1-89.1%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917" "L452Q" "NC_045512.2:g.1355T>A" "YP_009724390.1:p.Leu452Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917" "L452Q" "NC_045512.2:g.1355T>A" "YP_009724390.1:p.Leu452Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.27 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 3.4x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.038x fold change in IC50 in C.37 Lambda" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 1.7x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.048x fold change in IC50 in C.37 Lambda" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "VSV pseudotyped with Y453F reduced inhibition by most of the 13 potent convalescent serum/plasma samples tested, albeit with variable efficiency (median increase of serum/plasma titer required for 50% neutralization [NT50] = 1.62x, range = 1.02x to 3.43x), indicating that this RBD mutation may compromise SARS-CoV-2 control by preexisting neutralizing antibody responses." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.celrep.2021.109017" "doi:10.1016/j.celrep.2021.109017" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.25 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "10-fold reduction in binding efficiency vs wild type for MAb REGN10933." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~12x binding against this double mutation. Casirivimab lost ~64x binding against this double mutation. Cligavimab lost ~6x binding against this double mutation. Estesevimab lost ~10x binding against this double mutation. Imdevimab lost ~5x binding against this double mutation. Regdanvimab lost ~8x binding against this double mutation. Sotrovimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed in 4 separate mink farms in Denmark, and Y453F is circulating relatively widely in humans." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02." "" "" "" "Motozono" "2021" "https://doi.org/10.1016/j.chom.2021.06.006" "doi:10.1016/j.chom.2021.06.006" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "The induction level of IFN-gamma expression by the Y453F derivative in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456) was significantly lower." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "" "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Casirivimab lost >50x binding against this mutation." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.celrep.2021.109017" "doi:10.1016/j.celrep.2021.109017" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "Y453F,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.1358A>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "The so-called ""delta F"" variant combination previously observed in mink spillover events also emerged in a lymphoma patient (non-Hodgkin diffuse B-cell lymphoma IV stage B) with a long-term COVID-19 infection (4 months) where 18 de novo mutation occureed overall. Patient was taking rituximab, the B-cell-depleting agent, and had no detectable neutralizing antibody response." "" "" "" "Bazykin" "2021" "https://virological.org/t/emergence-of-y453f-and-69-70hv-mutations-in-a-lymphoma-patient-with-long-term-covid-19/580" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22924,22925,22926" "L455S,L455S,L455S" "NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C" "YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.45 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22926,22927,22927,22928,22930,22930" "F456L,F456L,F456L,F456L,F456L,F456L" "NC_045512.2:g.1366T>C,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>A,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>G,NC_045512.2:g.1368T>A" "YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This double substitution reduces neutralization by RBD-specific mAbs from different clusters, specifically, the cluster I mAb COVA2-29, cluster III mAb COVA2-07 and cluster VI mAb COVA1-12. For COVA1-12 all neutralization activity is abolished, while COVA2-07 activity is just below the level required to calculate an IC50 value." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Moderate in vitro selection against class 1 (Spike 'up' conformation) antibodies C683 and C664. Unclassified antibody C666 selected for the emergence of the F456V mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22936" "K458N" "NC_045512.2:g.1374G>T" "YP_009724390.1:p.Lys458Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.09 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460Y" "NC_045512.2:g.1378A>T" "YP_009724390.1:p.Asn460Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mild escape mutant emergent for class 1 antibody C613 in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22941" "N460I" "NC_045512.2:g.1379A>T" "YP_009724390.1:p.Asn460Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22941" "N460S" "NC_045512.2:g.1379A>G" "YP_009724390.1:p.Asn460Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22964" "I468V" "NC_045512.2:g.1402A>G" "YP_009724390.1:p.Ile468Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22964" "I468V" "NC_045512.2:g.1402A>G" "YP_009724390.1:p.Ile468Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22976" "I472V" "NC_045512.2:g.1414A>G" "YP_009724390.1:p.Ile472Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22976" "I472V" "NC_045512.2:g.1414A>G" "YP_009724390.1:p.Ile472Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb X593 (on D614G background)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C102, C105 and C144 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~50x binding against this isolated mutation. Estesevimab lost ~8x binding against this isolated mutation. Sotrovimab lost ~30x binding against this isolated mutation. Tixagevimab lost ~15x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some class 1 (Spike 'up' conformation) antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 host variant dependency" "" "" "This mutation's measured interaction affinity with ACE2:p.S19P (0.03% minor allele frequency, found almost exclusively in African/African-Americans in the GnomAD database) was significantly lower than the predicted value, indicating that these mutations were not independent. This is consistent with the fact that the ACE2 residue S19 is adjacent to RBD residue S477 in the contact interface." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 2.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "While S477N itself is highly resistent to a broad range of monoclonal antibodies, combined with S514F high neutralization is restricted to only three antibodies in a broad screen." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of mild positive and negative changes in neutralization capability of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), 10 show low neutralization." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 11 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.22 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-07, SARS2-16 and SARS2-19 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility." "" "" "" "Singh" "2021" "https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows some resistence across all antibodies tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility." "" "" "" "Singh" "2021" "https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding, with increasing proportion in subsequent rounds." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-07 and SARS2-16 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,22995,23042" "T478K,T478K,S494P" "NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1480T>C" "YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Combination of RBD mutations appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome complicated by diffuse alveolar hemorrhage, who was receiving anticoagulation therapy, glucocorticoids, cyclophosphamide, and intermittent rituximab and eculizumab." "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23012" "S477N,E484K" "NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~10x binding against this double mutation. Tixagevimab lost ~16x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was neutralized slightly less than D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Compared to the clade 20A strains that predominated during phase 1 between March and May 2020, the Marseille-4 variant (characterized by this mutation plus N:p.M234I;A376T) was associated with a lower frequency of cough, rhinitis, and olfactory and gustatory disorders. By contrast, hypoxemia was more frequent in patients infected with the Marseille-4 variant." "" "" "" "Fournier" "2021" "https://doi.org/10.1016/j.ijid.2021.03.068" "doi:10.1016/j.ijid.2021.03.068" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "11 cases of re-infection with the ""Marseille-4"" variant found within 1028 positive tests, where all of the earlier infections were from different strains. This lineage is also characterized by N:p.M234I;A376T" "" "" "" "Fournier" "2021" "https://doi.org/10.1016/j.ijid.2021.03.068" "doi:10.1016/j.ijid.2021.03.068" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23003" "N481Y" "NC_045512.2:g.1441A>T" "YP_009724390.1:p.Asn481Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Minor variant in initial round of in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009" "V483L" "NC_045512.2:g.1447G>C" "YP_009724390.1:p.Val483Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, 1B07, SARS2-32, SARS2-35 and SARS2-07 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" """E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels""" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in all 4 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Remarkably, several of the E484 escape mutants were resistant to neutralization at the highest concentration (1:80 initial dilution) of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), all but one show major resistance." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 152 virus from a chronically infected patient: although mAb C1A-B12 had no activity against this pseudotype, all three affinity optimized versions were active; the antibody containing the most mutations, C1A-B12.3, was the most potent (IC50 <0.5 μg/mL)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 152 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 152 S pseudotype was resistant to neutralization." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This Spike pseudotype for Day 152 virus from a chronically infected patient was completely resistent to REGN10933." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous." "" "" "" "Braeye" "2022" "https://doi.org/10.1101/2022.05.09.22274623" "doi:10.1101/2022.05.09.22274623" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "3rd exposure to antigen by Delta (B.1.617.2) (n=24) breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a 3rd mRNA vaccine dose in individuals aged 21 –63 years, median age=30 years. Data collected 5.5 months after 2nd vaccination." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous." "" "" "" "Braeye" "2022" "https://doi.org/10.1101/2022.05.09.22274623" "doi:10.1101/2022.05.09.22274623" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In sera from 17 sero-positive blood donors, and 18 months post-infection (May 2020) sera from 17 health care workers in Sweden, a 40x drop in neutralization by Omicron (B.1.1.529) pseudotyped lentivirus was observed in HEK293T cells using the First WHO International Standard (20/136). Median IC50 reduction was ~6x for the blood donors, and ~4.5x for the health care workers." "" "" "" "Sheward" "2021" "https://drive.google.com/file/d/1CuxmNYj5cpIuxWXhjjVmuDqntxXwlfXQ/view" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23071,23074,23075,22992,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,Y505H,Y505H,Y505H,S477N,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1430G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using molecular dynamics simulation, ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations." "" "" "" "Zhang" "2022" "https://doi.org/10.1101/2022.06.05.493249" "doi:10.1101/2022.06.05.493249" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "The only mutation in the B.1.351 lineage that appears to contribute to neutralization reduction (~1.7x across 10 convalescent sera from April 2020 infectees)" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 15/20 convalescent sera was significantly lower against this pseudotyped virus model" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2 antibodies C627, C602, C671, C643, and class 2/3 antibody C603 selected for the emergence of the E484K mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 ""New York"" lineage, lentivirus pseudotyped with this mutation combination in showed 3.3x reduction in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers of non-human primate sera after one or two doses of Ad26.COV2.S (Jannsen vaccine) against the variants containing the E484K substitution in the RBD were present but reduced (fold reduction between 3.35–7.78, 95% confidence interval all above twofold difference, one-sample t test)." "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-02, 1B07, SARS2-16, SARS2-32, SARS2-35 and 2B04 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Multiple individuals in two related households were infected with a newly acquired E484K mutation within the B.1.311 lineage. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient's quarantine period." "" "" "" "Sabin" "2021" "https://doi.org/10.1101/2021.10.02.21264415" "doi:10.1101/2021.10.02.21264415" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Of 50 mAbs tested, major loss of neutralization observed for S2N28, S2X615, S2N12, S2X192, S2H7, S2X16, S2X58, S2H70, S2X613, S2D19, S2N22, S2D32, S2H58, S2M11, S2D106, S2X30." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Monoclonal antibodies 13G9 and 58G6 maintain fairly high neutralization potency, compared to others interfacing with E484K." "" "" "" "Li" "2021" "https://doi.org/10.1101/2021.04.19.440481" "doi:10.1101/2021.04.19.440481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Analyzing responses to the E484K mutation seen in B.1.351 and P.1 variants, we noted that it did not fall in a region predicted to bind the HLAII alleles tested (table S4). The mutation appeared to have no substantial or differential impact on T cell responses." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Human sera from 5 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) neutralized this variant 3.4x less relative to reference USA-WA1/2020 strain. 8 convalescent plasma with weak IgG ELISA titre neutralized this variant 2.4x less relative to reference USA-WA1/2020 strain. One plasma failed to neutralize at all. 11 convalescent plasma with moderate IgG ELISA titre neutralized this variant 4.2x less relative to reference USA-WA1/2020 strain. 11 convalescent plasma with high IgG ELISA titre neutralized this variant 2.6x less relative to reference USA-WA1/2020 strain." "" "" "" "Jangra" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~20x binding against this isolated mutation. Casirivimab lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484K conferred a ten-fold reduction in neutralisation by vaccine sera." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~16x binding against this isolated mutation. Casirivimab lost ~16x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 3 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, E484Q shows a notably resistant profile, comparable to or even more resistant than E484K at later time points (i.e. more resistant to immune cell somatic mutation evolution), see Figure 5a,b. Subject C 32 days post-infection showed >>10 fold reduction in neutralization, reducing to ~10-fold by day 104. Subject B 26 days post-infection showed ~10 fold reduction in neutralization, reducing to ~4x at day 113. Notably, Subject B also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 32, and no E484K immune escape at day 104. Subject I 26 days post-infection showed ~10 fold reduction in neutralization, with no reduction in escape at day 102. Notably, Subject I also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 26, and no E484K immune escape at day 102." "" "" "" "Greaney" "2021" "https://doi.org/10.1016/j.chom.2021.02.003" "doi:10.1016/j.chom.2021.02.003" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in all 4 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Individual variants appearing at <=30% frequency at day 21 in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then appearing all at >95% frequency at day 27." "" "" "" "Chen" "2021" "https://doi.org/10.1101/2021.04.08.21254791" "doi:10.1101/2021.04.08.21254791" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.6 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported moderate increase in affinity compared to wild-type RBD on the cell surface (Kd = 38.5nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "E484K pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed a mean 2.8x decrease in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">20% (ELISA significance threshold) drop in antibody binding by this variant against monoclonal antibody VH-Fc ab8." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a 10x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus)" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody VH-Fc ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus)" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, ELISA tests show 10x reduced efficacy of a majority of isolated antibodies, but only a modest decrease for vaccine plasma overall." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "As measured by surface plasmon resonance, RBD with the E484K mutation alone showed a mean 19.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "This mutation occurred in 100% of sequenced virions after 12 passages and led to a 4-fold decrease in convalescent plasma neutralization activity" "" "" "" "Andreano" "2020" "https://doi.org/10.1101/2020.12.28.424451" "doi:10.1101/2020.12.28.424451" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in binding efficiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape due to E484K [given Dec 2020-Apr 2021 time frame of the study, this is assumed to entail both Beta and Gamma lineages]." "" "" "" "Chung" "2021" "https://doi.org/10.1136/bmj.n1943" "doi:10.1136/bmj.n1943" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22597,22599" "E484K,R346K,R346K" "NC_045512.2:g.1450G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E484K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22810,22811,22812,22813,22813" "E484K,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~32x binding against this double mutation. COR-101 lost ~160x binding against this double mutation. Casirivimab lost ~16x binding against this double mutation. Estesevimab lost ~32x binding against this double mutation. Regdanvimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~13x more infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22810,22811,22812,22813,22813,23399,23401,23402,23403" "E484K,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Approximately as infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of the individual variants)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23053,23054,23055,23060,23061,23062,23063" "E484K,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.4 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.5 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.4 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~17.5x folds more significant in 9 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Values taken 28 days after booster dose was given for BBIBP-CorVvaccine to 390 participants with 130 participants in the 0-14d-10m, 0-21d-10m and 0-28d-10m group. The geometric mean titers (GMT) of neutralizing antibody in 0-28d-10m and 0-21d-10m group were significantly higher than 0-14d-10m group at month 3, month 6 and month 10 after the second dose. A sharply decrease by 4.85-fold (GMT: 94.4-20.3), 4.67-fold (GMT: 134.4-28.8) and 4.49-fold (GMT: 145.5-32.4) was observed from day 28 to month 10 after the second dose in 0-14d-10m, 0-21d-10m and 0-28d-10m group, respectively, and they had similar decline kinetics." "" "" "" "Yao T" "2022" "https://doi.org/10.1101/2022.06.22.22276690" "doi:10.1101/2022.06.22.22276690" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Omicron neutralizing antibodies is 0.686x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~100x folds more significant in 3 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Viral load from oral swabs from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Viral load from lung tissue from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)]" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)]" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Protection against symptomatic infection caused by Beta/Gamma (assumed by combined presence of N501Y and E484K) was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%)." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Omicron neutralizing antibodies is 0.722x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 20 sera from BNT162b2 mRNA vaccine inoculated participants, 6 displayed mild (2x) reductions in neutralization. This variant combination showed the highest reduction, but the magnitude of the differences was small compared to the >4x differences in HA-inhibition titers that have been used to signal potential need for a strain change in influenza vaccines." "" "" "" "Xie" "2021" "https://doi.org/10.1038/s41591-021-01270-4" "doi:10.1038/s41591-021-01270-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In the case of VOC B.1.1.7+E484K, the addition of the E484K mutation to N501Y further increased the affinity, to ~15 fold higher than WT RBD (KD ~5 nM), by further increasing the k(on) as measured by surface plasmon resonance. Because the higher k(on) could result in mass transfer limiting binding, we confirmed that the kinetic measurement for this variant was not substantially affected by varying levels of immobilization." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.0015x fold change in IC50 in B.1.1.529 Omicron" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.025x fold change in IC50 in B.1.1.529 Omicron" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Omicron Molnupiravir (MK-4482) had no statistically significant change." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.5 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~11x, Vero ~10x, and Calu-3 ~11x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~12x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of 501 and 484)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied]" "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Pseudotyped viruses for B.1.618 was 2.5-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. [details on the convalescent patient sera collection are not abundantly clear in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, RBD-specific mutation E484Q did not significantly confer infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 1.34x drop in neutralization (NT50) [mostly from a single serum]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.618 was 2.7-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 3-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~4x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The estimated vaccine effectiveness against R.1 strain SARS-CoV-2 infection among residents in a Kentucky skilled nursing facility was 66.2% (95% CI = 40.5%–80.8%) and among health care workers was 75.9% (95% CI = 32.5%–91.4%) in the cohort of only those 14d+ post-vaccination Pfizer booster dose. VE against symptomatic COVID-19 was 86.5% (95% CI = 65.6%–94.7%) among residents and 87.1% (95% CI = 46.4%–96.9%) among HCP. VE against hospitalization was 94.4% (95% CI = 73.9%–98.8%) among residents; no HCP were hospitalized. Three residents died, two of whom were unvaccinated (VE = 94.4%; 95% CI = 44.6%–99.4%)." "" "" "" "Cavanaugh" "2021" "https://doi.org/10.15585/mmwr.mm7017e2" "doi:10.15585/mmwr.mm7017e2" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs]" "" "" "" "Sapkal" "2021" "https://doi.org/10.1101/2021.04.30.441559" "doi:10.1101/2021.04.30.441559" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs]" "" "" "" "Sapkal" "2021" "https://doi.org/10.1101/2021.04.30.441559" "doi:10.1101/2021.04.30.441559" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the P.1 & P.2 lineages of SARS-CoV-2 in Brazil. The Brazilian arm of the Phase 3 double blind study showed severe/critical disease VE of 81.9% (95% CI: 17.0-98.1), and moderate to severe/critical disease VE of 66.2% (95% CI: 51.0-77.1). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 69.3% of mostly severe infections sequenced as of this report, 69.4% were of P.2 lineage [defining lineage SNPs reported here]." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped P.2 virus has reduced neutralization activity vs wild type: 5.8x (30 sera Pfizer median 9 days post 2nd dose) and 2.9x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed in 4 separate mink farms in Denmark, but not humans, potential adaptation (diff set of farms than N501T)." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutation causes a greater than 100x fold change in IC50 of Ensovibep." "" "" "" "Rothenberger" "2021" "https://doi.org/10.1101/2021.02.03.429164v4" "doi:10.1101/2021.02.03.429164v4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutation causes a greater than 100x fold change in IC50 of Ensovibep." "" "" "" "Rothenberger" "2021" "https://doi.org/10.1101/2021.02.03.429164v4" "doi:10.1101/2021.02.03.429164v4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "IC50 relative to wildtype drops ~8x in neutralization efficiency between 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 1 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">60% drop in antibody binding (ELISA) by this variant against monoclonal antibody VH-Fc ab8." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 5 antibodies." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.13 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-07, SARS2-19, 1B07, SARS2-16 and 2B04 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed striking resistance with only 38% neutralization at the highest concentration tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Modest decrease in in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23023" "N487K" "NC_045512.2:g.1461T>G" "YP_009724390.1:p.Asn487Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, high ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Based on structural modelling, this change detected on day 128 sequencing in a chronically infected patient would alter an extensive network of polar interactions with antibody residue R94VH, a germline antibody residue that is conserved in all of the potent VH3-53/3-66-derived antibodies isolated from a convalescent donor 5 weeks after infection." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.11 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-32." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 3 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2/3 mAb C603 modestly selected for the emergence of this mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (3 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23063" "Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This Spike pseudotype for Day 146 virus from a chronically infected patient was completely resistent to REGN10933. The variant had a 4-fold decrease in REGN10987 neutralization sensitivity (2nd component of the Regeneron mAb cocktail)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23063" "Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 146 virus from a chronically infected patient: resistant to neutralization by mAb C1A-B12, and was still resistant to the affinity enhanced antibodies derived from it (i.e. no affinity maturation effect on neutralization)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23063" "Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 146 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 146 S pseudotype was resistant to neutralization." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490V" "NC_045512.2:g.1468T>G" "YP_009724390.1:p.Phe490Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) resistant to 3 individual sera at >4x" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs X593, 261-262, H4, and P2B-2F6" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 23% of supernatant sequences) after C121 monoclonal antibody assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in binding efficiency vs wild type for mAbs CB6/LY-CoV16 and LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2 mAb C627 modestly selected for the emergence of this mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Dominant (70%) in day 21 of prolonged infection in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then nearly disappearing (<5%) by day 27." "" "" "" "Chen" "2021" "https://doi.org/10.1101/2021.04.08.21254791" "doi:10.1101/2021.04.08.21254791" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 2 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, S484P shows a slightly resistant profile across both timepoints (i.e. resistant to immune cell somatic mutation evolution)" "" "" "" "Greaney" "2021" "https://doi.org/10.1016/j.chom.2021.02.003" "doi:10.1016/j.chom.2021.02.003" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-01 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Minor variant selected in late rounds of an in vitro evolution experiment for ACE2 binding. Shown to increase the thermostability but decrease the association rate constant of the RBD to ACE2" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using molecular dynamic simulation, the mildly (~1kcal/mol) enhanced binding energy of this variant is primarily contributed by Tyr505 (−4.98 kcal/mol) which is now involved in a strong hydrogen bonding network with Arg393. Another important energetic contribution comes from the altered orientation of Tyr41 which is now involved with two hydrogen-bonding interactions with Asp355 and Thr500." "" "" "" "" "2021" "https://doi.org/10.1016/j.bbrc.2021.01.035" "doi:10.1016/j.bbrc.2021.01.035" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Regdanvimab lost ~32x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23048" "G496S" "NC_045512.2:g.1486G>A" "YP_009724390.1:p.Gly496Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23053,23054,23055,23060,23061,23062,23063" "Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. The extent of affinity increase with Q498R and N501Y is not exactly quantified, as E484K always emerged with this duo during in vitro evolution." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome" "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~8x binding against this isolated mutation. Regdanvimab lost ~6x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "Variant within the six key residues in the receptor binding domain (RBD). Independently reported in UK, Australia (same origin as UK), and South Africa (independent origin)." "" "" "" "Flores-Alanis" "2021" "https://doi.org/10.3390/pathogens10020184" "doi:10.3390/pathogens10020184" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C663, and to a lesser extent C613." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Utilizing shark derived vnarbodies, S375F mutation on Omicron RBD disrupts the structure of β-strand, which inhibits binding with 20G6. 20G6 binds to a hidden epitope on RBD which is highly conserved in sarbecoviruses." "" "" "" "Feng" "2022" "https://doi.org/10.1002/smtd.202200387" "doi:10.1002/smtd.202200387" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.2x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 and day 14 post-2nd dose) against a recombinant single variant virus (modified replicating WA-1 cDNA clone) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.69 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape by lineage Alpha [defined here as N501Y positive, but E484K negative]." "" "" "" "Chung" "2021" "https://doi.org/10.1136/bmj.n1943" "doi:10.1136/bmj.n1943" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In 30 samples collected 111 to 260 days post onset of symptoms, the covalescent plasma can neutralize both the reference USA-WA1/2020 strain and the mouse adapted strain that contains the N501Y spike mutation with similar efficiency." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The N501Y mutation had the biggest effect on ACE2 affinity of any VOC mutation tested, increasing the affinity ~10 fold to KD ~7 nM, by increasing the k(on) ~1.8 fold and decreasing the k(off) by ~ 7 fold as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a modest decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Human sera from 6 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) can neutralize both the reference USA-WA1/2020 strain and the mouse adapted SARS-CoV-2 strain that contains the N501Y spike mutation with similar efficiency." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "As measured by surface plasmon resonance, RBD with the N501Y mutation alone showed a mean 2.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x)" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation alone accounts for most of the increased infectivity of the Alpha variant, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters, and Vero E6 (NHP) and Calu-3 (human) cell lines." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.03.08.434499" "doi:10.1101/2021.03.08.434499" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Lowered the neutralization potency of mAb COVA1-12 to the limit of the assay. Decrease in potency was observed against the N501Y pseudotype for the cluster IX mAb COVA2-17." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Vaccinated, but not post-infection sera, show decreased average T cell response to an N501Y peptide. When we primed transgenic mice expressing human HLA-DRB1*0401 with the Wuhan Hu-1 peptide pool, T cell responses to the B.1.1.7 variant peptide pool were significantly reduced (p = 0.0286). Furthermore, the T cell response to the spike N501Y mutation common to all three of the current VOC was ablated." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In silico methods (PyMOL and PDBePISA) involving mutagenesis (N501Y mutation) and interface analysis focusing on the Spike RDB-ACE2 interaction showed that the SARS-CoV-2 N501Y mutant (lineage B.1.1.7) establishes a more significant number of interactions relating to the mutant residue Y501 (Spike RDB) with residues Y41 and K353 (ACE2). This finding shows that the increased infectivity of SARS-CoV-2 lineage B.1.1.7 is associated with the interaction force between the Spike RBD Y501 mutant residue with the ACE2 receptor, which in this strain is increased." "" "" "" "" "2021" "https://doi.org/10.1101/2020.12.29.424708" "doi:10.1101/2020.12.29.424708" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Of 50 mAbs tested, major loss of neutralization observed for S2X128, S2D8, S2X192, S2D19, S2H14, S2H19." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x)" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Contrary to other reports on N501Y containing lineages (i.e. with additional mutations), N501Y alone may have an even greater affinity for a human monoclonal antibody specific for wild type. These results suggest that the individual N501Y mutation does not contribute to altered viral properties by itself, but may contribute to a collective conformational shift produced by multiple mutations." "" "" "" "Klegerman" "2021" "https://doi.org/10.1101/2021.04.26.441517" "doi:10.1101/2021.04.26.441517" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slightly increased infection rate amongst the cells. [in what is essentially a replicate experiment in the same paper, because each B.1.351 lineage variant was independetly evaluated and N501 is in both lineages, a significant decrease was observed, therefore the error bars described in this paper should be interpreted carefully]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The most frequent RBM mutation N501Y (165,519 instances) makes defective the atypical N-glycosylation sequon NGV 501-503, becoming a key RBM position for the interaction with hACE2-binding hotspot 353." "" "" "" "Gamez" "2021" "https://doi.org/10.1101/2021.04.09.439154" "doi:10.1101/2021.04.09.439154" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "0.7x reduction in neutralization by key variant in several variants of concern in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,22810,22811,22812,22813,22813" "N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~20x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~6x binding against this double mutation. M396 lost ~10x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,22810,22811,22812,22813,22813,23012" "N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In post-vaccination sera from individuals who received one (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) of the BNT162b2 Pfizer vaccine, an average 6.8x reduction in neutralization efficacy of this B.1.351 key variants pseudotype lentivirus vs D614G was observed." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,22810,22811,22812,22813,22813,23012" "N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "~7x reduction in neutralization by key B.1.351 lineage RBD variant combination in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Two of the cohort showed no neutralization against this variant." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23012" "N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~64x binding against this double mutation. COR-101 lost ~50x binding against this double mutation. Casirivimab lost ~250x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~32x binding against this double mutation. Tixagevimab lost ~10x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23271" "N501Y,N501Y,N501Y,N501Y,A570D" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Partial sequencing of S gene reveals two cases of probable early 2021 B.1.1.7 lineage reinfection from non-B.1.1.7 original cases in Lombardy, with 45 to 90 days between infections (less than the typical 90 day guideline for this call). Patients were 56 and 58yo, immunocompenent, with one a former smoker with obesity and dyslipidemia. One case required intubation during first infection, but presented with mild symptoms upon reinfection. The other case convalesced at home during the first episode, but required CPAP support in the subacute clinical unit upon reinfection." "" "" "" "Novazzi" "2021" "https://doi.org/10.1002/jmv.27066" "doi:10.1002/jmv.27066" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~9x, Vero ~8x, and Calu-3 ~8x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~13x, Vero ~10x, and Calu-3 ~10x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed no change in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H (""Ohio"") lineage was neutralized similarly to D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells for ACE2 affinity changes vs D614G alone, showing a ~70% drop in IC50 (i.e. increased affinity)." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23521,23522,23524,23525" "N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23071,23074,23075" "Y505H,Y505H,Y505H" "NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed first in a single tiger (cohort of 5), potential adaptation." "" "" "" "McAloose" "2020" "https://doi.org/10.1128/mBio.02220-20" "doi:10.1128/mBio.02220-20" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23071,23074,23075" "Y505H,Y505H,Y505H" "NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23102" "S514T" "NC_045512.2:g.1540T>A" "YP_009724390.1:p.Ser514Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23108" "E516Q" "NC_045512.2:g.1546G>C" "YP_009724390.1:p.Glu516Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23115" "L518Q" "NC_045512.2:g.1553T>A" "YP_009724390.1:p.Leu518Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23120" "A520S" "NC_045512.2:g.1558G>T" "YP_009724390.1:p.Ala520Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "CR3022 (SARS-targeting mAb) cross-reactivity lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23148" "K529T" "NC_045512.2:g.1586A>C" "YP_009724390.1:p.Lys529Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing statistically significant increased infection rate amongst the cells." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated that there is very little free energy change (ddG. -0.02 kcal/mol) for this variant (i.e. approx. same stability as wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant raises PIWAS epitope score from 3.6% to 6.2% (improved immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23373" "T604I" "NC_045512.2:g.1811C>T" "YP_009724390.1:p.Thr604Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a lentivirus virus pseudotyped with D614G Spike, sera from vaccinated individuals who received the second dose (9–11 days post-second dose of Pfizer) exhibited a robust neutralizing potential, with a mean NT50 value of 99,000. This was an average of a 2-fold increase, relative to sera drawn from the individuals who received one dose of vaccination—mean NT50 dilution of 51,300. Importantly, a 6-fold increase in mean NT50 dilution was obtained when sera from the first vaccination dose was compared to convalescent sera from cohort with severe disease (NT50 51,000 vs 8,700) 21 to 63 days post-onset." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 2.5 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to wild type, D614G showed increased infectivity (ie. cold stability) after storage at -20°C for up to 30 days." "" "" "" "Huang" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped D614G virus has reduced neutralization activity vs wild type: 1.2x (37 sera Pfizer median 9 days post 2nd dose, 37 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.05x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.45x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.43x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 1.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In four cell lines (including 293T-hACE2 cells), this mutation combination increases infectivity vs D614G alone" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation (a.k.a. ""Doug"") outside the receptor binding domain, while highly favorable to improved human-human transmission, decreases transduction in naked mole-rat (Heterocephalus glaber) fibroblast and Japanese pipistrelle bat (Pipistrellus abramus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Weissman" "2020" "https://doi.org/10.1101/2020.07.22.20159905" "doi:10.1101/2020.07.22.20159905" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 conferred a nearly two-fold infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD mutation conferred a 4.85x drop in neutralization (NT50)." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Negative stain EM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Weissman" "2020" "https://doi.org/10.1101/2020.07.22.20159905" "doi:10.1101/2020.07.22.20159905" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of ""one-up"" trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.35x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission." "" "" "" "Plante" "2020" "https://doi.org/10.1038/s41586-020-2895-3" "doi:10.1038/s41586-020-2895-3" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses." "" "" "" "Ozono" "2020" "https://doi.org/10.1038/s41467-021-21118-2" "doi:10.1038/s41467-021-21118-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses." "" "" "" "Ozono" "2020" "https://doi.org/10.1038/s41467-021-21118-2" "doi:10.1038/s41467-021-21118-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Studying 94 COVID-19 extended infection cases with genomics April 1 to October 17, 2020, one case developed 23 mutations in a 19 day period, including this combination in Spike." "" "" "" "Landis" "2021" "https://doi.org/10.1101/2021.05.08.21256775" "doi:10.1101/2021.05.08.21256775" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The increased transduction with Spike D614G ranged from 1.3- to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2 and from 1.5- to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction." "" "" "" "Daniloski" "2021" "https://doi.org/10.7554/eLife.65365" "doi:10.7554/eLife.65365" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.97x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a slight decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.53x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575" "D614G,D614G,D614G,D614G,L5F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.1x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575" "D614G,D614G,D614G,D614G,L5F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.23x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575" "D614G,D614G,D614G,D614G,L5F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664" "D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.526) showed a 1.02x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664" "D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.526) showed a 1.78x increase in binding (KD) relative to D614G, even though each variant independently decreases binding." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664" "D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.526) showed a 1.34x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600" "D614G,D614G,D614G,D614G,S13I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600" "D614G,D614G,D614G,D614G,S13I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.42x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600" "D614G,D614G,D614G,D614G,S13I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600,22018,22915,22916,22917" "D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. [Stark contrast to 2.15x increase in binding by convalescent plasma 8 months post infection, presumably via memory B cell affinity maturation against L452R effects] 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600,22018,22915,22916,22917" "D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.429 aka Epsilon) showed a 2.82x increase in binding (KD) relative to D614G, indicating a strong marginal effect for L452R." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600,22018,22915,22916,22917" "D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, indicating ablated marginal effect from L452R." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614" "D614G,D614G,D614G,D614G,L18F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.07x decrease in binding (KD) relative to D614G. Compare to increased binding in full Spike variant complements for major lineages containing this variant subset: 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614" "D614G,D614G,D614G,D614G,L18F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.66x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Compare to decreased binding in full Spike variant complements for major lineages containing this variant subset: 0.96x (B.1.351 aka Beta), 0.77x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614" "D614G,D614G,D614G,D614G,L18F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.30x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.28x increase (B.1.351 aka Beta), and 1.14x decrease (P.1 aka Gamma). 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.17x increase (B.1.351 aka Beta), and 1.47x decrease (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing P.1 aka Gamma) showed a 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing P.1 aka Gamma) showed a 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing P.1 aka Gamma) showed a 4.24x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664" "D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing B.1.351 aka Beta) showed a 1.04x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, in contrast to the largely positive binding values for each individual mutation that comprises the set." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664" "D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing B.1.351 aka Beta) showed a 1.28x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. It shows a 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664" "D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.351 aka Beta) showed a 3.56x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21621" "D614G,D614G,D614G,D614G,T20N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.39x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21621" "D614G,D614G,D614G,D614G,T20N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.96x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21621" "D614G,D614G,D614G,D614G,T20N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21638" "D614G,D614G,D614G,D614G,P26S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.58x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21638" "D614G,D614G,D614G,D614G,P26S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.23x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21638" "D614G,D614G,D614G,D614G,P26S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.33x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.51x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing B.1.1.7 aka Alpha) showed no change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.28x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing B.1.1.7 aka Alpha) showed a 1.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21761,21762,21763,21764,21765,21766,21766,21761,21762,21763,21764,21765,21766,21766,23060,23061,23062,23063,23271,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.1.7 aka Alpha) had 5.43x increased binding relative to D614G alone." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21801" "D614G,D614G,D614G,D614G,D80A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination showed no change relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21801" "D614G,D614G,D614G,D614G,D80A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.64x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.35x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21801" "D614G,D614G,D614G,D614G,D80A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21846" "D614G,D614G,D614G,D614G,T95I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21846" "D614G,D614G,D614G,D614G,T95I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21846" "D614G,D614G,D614G,D614G,T95I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21974" "D614G,D614G,D614G,D614G,D138Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21974" "D614G,D614G,D614G,D614G,D138Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21974" "D614G,D614G,D614G,D614G,D138Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.32x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22018" "D614G,D614G,D614G,D614G,W152C" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.15x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22018" "D614G,D614G,D614G,D614G,W152C" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22018" "D614G,D614G,D614G,D614G,W152C" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.03x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22132" "D614G,D614G,D614G,D614G,R190S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.59x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22132" "D614G,D614G,D614G,D614G,R190S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.82x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22132" "D614G,D614G,D614G,D614G,R190S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22206" "D614G,D614G,D614G,D614G,D215G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.19x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22206" "D614G,D614G,D614G,D614G,D215G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.79x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22206" "D614G,D614G,D614G,D614G,D215G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D253G,D253G,D253G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D253G,D253G,D253G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.08x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D253G,D253G,D253G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22810,22811,22812,22813,22813" "D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22810,22811,22812,22813,22813" "D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.76x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.75x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22810,22811,22812,22813,22813" "D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22812" "D614G,D614G,D614G,D614G,K417T" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.28x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22812" "D614G,D614G,D614G,D614G,K417T" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22812" "D614G,D614G,D614G,D614G,K417T" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.66x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.05x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.16x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 6.2-fold lower (95% CI: 11.8x-14.3x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 4.2x-fold lower (95% CI: 0.15x-0.20x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "paired testing of vaccine sera against ancestral virus compared to Omicron BA.1 shows that 3-dose vaccine regimen provides over 50x fold increase in protection against Omicron(B.1.1.529 [BA.1]) compared to a 2-dose regimen." "" "" "" "Hao" "2022" "https://doi.org/10.1101/2022.08.12.22278720" "doi:10.1101/2022.08.12.22278720" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 28.7x-fold lower (95% CI: 0.03x-0.05) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "4th antigenic exposure with Omicron (B.1.1.529 [BA.1])(n=29) infection increased variant specific plasma antibody and memory B cell responses as well as overall increased strain specific memory in individuals aged 22 –79 years, median age=33.5 years. Data collected 2.4 months after 3rd vaccination." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21761,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21762,21763,21764,21765,21766,21766,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 3.4-fold lower (95% CI: 3.2x-3.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 3.9x-fold lower (95% CI: 0.14x-0.17x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 78fM for binding to the Omicron BA.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 4.5-fold lower (95% CI: 4.3x-4.7x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 4.2-fold lower (95% CI: 5.8x-6.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 3.9x-fold lower (95% CI: 0.14x-0.18x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23012" "D614G,D614G,D614G,D614G,E484K" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.42x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23012" "D614G,D614G,D614G,D614G,E484K" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23012" "D614G,D614G,D614G,D614G,E484K" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This variant appears twice in the experiments, with slightly different affinities (both ~1.2x decrease in binding relative to D614G) using flow cytometry and ACE2 ectodomains-Fc portion IgG complex." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23060,23061,23062,23063" "D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23060,23061,23062,23063" "D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23060,23061,23062,23063" "D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.52x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis). Compare to full Spike variant complements for major lineages containing this variant subset: 5.43x (B.1.1.7 aka Alpha), 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23271" "D614G,D614G,D614G,D614G,A570D" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23271" "D614G,D614G,D614G,D614G,A570D" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23271" "D614G,D614G,D614G,D614G,A570D" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.18x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23521,23522,23524,23525" "D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23521,23522,23524,23525" "D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.21x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23521,23522,23524,23525" "D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.48x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant change in virus neutralzation by 18 Pfizer two dose vaccinee sera compared to B.1.1.7. [results without including the used mutation A27S likely generalizable, as this is not a lineage defining mutation]" "" "" "" "Zuckerman" "2021" "https://doi.org/10.1101/2021.03.25.21253908" "doi:10.1101/2021.03.25.21253908" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.26x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23664" "D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23664" "D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23664" "D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed essentially no change in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23709" "D614G,D614G,D614G,D614G,T716I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.12x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23709" "D614G,D614G,D614G,D614G,T716I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23709" "D614G,D614G,D614G,D614G,T716I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.58x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24506" "D614G,D614G,D614G,D614G,S982A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24506" "D614G,D614G,D614G,D614G,S982A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.3x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24506" "D614G,D614G,D614G,D614G,S982A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24642" "D614G,D614G,D614G,D614G,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.69x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24642" "D614G,D614G,D614G,D614G,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.22x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24642" "D614G,D614G,D614G,D614G,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.56x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24914" "D614G,D614G,D614G,D614G,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24914" "D614G,D614G,D614G,D614G,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x increase in binding (KD) relative to D614G, mostly due to decreased in ""off-rate"" a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24914" "D614G,D614G,D614G,D614G,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.96x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23429" "A623T" "NC_045512.2:g.1867G>A" "YP_009724390.1:p.Ala623Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain increases the virus transduction rate in tree shrew (Tupaia belangeri), (as it does in humans) according to pseudotyped VSV experiments." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.87 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Six minks were intranasally infected with WA1 isolate, all developed this mutation during infection." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23587,23587" "Q675H,Q675H" "NC_045512.2:g.2025G>C,NC_045512.2:g.2025G>T" "YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly enhanced the ability of the pseudotyped VSV to infect fat-tailed gerbil (Pachyuromys duprasi) kidney cell cultures, with a transduction rate of 13.4%, close to the 15.7% in epithelial-like human Huh-7 cells while starting from a significantly lower wildtype (Wuhan-Hu-1 Spike VSVdeltaG psuedotype) rate." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681R" "NC_045512.2:g.2042C>G" "YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. [PG: Inferred by conservative AA substitution of described P681H]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic." "" "" "" "Johnson" "2020" "https://doi.org/10.1101/2020.08.26.268854" "doi:10.1101/2020.08.26.268854" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In the absence of N501Y, this Alpha lineage change in the furin clevage site did NOT show significant increase in infectivity relative to wild type, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.03.08.434499" "doi:10.1101/2021.03.08.434499" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry)." "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry)." "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing NO statistically significant infection rate change amongst the cells, suggesting that furin cleavage typically used for cell entry is not affected by this change one amino acid upstream of the RXXR recognition pattern." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 0.9x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic." "" "" "" "Johnson" "2020" "https://doi.org/10.1101/2020.08.26.268854" "doi:10.1101/2020.08.26.268854" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681R" "NC_045512.2:g.2042C>G" "YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). [Inference from similar positively charged substitution P681H actually described in the work]" "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "While the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC)." "" "" "" "Lubinski" "2021" "https://doi.org/10.1101/2021.04.06.438731" "doi:10.1101/2021.04.06.438731" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23399,23401,23402,23403" "P681R,D614G,D614G,D614G,D614G" "NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Quantification of the band intensities showed that the P681R mutation, which lies near the proteolytic processing site, caused a small increase in proteolytic processing as measured by a 2-fold decrease in the ratio of S/S2." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23664" "A701V" "NC_045512.2:g.2102C>T" "YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23664" "A701V" "NC_045512.2:g.2102C>T" "YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.33 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant increases PIWAS epitope score from 0.69% to 2.3% Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain showed a decreased capacity to transduce PK-15 (pig kidney, Sus scrofa) and PaKi (black flying fox kidney, Pteropus alecto) cell line cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed first in a single tiger (cohort of 5), potential adaptation." "" "" "" "McAloose" "2020" "https://doi.org/10.1128/mBio.02220-20" "doi:10.1128/mBio.02220-20" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. T716I was expressed at significantly lower level, accounting for the decreased infectivity of this spike protein. This property may be specific to spike protein biosynthesis in 293T cells and is not likely to reflect the situation in vivo given the reported increase in infectivity of the B.1.1.7 virus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23897" "Q779K" "NC_045512.2:g.2335C>A" "YP_009724390.1:p.Gln779Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 20% appearance in 2 passages against Regeneron monoclonal antibody RGN10989 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23948" "D796H" "NC_045512.2:g.2386G>C" "YP_009724390.1:p.Asp796His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Fatal COVID-19 complications in immunocomprimised patient after immune escape from convalescent plasma" "" "" "" "Kemp" "2020" "https://doi.org/10.1101/2020.12.05.20241927" "doi:10.1101/2020.12.05.20241927" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24000" "S813I" "NC_045512.2:g.2438G>T" "YP_009724390.1:p.Ser813Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb B38" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24077" "D839N" "NC_045512.2:g.2515G>A" "YP_009724390.1:p.Asp839Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry." "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24077" "D839Y" "NC_045512.2:g.2515G>T" "YP_009724390.1:p.Asp839Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry." "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24130" "N856K" "NC_045512.2:g.2568C>A" "YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch." "" "" "" "Lucaci" "2021" "" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24170" "I870V" "NC_045512.2:g.2608A>G" "YP_009724390.1:p.Ile870Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Appeared at same time as T478K,S494P but listed separately due to distance and different domains affected in the Spike (i.e. putatively an independent mutation from a functional standpoint since the former are from S1, the latter from S2)." "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24377,24378" "S939F,S939F" "NC_045512.2:g.2816C>T,NC_045512.2:g.2816C>T" "YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 6/20 convalescent sera was significantly lower against this single variant pseudotyped virus model, showing similar patterns to the pseudotyped virus model of B.1.1.7." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (70%) increase in infection rate amongst the cells, hence this individual variant is likely to significantly contribute to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24642" "T1027I" "NC_045512.2:g.3080C>T" "YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 1.51 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Mutation is predicted to lose the T cell epitope for people carrying DRB1*0301 and DRB1*0401, but not for example in those who are DRB1*0701 or DRB1*1501 who would be predicted to show an enhanced response. This is also observed in a study of 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25046" "P1162S" "NC_045512.2:g.3484C>T" "YP_009724390.1:p.Pro1162Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25249,25249,25249" "M1229I,M1229I,M1229I" "NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25350" "P1263L" "NC_045512.2:g.3788C>T" "YP_009724390.1:p.Pro1263Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant in the cytoplasmic tail, shown in vitro to increase Spike subunit fusion required for cell entry" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25855" "D155Y" "NC_045512.2:g.463G>T" "YP_009724391.1:p.Asp155Tyr" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "caveolin binding" "" "" "In silico, this mutation is the only one weakening ORF3a's binding affinity for caveolin-1 (essential for entry and endomembrane trafficking of SARS-CoV-2). This mutation is a widespread homoplasy in 20A and 20B lineages." "" "" "" "Gupta" "2021" "https://doi.org/10.1101/2021.03.26.437194" "doi:10.1101/2021.03.26.437194" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26029" "Q213K" "NC_045512.2:g.637C>A" "YP_009724391.1:p.Gln213Lys" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*01:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26029" "Q213K" "NC_045512.2:g.637C>A" "YP_009724391.1:p.Gln213Lys" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*01:01-restricted CD8+ ORF3a epitope, which is otherwise ""consistently dominant and of high magnitude""." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26256" "F4F" "NC_045512.2:g.12C>T" "YP_009724392.1:p.Phe4Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26268,26269,26270" "T9I,T9I,T9I" "NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T" "YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~300 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26268,26269,26270" "T9I,T9I,T9I" "NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T" "YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26296" "L18I" "NC_045512.2:g.52C>A" "YP_009724392.1:p.Leu18Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (47x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26299" "L19F" "NC_045512.2:g.55C>T" "YP_009724392.1:p.Leu19Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26312" "F23C" "NC_045512.2:g.68T>G" "YP_009724392.1:p.Phe23Cys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~8.8 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26314" "V24M" "NC_045512.2:g.70G>A" "YP_009724392.1:p.Val24Met" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26319" "V25V" "NC_045512.2:g.75A>G" "YP_009724392.1:p.Val25Val" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (45x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26333" "T30I" "NC_045512.2:g.89C>T" "YP_009724392.1:p.Thr30Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26353" "L37F" "NC_045512.2:g.109C>T" "YP_009724392.1:p.Leu37Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26395" "L51I" "NC_045512.2:g.151C>A" "YP_009724392.1:p.Leu51Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (47x overrepresentation vs expected count of ~24 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26416" "V58L" "NC_045512.2:g.172G>C" "YP_009724392.1:p.Val58Leu" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26428" "V62F" "NC_045512.2:g.184G>T" "YP_009724392.1:p.Val62Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (18x overrepresentation vs expected count of ~333 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26442" "N66K" "NC_045512.2:g.198T>G" "YP_009724392.1:p.Asn66Lys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~23 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26447" "S68F" "NC_045512.2:g.203C>T" "YP_009724392.1:p.Ser68Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26447" "S68C" "NC_045512.2:g.203C>G" "YP_009724392.1:p.Ser68Cys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (58x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26456" "P71R" "NC_045512.2:g.212C>G" "YP_009724392.1:p.Pro71Arg" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26467" "V75L" "NC_045512.2:g.223G>C" "YP_009724392.1:p.Val75Leu" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (3762.7x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526" "A2S" "NC_045512.2:g.4G>T" "YP_009724393.1:p.Ala2Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Emergent as 16% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing." "" "" "" "Avanzato" "2020" "https://doi.org/10.1016/j.cell.2020.10.049" "doi:10.1016/j.cell.2020.10.049" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526" "A2S" "NC_045512.2:g.4G>T" "YP_009724393.1:p.Ala2Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (38x overrepresentation vs expected count of ~334 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526,26527,26529" "D3H,D3H,D3H" "NC_045512.2:g.7G>C,NC_045512.2:g.7G>C,NC_045512.2:g.7G>C" "YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (227x overrepresentation vs expected count of ~14 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26528,26528,26528" "A2A,A2A,A2A" "NC_045512.2:g.6A>T,NC_045512.2:g.6A>G,NC_045512.2:g.6A>C" "YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (25x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26530" "D3G" "NC_045512.2:g.8A>G" "YP_009724393.1:p.Asp3Gly" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (31x overrepresentation vs expected count of ~53 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26542" "T7I" "NC_045512.2:g.20C>T" "YP_009724393.1:p.Thr7Ile" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26546" "I8I" "NC_045512.2:g.24T>C" "YP_009724393.1:p.Ile8Ile" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~80 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26573,26576,26577" "Q19E,Q19E,Q19E" "NC_045512.2:g.55C>G,NC_045512.2:g.55C>G,NC_045512.2:g.55C>G" "YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~8 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26620" "C33S" "NC_045512.2:g.98G>C" "YP_009724393.1:p.Cys33Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~32 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26645" "N41N" "NC_045512.2:g.123C>T" "YP_009724393.1:p.Asn41Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (19x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26681" "F53F" "NC_045512.2:g.159C>T" "YP_009724393.1:p.Phe53Phe" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (163x overrepresentation vs expected count of ~567 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26730" "V70L" "NC_045512.2:g.208G>C" "YP_009724393.1:p.Val70Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26748" "I76V" "NC_045512.2:g.226A>G" "YP_009724393.1:p.Ile76Val" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26748" "I76L" "NC_045512.2:g.226A>C" "YP_009724393.1:p.Ile76Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~9 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26749" "I76T" "NC_045512.2:g.227T>C" "YP_009724393.1:p.Ile76Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (19x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26767" "I82T" "NC_045512.2:g.245T>C" "YP_009724393.1:p.Ile82Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "homoplasy" "" "" "This mutation presents mainly within the B.1 (44.0%) and B.1.525 (38.1%) lineages. Currently, 99.7% of the B.1.525 lineage isolates carry the M:I82T mutation. While this mutation is scattered across multiple phylogenetic clades, most cases cluster in two recent clades, suggesting a likely selective advantage in certain haplotype backgrounds." "" "" "" "Shen" "2021" "https://doi.org/10.1080/22221751.2021.1922097" "doi:10.1080/22221751.2021.1922097" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26767" "I82T" "NC_045512.2:g.245T>C" "YP_009724393.1:p.Ile82Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (67x overrepresentation vs expected count of ~42 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26801,26801,26801" "L93L,L93L,L93L" "NC_045512.2:g.279C>G,NC_045512.2:g.279C>A,NC_045512.2:g.279C>T" "YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~628 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26855,26858" "F112F,F112F" "NC_045512.2:g.336C>T,NC_045512.2:g.336C>T" "YP_009724393.1:p.Phe112Phe,YP_009724393.1:p.Phe112Phe" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~463 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26861" "N113N" "NC_045512.2:g.339T>C" "YP_009724393.1:p.Asn113Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (57x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26873" "N117N" "NC_045512.2:g.351C>T" "YP_009724393.1:p.Asn117Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26882,26882" "L120L,L120L" "NC_045512.2:g.360C>A,NC_045512.2:g.360C>T" "YP_009724393.1:p.Leu120Leu,YP_009724393.1:p.Leu120Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26894,26894" "L124L,L124L" "NC_045512.2:g.372C>T,NC_045512.2:g.372C>G" "YP_009724393.1:p.Leu124Leu,YP_009724393.1:p.Leu124Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26895" "H125Y" "NC_045512.2:g.373C>T" "YP_009724393.1:p.His125Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (22x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26895" "H125Y" "NC_045512.2:g.373C>T" "YP_009724393.1:p.His125Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARA_CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26907,26909,26909" "L129L,L129L,L129L" "NC_045512.2:g.385C>T,NC_045512.2:g.387G>A,NC_045512.2:g.387G>T" "YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26927" "E135E" "NC_045512.2:g.405A>G" "YP_009724393.1:p.Glu135Glu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (232x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26951,26951,26951" "V143V,V143V,V143V" "NC_045512.2:g.429G>C,NC_045512.2:g.429G>A,NC_045512.2:g.429G>T" "YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~508 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26966" "H148H" "NC_045512.2:g.444T>C" "YP_009724393.1:p.His148His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26972" "R150R" "NC_045512.2:g.450T>C" "YP_009724393.1:p.Arg150Arg" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~89 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26985" "H155N" "NC_045512.2:g.463C>A" "YP_009724393.1:p.His155Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26987" "H155H" "NC_045512.2:g.465T>C" "YP_009724393.1:p.His155His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27021" "E167Q" "NC_045512.2:g.499G>C" "YP_009724393.1:p.Glu167Gln" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27035,27038" "T172T,T172T" "NC_045512.2:g.516A>G,NC_045512.2:g.516A>G" "YP_009724393.1:p.Thr172Thr,YP_009724393.1:p.Thr172Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27059" "Y179Y" "NC_045512.2:g.537C>T" "YP_009724393.1:p.Tyr179Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27112" "S197T" "NC_045512.2:g.590G>C" "YP_009724393.1:p.Ser197Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (18x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27134" "Y204Y" "NC_045512.2:g.612T>C" "YP_009724393.1:p.Tyr204Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27143" "N207N" "NC_045512.2:g.621C>T" "YP_009724393.1:p.Asn207Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27147" "D209H" "NC_045512.2:g.625G>C" "YP_009724393.1:p.Asp209His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (81x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27367" "Q56X" "NC_045512.2:g.166C>T" "YP_009724394.1:p.Gln56Xaa" "" "open reading frame 6 gene (SARS-CoV-2)" "orf6 gene (SARS-CoV-2)" "open reading frame 6 protein (SARS-CoV-2)" "Orf6 protein (SARS-CoV-2)" "IFN activity" "" "" "The residues listed are determinants of the potent IFN-antagonistic activity of SARS-CoV-2 ORF6 (via blocking mRNA nuclear export)" "" "" "" "Kimura" "2020" "https://doi.org/10.2139/ssrn.3690468" "doi:10.2139/ssrn.3690468" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28144" "L84S" "NC_045512.2:g.251T>C" "YP_009724396.1:p.Leu84Ser" "" "open reading frame 8 gene (SARS-CoV-2)" "orf8 gene (SARS-CoV-2)" "open reading frame 8 protein (SARS-CoV-2)" "Orf8 protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28307,28309,28310,28311" "P13L,P13L,P13L,P13L" "NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T" "YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28307,28309,28310,28311" "P13L,P13L,P13L,P13L" "NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T" "YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13)." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28310" "P13S" "NC_045512.2:g.37C>T" "YP_009724397.2:p.Pro13Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13)." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28310" "P13S" "NC_045512.2:g.37C>T" "YP_009724397.2:p.Pro13Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*27:05." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28769" "T166A" "NC_045512.2:g.496A>G" "YP_009724397.2:p.Thr166Ala" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "Confers a significant PIWAS value decrease (reduced antigenicity)" "" "" "" "Haynes" "2020" "https://doi.org/10.1101/2020.11.23.20235002" "doi:10.1101/2020.11.23.20235002" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28853" "S194T" "NC_045512.2:g.580T>A" "YP_009724397.2:p.Ser194Thr" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28854" "S194L" "NC_045512.2:g.581C>T" "YP_009724397.2:p.Ser194Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "Mutation with a population frequency of 30% in a Mexican dataset, primarily of lineage 20B, but also present in a substantial number of 20A lineage sequences, suggesting convergent evolution." "" "" "" "Barona-Gomez" "2021" "https://doi.org/10.1101/2021.05.18.21256128" "doi:10.1101/2021.05.18.21256128" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28854" "S194L" "NC_045512.2:g.581C>T" "YP_009724397.2:p.Ser194Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In March 2021 this variant had an allele frequency of 47.62 and 7.25% in deceased patients, compared to 35.16 and 3.20% of the same variant in recovered patients, from the Gujarat and global datasets." "" "" "" "Joshi" "2021" "https://doi.org/10.3389/fgene.2021.586569" "doi:10.3389/fgene.2021.586569" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28869" "P199L" "NC_045512.2:g.596C>T" "YP_009724397.2:p.Pro199Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28879" "S202R" "NC_045512.2:g.606T>G" "YP_009724397.2:p.Ser202Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows major increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881" "R203M" "NC_045512.2:g.608G>T" "YP_009724397.2:p.Arg203Met" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows most increase in RNA content of any N mutation tested, suggesting that this mutation improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28977" "S235F" "NC_045512.2:g.704C>T" "YP_009724397.2:p.Ser235Phe" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "Substantially increases epitope and antigen scores in 2 of 579 individuals (should increase immune response). In the B1.1.7 lineage this is largely counteracted by the D3L mutation, which decreases PIWAS signal significantly in 1.5% of COVID patients, for a net neutral effect at the population level." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29239,29239" "M322I,M322I" "NC_045512.2:g.966G>A,NC_045512.2:g.966G>T" "YP_009724397.2:p.Met322Ile,YP_009724397.2:p.Met322Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "Agerer" "2021" "https://doi.org/10.1126/sciimmunol.abg6461" "doi:10.1126/sciimmunol.abg6461" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29247" "T325I" "NC_045512.2:g.974C>T" "YP_009724397.2:p.Thr325Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes partial loss of T cell line responsiveness and CTL killing ability by B*40:01-restricted CD8+ N epitope MEVTPSGTWL 322-331." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29247" "T325I" "NC_045512.2:g.974C>T" "YP_009724397.2:p.Thr325Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29266,29266" "L331F,L331F" "NC_045512.2:g.993G>T,NC_045512.2:g.993G>C" "YP_009724397.2:p.Leu331Phe,YP_009724397.2:p.Leu331Phe" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "Agerer" "2021" "https://doi.org/10.1126/sciimmunol.abg6461" "doi:10.1126/sciimmunol.abg6461" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is ""consistently dominant and of high magnitude""." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29409" "T379I" "NC_045512.2:g.1136C>T" "YP_009724397.2:p.Thr379Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "335" "R24C" "NC_045512.2:g.70C>T" "YP_009724389.1:p.Arg24Cys" "YP_009724389.1:Arg24Cys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (25x overrepresentation vs expected count of 514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "347" "V28I" "NC_045512.2:g.82G>A" "YP_009724389.1:p.Val28Ile" "YP_009724389.1:Val28Ile" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (30x overrepresentation vs expected count of 143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "383" "S40P" "NC_045512.2:g.118T>C" "YP_009724389.1:p.Ser40Pro" "YP_009724389.1:Ser40Pro" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~58 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "396" "Q44L" "NC_045512.2:g.131A>T" "YP_009724389.1:p.Gln44Leu" "YP_009724389.1:Gln44Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~19 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "443" "V60I" "NC_045512.2:g.178G>A" "YP_009724389.1:p.Val60Ile" "YP_009724389.1:Val60Ile" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "489" "D75G" "NC_045512.2:g.224A>G" "YP_009724389.1:p.Asp75Gly" "YP_009724389.1:Asp75Gly" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "490,490" "D75E,D75E" "NC_045512.2:g.225T>G,NC_045512.2:g.225T>A" "YP_009724389.1:p.Asp75Glu,YP_009724389.1:p.Asp75Glu" "YP_009724389.1:Asp75Glu,YP_009724389.1:Asp75Glu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~20 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Emergent as 22% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing." "" "" "" "Avanzato" "2020" "https://doi.org/10.1016/j.cell.2020.10.049" "doi:10.1016/j.cell.2020.10.049" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-517) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-523) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 500-523) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,509,518" "M85V,M85V,M85V" "NC_045512.2:g.253A>G,NC_045512.2:g.253A>G,NC_045512.2:g.253A>G" "YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val" "YP_009724389.1:Met85Val,YP_009724389.1:Met85Val,YP_009724389.1:Met85Val" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "508" "H81Q" "NC_045512.2:g.243T>A" "YP_009724389.1:p.His81Gln" "YP_009724389.1:His81Gln" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (30x overrepresentation vs expected count of ~20 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "510" "M85K" "NC_045512.2:g.254T>A" "YP_009724389.1:p.Met85Lys" "YP_009724389.1:Met85Lys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~12 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "561" "R99H" "NC_045512.2:g.296G>A" "YP_009724389.1:p.Arg99His" "YP_009724389.1:Arg99His" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "563" "S100C" "NC_045512.2:g.298A>T" "YP_009724389.1:p.Ser100Cys" "YP_009724389.1:Ser100Cys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (33x overrepresentation vs expected count of ~19 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "593" "H110Y" "NC_045512.2:g.328C>T" "YP_009724389.1:p.His110Tyr" "YP_009724389.1:His110Tyr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (22x overrepresentation vs expected count of ~514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "593" "H110D" "NC_045512.2:g.328C>G" "YP_009724389.1:p.His110Asp" "YP_009724389.1:His110Asp" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~11 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "606" "I114T" "NC_045512.2:g.341T>C" "YP_009724389.1:p.Ile114Thr" "YP_009724389.1:Ile114Thr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (155x overrepresentation vs expected count of ~58 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "657" "A131V" "NC_045512.2:g.392C>T" "YP_009724389.1:p.Ala131Val" "YP_009724389.1:Ala131Val" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "677" "A138T" "NC_045512.2:g.412G>A" "YP_009724389.1:p.Ala138Thr" "YP_009724389.1:Ala138Thr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "761" "S166G" "NC_045512.2:g.496A>G" "YP_009724389.1:p.Ser166Gly" "YP_009724389.1:Ser166Gly" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (132x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "798" "N178S" "NC_045512.2:g.533A>G" "YP_009724389.1:p.Asn178Ser" "YP_009724389.1:Asn178Ser" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" From df038ca6eaaa7ac90f82657eb75c19fa2c3333b3 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 12 Nov 2024 19:03:16 -0800 Subject: [PATCH 094/161] ensure PMIDs are integers --- bin/addpmids2functionalannotation.py | 4 ++-- 1 file changed, 2 insertions(+), 2 deletions(-) diff --git a/bin/addpmids2functionalannotation.py b/bin/addpmids2functionalannotation.py index c1f11271..925910db 100755 --- a/bin/addpmids2functionalannotation.py +++ b/bin/addpmids2functionalannotation.py @@ -49,9 +49,9 @@ def parse_args(): # rearrange columns functional_annotation_df = functional_annotation_df[functional_annotation_columns] - # make sure years are integers - #functional_annotation_df['publication year'] = functional_annotation_df['publication year'].astype(str).replace('.0', 'CAT', regex=False) + # make sure years and PMIDs are integers functional_annotation_df["publication year"] = functional_annotation_df["publication year"].astype('Int64') + functional_annotation_df['PMID'] = functional_annotation_df['PMID'].str.replace('.0', '', regex=False) # save to TSV functional_annotation_df.to_csv(args.outputfile, sep='\t', header=True, index=False) \ No newline at end of file From 1931c79b503131fd498733db91b6cf566115d6eb Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 12 Nov 2024 19:05:17 -0800 Subject: [PATCH 095/161] add PMIDs to functional annotation file --- ...kay_functionalAnnotation_SARSCoV2_v4.1.tsv | 1388 +++++++++++++++++ 1 file changed, 1388 insertions(+) create mode 100644 assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.1.tsv diff --git a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.1.tsv b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.1.tsv new file mode 100644 index 00000000..8bf124e6 --- /dev/null +++ b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.1.tsv @@ -0,0 +1,1388 @@ +organism reference accession reference database name nucleotide position original mutation description nucleotide mutation amino acid mutation amino acid mutation alias gene name gene symbol protein name protein symbol measured variant functional effect inferred variant functional effect viral life cycle functional effect variant functional effect description CVX code DrugBank Accession Number Antibody Registry ID author publication year URL DOI PMID peer review status curator mutation functional annotation resource +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has a 0.66x fold change in EC50 value with Remdesivir. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) viral load This mutant causes a 0.41x fold change in the infectious virus production rate. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has a 0.27x fold change in EC50 value with Remdesivir. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has an inhibition rate of virus production by Remdesivir of 0.80. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has an inhibition rate of virus production by Remdesivir of 0.78. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2:g.1438T>C YP_009724389.1:p.Phe480Leu YP_009724389.1:Phe300Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) viral load This mutant causes a 0.48x fold change in the infectious virus production rate. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.526 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for 6 convalescent sera. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 pmid:33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 pmid:33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed 3.8x reduction in IC50 serum dilution concentration for 6 convalescent sera. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 pmid:33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 pmid:34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 pmid:33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,22992,23012,23664 L5F,S477N,E484K,A701V NC_045512.2:g.13C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 114 test-positive were Iota. Two dose vaccine efficacy against Iota was 95.7 (81.7-99.0%), one dose VE was 88.8 (0.7-98.7)%. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,25186 L5F,Q1208H NC_045512.2:g.13C>T,NC_045512.2:g.3624G>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Gln1208His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Four of the convalescent sera tested showed 4-fold or greater improvement in neutralization efficiency. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21587 P9S NC_045512.2:g.25C>T YP_009724390.1:p.Pro9Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2M28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21597 S12F NC_045512.2:g.35C>T YP_009724390.1:p.Ser12Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects A variant in low % circulation, predicted to have a similar effect to the experimentally verified S12P, which introduces a new signal peptide, altering cleavage to occur between residues C15 and V16, thereby eliminating the C15-C136 disulfide bond – similarly to escape mutants at positions C15 and C136. This in turn decreases to varying degrees N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600 S13I NC_045512.2:g.38G>T YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The S13I mutation dampened binding of 5 mAbs and abrogated binding of 5 additional mAbs out of 11 neutralizing mAbs evaluated. Predicted to shift the signal peptide cleavage site from S13-Q14 to C15-V16, which can affect NTD conformation. PG: in saying S12F does not shift the signal peptide nor affect mAb binding, this manuscript appears to contradict the text of McCallum et al.'s earlier 2021 manuscript stating that S12F *does* affected some mAb binding via putative signal peptide shift. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018 S13I,W152C NC_045512.2:g.38G>T,NC_045512.2:g.456G>T YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The B.1.427/B.1.429 S13I/W152C NTD did not bind to any NTD-directed neutralizing mAbs, which are known to target a single antigenic site (antigenic site i), whereas binding of the non-neutralizing S2L20 mAb to the NTD antigenic site iv was not affected by any mutants, confirming proper retention of folding. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Lineages bearing these spike mutations comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the 'California' or 'West Coast' variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI:1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Peng 2021 https://doi.org/10.1093/cid/ciab283 doi:10.1093/cid/ciab283 pmid:33788923 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 pmid:33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 9 plasma collected 15 to 28 days after early 2020 infections, neutralization reduced 4.9-fold for B.1.427/B.1.429 compared to wildtype (D614G). In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.427/B.1.429 pseudotyped virus, as well as WT and other VOCs. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Swab samples N/NP viral RNA is approximately 2-fold higher in B.1.427/B.1.429 than in non-variant viruses. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 pmid:33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 14 of 34 RBD-specific mAbs showed reduced neutralization to the B.1.427/B.1.429 variant pseudotype. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Antibody neutralization assays showed 6.7-fold resistance against 7/8 convalescent plasma. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 pmid:33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.249 (1.7-fold). Neutralization against 10 convalescent plasma was somewhat poorer (3.1-fold). Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917 S13I,W152C,L452R,L452R,L452R NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using HIV pseudotype: Neutralization potency of 11 Moderna mRNA1273-elicited plasma (7-27 days post-2nd dose) was reduced ~2.8-fold compared to wildtype (D614G) S. It was reduced ~4-fold in 14 Pfizer/BioNtech BNT162b2-elicited plasma (7-27 days post-2nd dose). Using VSV pseudotype: we observed a 3-fold average reduction of Pfizer/BioNtech BNT162b2-elicited plasma neutralizing activity. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 pmid:34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 6 of 11 (55%) vaccine recipients (Moderna or Pfizer), showed 2x reduction in neutralization to a B.1.429 lineage virus. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 pmid:33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.427/429 reduced 2.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 2.7x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 2.3x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22916,22917,23399,23401,23402,23403,25135 S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G,K1191N NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3573G>T YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys1191Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for CAL.20C (B.1.429), and a slight decrease in CD8+ percentage (p=0.0201) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 pmid:33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21604,21604 Q14H,Q14H NC_045512.2:g.42G>C,NC_045512.2:g.42G>T YP_009724390.1:p.Gln14His,YP_009724390.1:p.Gln14His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21605 C15R NC_045512.2:g.43T>C YP_009724390.1:p.Cys15Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21606 C15F NC_045512.2:g.44G>T YP_009724390.1:p.Cys15Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 pmid:34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite 'i', but no effect on other mAbs within that supersite McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates neutralization by N-terminal-domain-targeting mAbs 4-19. Impairs neutralization by N-terminal-domain-targeting mAbs 4A8 and 2-17. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2:g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggetsing that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132 L18F,T20N,P26S,D138Y,R190S NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The neutralization titer of NTD-binding mAb159 was 133-fold reduced on P.1 compared to Victoria (~wild type), with only 64% neutralization at 10 μg/mL. Residues 20, 18, and 138 form a cluster underlying the 245–259 loop, which inserts into a groove between the light and heavy chains of Fab 159. In addition, the N-terminal residues preceding residue 18 interact with the antibody and may be perturbed. Given that there is likely a single supersite ('i') for potent NTD-binding antibodies, the binding of many of these are likely affected. Using 20 potent (primaruly anti-RBD) antibodies, neutralization was measured by a focus reduction neutralization test (FRNT) and compared with neutralization of Victoria (~wild type) and variants B.1.1.7 and B.1.351. Compared to Victoria neutralization by the mAbs was significantly impacted by P.1, with 12/20 showing > 10-fold reduction in FRNT50 titer and a number showing complete knockout of activity. The results with P.1 showed a greater impact compared to B.1.1.7 but were, as expected, similar to those with B.1.351. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 pmid:33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 12 Moderna vaccinee sera 15 days post second dose (43 days since first vaccination), an average 2.8x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 4.8x decrease against the full P.1 type vs WA-1 was observed, though overall with a higher ID50 reciprocal value. In 10 Pfizer vaccinee sera 7 days or more post second dose (28 days or more since first vaccination), an average 2.2x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.8x decrease against the full P.1 type vs WA-1 was observed, with similar variant ID50 reciprocal value. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 pmid:33688656 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure CryoEM reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the “up” position. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 pmid:33688656 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Amongst RBD-targeting Emergency Use Authorized monoclonal antibody treatments CB6, LY-CoV555 and REGN10933 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1, but REGN10987 activity remains strong. RBD-targeting monoclonal antibodies 2-15 and C121 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. N terminal domain targeting monoclonal antibodies 5-7, 4-8, 4-18 and 2-17 have abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 pmid:33688656 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In convalescent sera one month or more post-infection in Spring 2020, an average 6.5x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.4x decrease against the full P.1 type vs WA-1 was observed, with better full P.1 ID50 reciprocal value compared to the 10-mutation model. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 pmid:33688656 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Three healthcare workers (29-50yo) had confirmed P.1 [Gamma] re-infection in the Amazonas region of Brazil 3-9 months after initial infection from viruses with distinct lineage from P.1, but mild symptoms upon re-infection and evidence for infectiousness during re-infection. Naveca 2021 https://doi.org/10.21203/rs.3.rs-318392/v1 doi:10.21203/rs.3.rs-318392/v1 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection After a 128 day interval, a patient in Sao Paulo State, Brazil reinfected with P.1 (first episode likely predates P.1 emergence). Both cases were fairly mild (difficulty breathing, tiredness, dizziness and fatigue). Malta Romano 2021 https://doi.org/10.1590/S1678-9946202163036 doi:10.1590/S1678-9946202163036 pmid:33909850 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 3.0x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 349 test-positive were Gamma. Two dose vaccine efficacy against Gamma was 95.5 (90.9-97.8%), one dose VE was 74.2 (43.8-88.1%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Gamma (P.1) variant is 0.6x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 4.1x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~6x cleavage of S2 relative to WA1 (D614G) wildtype by Gamma variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but H655Y is upstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.7 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0039 for mild resistance. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Unlike wild type or B.1.1.7, P.1 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. Montagutelli 2021 https://doi.org/10.1101/2021.03.18.436013 doi:10.1101/2021.03.18.436013 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.248 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07. B.1.1.248 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.248 variant constellation in 10 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples, P=0.0020. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 pmid:33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was slightly lower against B.1.1.248 variant constellation in sera tested from most of the 15 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 16.6% in this B.1.1.248 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 pmid:33972942 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped P.1 virus has reduced neutralization activity vs wild type: 6.7x (30 sera Pfizer median 9 days post 2nd dose) and 4.5x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Among 46,884 HCWs in Manaus, Brazil vaccinated with at least one dose of CoronaVac, a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%; 95% CI, 11.3 - 71.4) in the odds of symptomatic SARS-CoV-2 infection was observed during the period 14 days or more after receiving the first dose. Estimated vaccine effectiveness of at least one dose against any SARS-CoV-2 infection was 35.1% (95% CI, −6.6 - 60.5) in the same time period. Hitchlings 2021 https://doi.org/10.1101/2021.04.07.21255081 doi:10.1101/2021.04.07.21255081 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed. Andrade 2021 https://doi.org/10.1101/2021.04.14.439719 doi:10.1101/2021.04.14.439719 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for P.1 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the P.1 variants used, using the most popular as a stand in] McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding VSV pseudotype P.1 showed 4.8-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections). Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking VSV pseudotype P.1 showed slight decrease in cell entry relative to wild type in 262T and 263T-ACE2 (kidney) cell lines. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 pmid:33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Neutralizing antibodies that were generated following a mild infection with SARS-CoV-2 B.1.128 were effective in vitro, and likely protective, against the SARS-CoV-2 P.1. variant in the majority of individuals based on 60 convalescent sera tested. Mendes-Correa 2021 https://doi.org/10.1101/2021.05.11.21256908 doi:10.1101/2021.05.11.21256908 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.15x *increase* in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness VSV pseudotype P.1 entry mediated by the S proteins of the P.1 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Cell fusion proficiency was slight impaired. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 pmid:33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 pmid:33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness P.1 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with Lilly mAb combination LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of P.1. There was also escape from neutralization of P.1 by REGN10933 (one of 2 in Regeneron's mAb cocktail) and a modest reduction in neutralization of P.1 by AstraZeneca's AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized P.1 with all reaching a plateau at 100% neutralization; interestingly, ADG30 showed a slight increase of neutralization of P.1. S309 Vir was largely unaffected, although for several viruses, including P.1, the antibody failed to completely neutralize, conceivably reflecting incomplete glycosylation at N343, since the sugar interaction is key to binding of this antibody. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 pmid:33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion PBMCs of 11 mild COVID-19 patients collected 38-80 days after symptom onset were stimulated with the 15-mer peptide pools (w/ 10 residue overlaps) from the wholle viral proteome, showing no significant CD4+ cell count effect for P.1, and a slight increase in CD8+ percentage (p=0.0195) by Activation Induced Marker (AIM) assay (cellular immunity measurement). [in the text, this increase is not noted as signficant, even though p=0.05 is used elsewhere in the text as a signficance threshold] Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 pmid:33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against P.1 at various time points using pseudovirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 85%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 pmid:34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 256 for B.1.1.7 virus. Compare to somewhat stronger neutralization titer for wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 pmid:33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525 L18F,T20N,P26S,D138Y,R190S,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The relative transmissibility of P.1 estimated at the national level (Italy) varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. PG: variant list has been abbreviated due to mixed K417 bases in this lineage, potential miscalls of deletions Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21762,21763,21764,21765,21766,21766,21761,21801,22206,22334,22600,22600,22810,22811,22812,22813,22813,22879,22881,22882,22882,22986,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,H69del,H69del,H69del,H69del,H69del,H69del,V70del,D80A,D215G,W258R,R346S,R346S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,A475V,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.772T>C,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1424C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ala475Val,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments and mutations from variants of concern completely ablates neutralization in 19 of 21 convalescents plasma collected mean 1.3 months post infection. [actual Y145del from manuscript substituted with more common Y144del description] Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801 L18F,D80A NC_045512.2:g.52C>T,NC_045512.2:g.239A>C YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The L18F and D80A of the B.1.351 lineage lead to reconfiguration of the N-terminal segment despite the disulfide between Cys16 and Cys136 that partly anchors the N-terminal peptide. The most consequential changes are probably from the triple residue deletion... which causes a shift of the nearby loop 144-155 and must also reconfigure the adjacent disorder loop (residues 246-260), both of which form part of the neutralizing epitopes...bringing large changes in the antigenic surface in this region. Cai 2021 https://doi.org/10.1101/2021.04.13.439709 doi:10.1101/2021.04.13.439709 pmid:33880477 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The 501Y.V2 to first wave IC50 ratio ranged from 6 to 200-fold. Averaging across all 7 participant convalescent sera highlighted the dramatic decrease in sensitivity to neutralization of authentic 501Y.V2 variants. PG: I'm purposefully ignoring D614G and A701V as contributors Cele 2021 https://doi.org/10.1038/s41586-021-03471-w doi:10.1038/s41586-021-03471-w pmid:33780970 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike). Riddell 2021 https://doi.org/10.1101/2021.04.17.440246 doi:10.1101/2021.04.17.440246 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pzifer vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1), but were all infected before 14 days post second vaccination. Kustin 2021 https://doi.org/10.1101/2021.04.06.21254882 doi:10.1101/2021.04.06.21254882 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In human sera 8 weeks post-vaccination with INO-4800, a ~7-fold reduction in B.1.351 neutralization was observed. Andrade 2021 https://doi.org/10.1101/2021.04.14.439719 doi:10.1101/2021.04.14.439719 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Wu 2021 https://doi.org/10.1101/2021.04.13.439482 doi:10.1101/2021.04.13.439482 pmid:33880468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness B.1.351 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of B.1.351. There was also escape from neutralization of B.1.351 by REGN10933 and a modest reduction in neutralization of B.1.351 by AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized B.1.351. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 pmid:33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.07x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy [Contrary to how this paper has been cited, Voysey et al. do NOT show evidence of decreased effectiveness of ChAdOx1 (AstraZeneca) against the South African B.1.351 lineage. Insufficient numbers reaching the primary study endpoint were available in that arm of the vaccine study to report any statistics from the South African participants. Additionally, the study period of the paper ended in November 2020, while the earliest reported case of this lineage is October (covariants.org), only becoming dominant by mid-November.] Voysey 2021 https://doi.org/10.1016/S0140-6736(20 doi:10.1016/S0140-6736(20 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR16m molecule had a 0.036x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR22 molecule had a 1.57x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.054x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.351 sample. Contrast this with 1.4-fold reduction for just the pseudovirus combination of 'key' B.1.351 mutations K417N+E484K+N501Y. WA1 and B.1.351 FRNT50 titers correlated weakly at the individual level, with some individual’s serum potently neutralizing WA1 while having FRNT50 for B.1.351 below the assay limit of detection (1:20). Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 pmid:33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.351 v2 virus has reduced neutralization activity vs wild type: 41.2x (30 sera Pfizer median 9 days post 2nd dose) and 20.8x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed for B.1.351 a CD4+ cell count decrease (29%, p=0.00063) as well as CD8+ (33%, p=0.0016) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 pmid:33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021 https://doi.org/10.1056/NEJMoa2103055 doi:10.1056/NEJMoa2103055 pmid:33951374 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Beta neutralizing antibodies is 0.899x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: while B.1.1.7 and D614G showed neutralization by nasal swab from only one different previously infected vacinee neutralizing at weeks 3 and 6, B.1.351 showed zero neutralization at either time point in any sample (and relatively impaired serum neutralization). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Beta neutralizing antibodies is 0.803x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera). Madhi 2021 https://doi.org/10.1056/NEJMoa2102214 doi:10.1056/NEJMoa2102214 pmid:33725432 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Beta Variant B.1.351 RBD significantly better than w.t. SARS-CoV-2 RBD. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals (5/9) and recipients of a only a single dose of mRNA vaccine (10/11) – heterotypic neutralization dropped to negligible levels, particularly against B.1.351. Skelly 2021 https://doi.org/10.21203/rs.3.rs-226857/v1 doi:10.21203/rs.3.rs-226857/v1 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape A 1.8-fold drop in FRNT50 for B.1.351 was observed in 44 sera collected between 1 and 301 post-infection. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 pmid:33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 3.2x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing] Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 6.3x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Encouragingly, we find that the majority of T cell responses in recipients of two doses of the BNT162b2 vaccine are generated by epitopes that are invariant between the [wildtype] and two of the current variants of concern (B.1.1.7 and B.1.351). In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals and recipients of a only a single dose of mRNA vaccine – heterotypic neutralization dropped to negligible levels, particularly against B.1.351. Skelly 2021 https://doi.org/10.21203/rs.3.rs-226857/v1 doi:10.21203/rs.3.rs-226857/v1 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The neutralizing activity of 16/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.351, with similar results for the live virus. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.351. We observed an increase (relative to D614G) in binding of soluble ACE2 to B.1.351, and to a much gearter extent to B.1.1.7, which both carry the N501Y mutation (see Fig 3). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Sera from individuals who have been infected with Delta does not have strong neutralising activity against Beta. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 8 for B.1.351 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 pmid:33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Pseudotype lentivirus for the full B.1.351 Spike variant list shows increase affinity for ACE2 as measured by IC50. This is in contrast to B.1.1.7 which showed no major change, indicating that the shared N501Y mutation is the driver of affinity change, attentuated in the B.1.1.7 mutatioon set, but maintained in the B.1.351 lineage. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 8.2x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.351 pseudotyped virus model ablates neutralization by RBD-directed mAbs CB6, 4-20, 2-4, 2-43, 910-30, 2-302-15, LY-Cov555, C121. B.1.351 pseudotyped virus model severely impairs neutralization by RBD-directed mAb 1-20. B.1.351 pseudotyped virus model impairs neutralization by RBD-directed mAb REGN10933. B.1.351 pseudotyped virus model ablates neutralization by N-terminal-domain-directed mAbs 5-24, 4-8, 4A8, 4-19. B.1.351 pseudotyped virus model severely impairs neutralization by N-terminal-domain-directed mAb 2-17. B.1.351 pseudotyped virus model impairs neutralization by N-terminal-domain-directed mAb 5-7. PG: Live virus data for the same mAbs is similar, but 1-20 becomes severally impaired, REGN10933 activity is ablated, and Brii-196 becomes impaired. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against Beta. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type). Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 pmid:33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 pmid:33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v2 reduced 7.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms had mean ~6x reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR16m molecule had a 99.7x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR16m molecule had a 6.7x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with all key mutations from B.1.351 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting some synergy between the mutations to decrease cell entry fitness (i.e. cell entry is liklely not the driver of this lineage's dominance). Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,23060,23061,23062,23063,22810,22811,22812,22813,22813,23012,23399,23401,23402,23403 L18F,D80A,D215G,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The most significant loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against authentic B.1.351 lineage virus (9.2-fold). Neutralization against 10 convalescent plasma was poorer (18.7x). Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks. Meister 2021 https://doi.org/10.1093/infdis/jiab260 doi:10.1093/infdis/jiab260 pmid:33993274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication] Ribas Freitas 2021 https://doi.org/10.1101/2021.04.13.21255281 doi:10.1101/2021.04.13.21255281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 pmid:33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525 L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the Parana state of Brazil, patients aged 20-29 years experienced a tripling of their case fatality rate (CFR), from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling comparing February to January in 2021. Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil. [this is somewhat indirect evidence that assume greatly increasing proportion of P.1 cases in March (70%) compared to February, but the first official ID of P.1 in Parana state (Feb 16th) may be due to testing procedures rather than actual prevalence] Santos de Oliviera 2021 https://doi.org/10.1101/2021.03.24.21254046 doi:10.1101/2021.03.24.21254046 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22915,22916,22917,23060,23061,23062,23063,23521,23522,23524,23525 L18F,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.52C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 (Pfizer) vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains. Mallm 2021 https://doi.org/10.1101/2021.04.27.21254849 doi:10.1101/2021.04.27.21254849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1, Delta (B.1.617.2) shows mean 2.1x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Relative to B.1, Delta (B.1.617.2) shows 3.64x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,22915,22916,22917,23012,23399,23401,23402,23403 T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this lineage defining mutation combination from B.1.617.3 conferred a ~4.5x infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,22915,22916,22917,23012,23399,23401,23402,23403 T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this lineage defining mutation combination from B.1.617.3 conferred a ~11.8x drop in neutralization (NT50) [suggesting role for T19R and T95I in half the sera]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,22915,22916,22917,23012,23399,23401,23402,23403 T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this lineage defining mutation combination from B.1.617.3 increased syncytium formation ~2.3x. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21846,23399,23401,23402,23403 T19R,T95I,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23604,23399,23401,23402,23403,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,P681R,D614G,D614G,D614G,D614G,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4.5x cleavage of S2 relative to WA1 (D614G) wildtype by Delta (B.1.617.2) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~3.5x for closely related Kappa B.1.617.1 also with P681R at the cleavage site). Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.617.1-v1 ('Kappa') reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. [Mutation list in publication appears to contain a typo with R158del instead of R158G] Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 4.0x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Modelling the Delta variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increased 11x relative to wild type (15.3 vs 1.4). [del ~157 truncated due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a coinfection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant. Liu 2021 https://doi.org/10.1101/2021.08.12.456173v3 doi:10.1101/2021.08.12.456173v3 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.020x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 2.6x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.10x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,24410 T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D950N NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In primary human airway epithelial cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 1.9x relative to wild type (2.7 vs 1.4). This is the Delta variant with the P681R furin cleavage site mutation absent. [del ~157 truncated due to ambiguity] Liu 2021 https://doi.org/10.1101/2021.08.12.456173v3 doi:10.1101/2021.08.12.456173v3 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Plasma neutralizing activity was also assessed against SARS-CoV-2 Delta, Omicron BA.1, BA.2 and BA.4/5 variants using viruses pseudotyped with appropriate variant spikeproteins. Delta breakthrough infection resulted in 15-fold increased neutralizing titers. Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Delta neutralizing antibodies is 0.872x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Delta neutralizing antibodies is 0.952x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Plasma neutralizing activity in 49 participants was measured using HIV-1 pseudotyped with the 100 WT SARS-CoV-2 spike protein. Delta breakthrough infection resulted in 11-fold increased geometric mean half-maximal neutralizing titer (NT50). Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Delta Variant B.1.617.2 RBD or w.t. SARS-CoV-2 RBD with nearly equal potency determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 507 pM for binding to the Delta B.1.617.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 pmid:34437521 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 pmid:34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 pmid:34289274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.92x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021 https://doi.org/10.15585/mmwr.mm7034e3 doi:10.15585/mmwr.mm7034e3 pmid:34437519 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role. Tang 2021 https://doi.org/10.1101/2021.08.11.21261885 doi:10.1101/2021.08.11.21261885 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). Chia 2021 https://doi.org/10.1101/2021.07.28.21261295 doi:10.1101/2021.07.28.21261295 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy The incidence rate of Covid-19 during the Delta-dominant period (Jul-Aug 2021) was lower for late vaccinated (49.0/1000 person-years) [formerly placebo] versus early vaccinated (77.1/1000 person-years) participants in the Moderna mRNA-1273 Phase 3 trials, representing a 36.4% VE reduction (95% CI 17.1%-51.5%). There were fewer severe Covid-19 cases in the late group (6; 6.2/1000 person-years) than early (13; 3.3/1000 person-years), representing a 46.0% reduction (95% CI −52.4%-83.2%). Three Covid-19 related hospitalizations occurred with two resulting deaths in the early group. Baden 2021 https://doi.org/10.1101/2021.09.17.21263624 doi:10.1101/2021.09.17.21263624 pmid:34611666 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccination of health care workers in Delhi was started in early 2021, with the ChdOx-1 (Astra Zeneca) vaccine. Surveillance has suggested B.1.1.7 dominance in the Delhi area during early 2021, with growth of B.1.617 since March 2021. During the wave of infections during March and April an outbreak of SARS-CoV-2 was confirmed in 33 vaccinated staff members at a single tertiary centre (age 27-77 years). Sequencing revealed that 16/33 were B.1.617.2, with a range of other B lineage viruses including B.1.1.7 for the rest except one A lineage case. Importantly no severe cases were documented in this event. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death. 2021 https://doi.org/10.1503/cmaj.211248 doi:10.1503/cmaj.211248 pmid:34610919 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.2 aka Delta) showed a 2.34x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance. Twohig 2021 https://doi.org/10.1016/S1473-3099(21 doi:10.1016/S1473-3099(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Denmark, for the period Jan 1 to Jun 27, 2021, Delta variant was associated with increased an risk ratio of 2.83 [95% CI 2.02–3.98] for hospitalization. Bager 2021 https://doi.org/10.1016/S1473-3099(21 doi:10.1016/S1473-3099(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.89x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Delta Molnupiravir (MK-4482) had ~4x fold drop. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 pmid:35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Case 62541 cluster in Singapore included a fully vaccinated nurse 2 months post-vaccine [likely Pfizer based on dates and supply], and a doctor of unknown vaccine status. This cluster was caused by a B.1.617.2 virus [via crossreference to Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Delta (B.1.617.2) has an IC50 fold change of 46.5x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Delta (B.1.617.2) has an IC50 fold change of 0.15x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Delta (B.1.617.2) has an IC50 fold change of 0.57x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Delta (B.1.617.2) has an IC50 fold change of 0.87x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Delta (B.1.617.2) variant is 0.6x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21618,23399,23401,23402,23403 T19R,D614G,D614G,D614G,D614G NC_045512.2:g.56C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21627 T22I NC_045512.2:g.65C>T YP_009724390.1:p.Thr22Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain, frequently observed in various human infection lineages, reduces the tropism of SARS-CoV-2 in F81 (cat kidney, Felis catus) and BHK-21 (golden hamster kidney, Mesocricetus auratus) cell line cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21648 T29I NC_045512.2:g.86C>T YP_009724390.1:p.Thr29Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21717,21762,21763,21764,21765,21766,21766,21761,23012,23399,23401,23402,23403,23593,23593,24224 Q52R,H69del,H69del,H69del,H69del,H69del,H69del,V70del,E484K,D614G,D614G,D614G,D614G,Q677H,Q677H,F888L NC_045512.2:g.155A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.525 reduced 4.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21717,23012,23593,23593,24224 Q52R,E484K,Q677H,Q677H,F888L NC_045512.2:g.155A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The B.1.525 appears to have poor transmissibility when in competition with B.1.1.7 and other circulating strains in Denmark (early 2021). Albertsen 2021 https://www.covid19genomics.dk/2021-05-08_data-overview.html#b1525 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21752,21752 W64R,W64R NC_045512.2:g.190T>A,NC_045512.2:g.190T>C YP_009724390.1:p.Trp64Arg,YP_009724390.1:p.Trp64Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21759 H66R NC_045512.2:g.197A>G YP_009724390.1:p.His66Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent, especially on a D614 wildtype background. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761 H69del,H69del,H69del,H69del,H69del,H69del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduces neutralization by structurally unmapped mAb COVA1-21 (cluster XI). Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761 H69del,H69del,H69del,H69del,H69del,H69del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding No notable change in neutralization efficiency, despite N439K by itself showing a ~2x decrease on average in 16 health workers' convalescent sera. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761 H69del,H69del,H69del,H69del,H69del,H69del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This deletion outside the receptor binding domain in pseudotyped VSV promoted the capacity of pseudotyped VSV to transduce black flying fox (Pteropus alecto) kidney PabKi.1 cells (17.8%) to a level twice that of human epithelial-like Huh-7 cells (9.8%) Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761 H69del,H69del,H69del,H69del,H69del,H69del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization activity of almost all convalescent sera tested decreased ~2x. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761 H69del,H69del,H69del,H69del,H69del,H69del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization activity of convalescent sera tested decreased ~2x with this B.1.1.7 pseudotyped virus. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761 H69del,H69del,H69del,H69del,H69del,H69del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761 H69del,H69del,H69del,H69del,H69del,H69del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Neutralization activity of almost all Moderna Phase 1 sera tested actually *increased*. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761 H69del,H69del,H69del,H69del,H69del,H69del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761 H69del,H69del,H69del,H69del,H69del,H69del,V70del NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence The delH69/V70 enhances viral infectivity, indicating its effect on virus fitness is independent to the N501Y RBM change [with which it is found in lineage B.1.1.7] Possibly arisen as a result of the virus evolving from immune selection pressure in infected individuals and possibly only one chronic infection in the case of lineage B.1.1.7. Kemp 2020 https://doi.org/10.1101/2020.12.14.422555 doi:10.1101/2020.12.14.422555 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron (a.k.a. B.1.1.529) Spike pseudotyped VSV and Vero E6 cells has somewhat reduced neutralization (2.7x) vs wild type with monoclonal antibody Sotrovimab (a.k.a. VIR-7831). [delins at 214 omitted for syntax compatibility] Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron breakthrough infection after 3-dose vaccination resulted in a further 3.5-fold and 2.9-fold increase of Omicron BA.1 and BA.2 neutralizing titers. Omicron BA.4/5 showed the highest neutralization resistance of all variants tested, resulting in low geometric mean neutralizing titers in plasma samples obtained after the second vaccine dose (NT50=72). Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Delta variant and was used to determine neutralizing antibodytitres. There was a 24.63x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 4.21x fold increase in antibody response pre-reinfection. There was a 39.27x fold increase in antibody response during reinfection. Shete 2022 https://doi.org/10.1101/2022.05.12.491584 doi:10.1101/2022.05.12.491584 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against B.1 variant and was used to determine neutralizing antibodytitres. There was a 6.76x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 2.06x fold increase in antibody response pre-reinfection. There was a 8.18x fold increase in antibody response during reinfection. Shete 2022 https://doi.org/10.1101/2022.05.12.491584 doi:10.1101/2022.05.12.491584 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron B.1.1.529 (BA.1) neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Omicron BA.1 variant is 1.0x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigms’ ACE-2 variant LVE/STR chimera binds to SARS-2 Omicron variant B.1.1.529 spike protein trimer with high affinity. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Omicron BA.1 has an IC50 fold change of 0.38x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 73 pM for binding to the Omicron B.1.1.529. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron (B.1.1.529 [BA.1]) have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding All 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 729 NT50. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 pmid:35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding All 10 individuals with 3 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 3319 NT50. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 pmid:35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.1 has an IC50 fold change of 0.30x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Omicron BA.1 has an IC50 fold change of 1.26x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Omicron variant and was used to determine neutralizing antibodytitres. There was a 114.84x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 6.61x fold increase in antibody response pre-reinfection. There was a 1194.9x fold increase in antibody response during reinfection. Shete 2022 https://doi.org/10.1101/2022.05.12.491584 doi:10.1101/2022.05.12.491584 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.1 has an IC50 fold change of 0.08x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.3 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.3 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604 H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was somewhat lower against B.1.1.7 in sera tested from most of the 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604 H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.7 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2489. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.1.7 sample. Contrast this with 1.3-fold reduction for just the pseudovirus combination of 'key' B.1.1.7 mutation N501Y. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 pmid:33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,22920 H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing moderate decrease in infection rate amongst the cells, significantly lower than the deletion or Y453F alone, or their combination, suggesting a synergistic effect on poorer human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,22920 H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild to modest decrease in infection rate amongst the cells, suggesting a net mild negative effect on human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,22920 H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, much closer to D614G activity level than Y453F alone, suggesting compensatory effects between the deletion and the mutation in human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,22920,23399,23401,23402,23403,25249,25249,25249 H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F,D614G,D614G,D614G,D614G,M1229I,M1229I,M1229I NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.298 virus has reduced neutralization activity vs wild type: 1.4x (30 sera Pfizer median 9 days post 2nd dose) and 1.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,22920,25249,25249,25249 H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F,M1229I,M1229I,M1229I NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Lentiviral pseudotyped with the key mutations from Mink Cluster 5 was neutralized more easily than D614G in 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,22920,25249,25249,25249 H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F,M1229I,M1229I,M1229I NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with all key mutations from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (~50%) decrease in infection rate amongst the cells, suggesting that this anthropozoonotic event is driven by other factors at the expense of human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,22920,25249,25249,25249 H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F,M1229I,M1229I,M1229I NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells, markedly higher infectivity than either mutation alone, suggesting a synergistic net neutral effect on human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.7+E484K reduced 2.8x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Compare with 1.2x reduction for B.1.1.7 without E484K. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization capacity GMT of 27 subjects' sera post-infection was markedly worse against B.1.1.7 + E484K than the lineage alone, with a 11.4x drop. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence In comparison of B.1.1.7 lineage (193 cases) vs. 'wildtype' (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo. van Loon 2021 https://doi.org/10.1101/2021.04.15.21255389 doi:10.1101/2021.04.15.21255389 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence A higher proportion of cases infected with the B.1.1.7 variant were hypoxic on admission compared to other variants (70.0% vs 62.5%, p=0.029), in London between March 13th 2020 and February 17th 2021 (400 B.1.1.7 cases out of 1470 total sequenced). Snell 2021 https://doi.org/10.1101/2021.03.16.21253377 doi:10.1101/2021.03.16.21253377 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x). PG: these effects are laregly missing in the deletion-alone data Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This mutation combination causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, moreso than this combination with the addition of P681H. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020. Possible reinfections were identified in 249 (0.7% [95% CI 0.6-0.8]) of 36509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Graham 2021 https://doi.org/10.1016/s2468-2667(21 doi:10.1016/s2468-2667(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 https://doi.org/10.1016/S0140-6736(21 doi:10.1016/S0140-6736(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 pmid:33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion). Marquez 2021 https://doi.org/10.1017/ice.2021.195 doi:10.1017/ice.2021.195 pmid:33934744 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 https://doi.org/10.1016/S0140-6736(21 doi:10.1016/S0140-6736(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 pmid:33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 pmid:33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 pmid:33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Second infection in December 2020 with B.1.1.7 after April 2020 initial infection with B.2 in a 78-year-old man with a history of Type 2 diabetes mellitus, diabetic nephropathy on hemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnea, ischemic heart disease, with no history of immunosuppression. Harrington 2021 https://doi.org/10.1093/cid/ciab014 doi:10.1093/cid/ciab014 pmid:33421056 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 pmid:33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Alpha (B.1.1.7) variant is 1.0x fold the wildtype in 42 COVI. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.1.7. We observed a dramatic increase (relative to D614G) in binding of soluble ACE2 to B.1.1.7, and to a lesser extent to B.1.351, which both carry the N501Y mutation (see Fig 3). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 https://doi.org/10.1016/S0140-6736(21 doi:10.1016/S0140-6736(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 https://doi.org/10.1016/S0140-6736(21 doi:10.1016/S0140-6736(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks. Meister 2021 https://doi.org/10.1093/infdis/jiab260 doi:10.1093/infdis/jiab260 pmid:33993274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively. Schuit 2021 https://doi.org/10.1093/infdis/jiab171 doi:10.1093/infdis/jiab171 pmid:33822064 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021 https://doi.org/10.1136/bmj.n1088 doi:10.1136/bmj.n1088 pmid:33985964 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021 https://doi.org/10.1016/j.cmi.2021.05.007 doi:10.1016/j.cmi.2021.05.007 pmid:33984489 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 pmid:34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Alpha (B.1.1.7) has an IC50 fold change of 1.19x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Alpha Molnupiravir (MK-4482) had ~2.75x fold drop. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 pmid:35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The sera of 16 individuals with time course collection was evaulated against VSV pseudotypes: neutralized D614G at week 2, whereas B.1.1.7 started to be neutralized at week 3, although less efficiently than D614G. B.1.1.7 and D614G strains were similarly neutralized at week 4 (1 week after booster dose). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 pmid:33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 pmid:33772577 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the 47D10. Alpha (B.1.1.7) has an IC50 fold change of 0.40x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~2.5x cleavage of S2 relative to WA1 (D614G) wildtype by Alpha variant variant as measured by mass spectrometry of Vero-TMPRSS culture. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.39x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape NTD-specific nAbs showed a substantial (3-450x) decrease in neutralization potency against the recently reported highly transmissible B.1.1.7 variant of concern, whereas RBD-specific nAbs were either unaffected or showed lower decreases in potency. Graham 2021 https://doi.org/10.1016/j.immuni.2021.03.023 doi:10.1016/j.immuni.2021.03.023 pmid:33836142 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects ~20x resistence to mAb CQ038 by B.1.1.7 pseudotyped virus Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralizing antibody titers of 2/20 (10%) samples showed >10x reduction (sera collected ~1mo post Jan 2020 first wave in China). Neutralizing antibody titers of 8/20 samples (40%) decreased below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China). Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM for binding to the Alpha B1.1.7. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 2.6x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Lessens the potency of mAbs COVA2-17 (~5x, similar to N501Y alone), COVA1-12 (~11x) and COVA1-21 (>100x), which do not compete allosterically. Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.7 pseudotyped virus model impairs binding by RBD-directed mAb 910-30. B.1.1.7 pseudotyped virus model abolishes N-terminal-domain-directed mAbs 5-24, 4-8, and 4A8. B.1.1.7 pseudotyped virus model impairs binding by N-terminal-domain-directed mAbs 2-17, 4-19, 5-7. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%). Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Modelling the Alpha variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 3.9x relative to wild type (5.4 vs 1.4). This is less efficient than Delta (11x vs wildtype using a P681R mutation instead). [del ~144 changed due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a co-infection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant. Liu 2021 https://doi.org/10.1101/2021.08.12.456173v3 doi:10.1101/2021.08.12.456173v3 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 pmid:34289274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization assays of B.1.1.7 virus showed a reduction of 2.5-fold (14 days post 2nd dose AstraZeneca, n=15), 2.1-fold (28 days post 2nd dose AstraZeneca, n=10), and 3.3-fold (7-17 days post 2nd dose Pfizer-BioNTech, n=25). [D1119H was included in the original paper, assumed typographical error and changed to D1118H] Supasa 2021 https://doi.org/10.1016/j.cell.2021.02.033 doi:10.1016/j.cell.2021.02.033 pmid:33743891 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 1 (B.1.1.7) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2. Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.7 virus has reduced neutralization activity vs wild type: 2.1x (30 sera Pfizer median 9 days post 2nd dose) and 2.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Note that Y145del was actually noted in the paper as the effect of their DNA construct, but this is equivalent at the protein level to the more commonly annotated Y144del. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure CryoEM analysis of B.1.1.7 demonstrates an increased propensity for 'up', receptor accessible conformation of the Spike protein trimer. Cai 2021 https://doi.org/10.1101/2021.04.13.439709 doi:10.1101/2021.04.13.439709 pmid:33880477 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Alpha Variant B.1.1.7 RBD significantly better than GenScript IgG FL18-740 w.t. ACE-2 mAB. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy NVX-CoV2373 [Novavax] vaccine in phase 3 trial was 89.7% (95% CI, 80.2-94.6) effective in preventing COVID-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8-99.5) and 86.3% (71.3-93.5) against the prototype strain and B.1.1.7 variant, respectively. Heath 2021 https://doi.org/10.1101/2021.05.13.21256639 doi:10.1101/2021.05.13.21256639 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Live virus was tested ex vivo in reconstituted brochial epithelium, and out competed wild type. Touret 2021 https://doi.org/10.1101/2021.03.22.436427 doi:10.1101/2021.03.22.436427 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 1.7x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) clinical indicators After adjusting for the age factor, in a prospective Chinese cohort study B.1.1.7 variant infection (compared to B.1.140) was the risk factor for C-reactive protein (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), Serum amyloid A (0.011, 5.031, [1.459, 17.354]), Creatine Kinase (0.034, 4.34, [0.05, 0.91]), CD4+ T lymphocyte (0.029, 3.31, [1.13, 9.71]), and Ground Glass Opacity (0.005, 5.418, [1.656, 17.729]) Song 2021 https://doi.org/10.1101/2021.05.04.21256655 doi:10.1101/2021.05.04.21256655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 pmid:34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) aerosolization Alpha variant cases in a large campus study showed fine-aerosol shedding amongst unmasked participants remained significantly greater for alpha variant infections (18-fold, 95% CI, 3.4 to 92-fold) after adjusting for the increased viral RNA in MTS and saliva, the number of coughs during sampling sessions, and symptom. After controlling for the effect of masks and numbers of coughs during sampling, alpha variant infection was associated with a 100-fold (95% CI, 16 to 650-fold) increase in coarse- and a 73-fold (95% CI, 15 to 350-fold) increase in fine-aerosol RNA shedding. Adenaiye 2021 https://doi.org/10.1093/cid/ciab797 doi:10.1093/cid/ciab797 pmid:34519774 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 pmid:33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We observed a sharp decline in cases when ∼50% of the elderly population was 2 weeks beyond their first vaccination dose and at a time point during which the B.1.1.7 variant gained transmission dominance. In support of this finding, it was suggested that, after the first vaccination dose, more than 70% of patients develop neutralization antibodies,15 and the vaccine efficiency can reach 85%. Munitz 2021 https://doi.org/10.1016/j.xcrm.2021.100264 doi:10.1016/j.xcrm.2021.100264 pmid:33899031 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.44x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 pmid:33972942 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events First documented cases of domestic cat and dog infections with the B.1.1.7 strain. Hamer 2021 https://doi.org/10.1111/tbed.14122 doi:10.1111/tbed.14122 pmid:33955193 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy , Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.1.7 lineage effectiveness was observed as 29.5% (95% CI [22.9,35.5]) against infection, and 54.1% against severe/critical/fatal disease (95% CI [26.1-71.9]). Two weeks or more after 2nd dose, effectiveness climbed to 89.5% [85.9,92.3] against infection, and 100% against severe/critical/fatal disease (95% CI [81.7,100]). , Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24506 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,S982A NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Lilly's LY-CoV16 showed marked reduction in neutralization of B.1.1.7. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 pmid:33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Sera neutralized the B1.1.7 isolate with a lower potency (2-fold; 95% CL: 1.5 – 3-fold), and those with the lowest homotypic neutralizing potency had undetectable heterotypic potency (2/25). Skelly 2021 https://doi.org/10.21203/rs.3.rs-226857/v1 doi:10.21203/rs.3.rs-226857/v1 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23709,23604,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,T716I,P681H,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific replication effects In this report, by using a lower infectious dose, we demonstrate that B.1.1.7 (cultured sample Hong Kong/HKPU-00015/2021) exhibits higher infectivity and/or replication efficiency in the nasal epithelium. (Hamster model of infection) Mok 2021 https://doi.org/10.1101/2021.04.19.440414 doi:10.1101/2021.04.19.440414 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 pmid:33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks. Munitz 2021 https://doi.org/10.1016/j.xcrm.2021.100264 doi:10.1016/j.xcrm.2021.100264 pmid:33899031 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 'wild type' SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples. Couzens 2021 https://doi.org/10.1101/2021.04.02.21254832 doi:10.1101/2021.04.02.21254832 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Based on 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020, Rt of B.1.1.7 was 1.35x (95% CI 1.02-1.69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Graham 2021 https://doi.org/10.1016/s2468-2667(21 doi:10.1016/s2468-2667(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change. Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively. Roquebert 2021 https://doi.org/10.1101/2021.03.19.21253971 doi:10.1101/2021.03.19.21253971 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036). Song 2021 https://doi.org/10.1101/2021.05.04.21256655 doi:10.1101/2021.05.04.21256655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021 https://doi.org/10.48550/arXiv.2104.05560 doi:10.48550/arXiv.2104.05560 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. Graham 2021 https://doi.org/10.1016/s2468-2667(21 doi:10.1016/s2468-2667(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The mortality hazard ratio associated with infection with [B.1.1.7] compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community (54906 matched pairs of participants who tested positive for SARS-CoV-2 in pillar 2 between 1 October 2020 and 29 January 2021). In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases. Challen 2021 https://doi.org/10.1136/bmj.n579 doi:10.1136/bmj.n579 pmid:33687922 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio 341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). Frampton 2021 https://doi.org/10.1016/s1473-3099(21 doi:10.1016/s1473-3099(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization capacity GMT of 27 subjects' sera post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies. Muik 2021 https://doi.org/10.1126/science.abg6105 doi:10.1126/science.abg6105 pmid:33514629 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 pmid:33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 20/29 sera after the first dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 variant of 3.2 ± 5.7. After the second dose, the GMT was markedly increased compared with the first-dose titres, with a fold change of 1.9 ± 0.9 (mean ± s.d.). Neutralization GMT of 27 subjects post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 pmid:33658326 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49) Buchan 2021 https://www.medrxiv.org/content/10.1101/2021.03.31.21254502v1 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking VSV pseudotype B.1.1.7 showed no significant difference in cell entry relative to wild type in 6 cell lines. Cell fusion proficiency was unchanged. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021 https://doi.org/10.1038/s41586-021-03426-1 doi:10.1038/s41586-021-03426-1 pmid:33723411 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants. Lindstrøm 2021 https://doi.org/10.1101/2021.03.29.21254122 doi:10.1101/2021.03.29.21254122 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 ('UK variant'). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H. Ratcliff 2021 https://doi.org/10.1101/2021.02.24.21251989 doi:10.1101/2021.02.24.21251989 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, but to a smaller extent than N501Y and the deletion alone. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Slight neutralization improvement on average in 16 health workers' convalescent sera. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding These key B.1.1.7 mutations as a combination neutralized slightly less well than D614G and this was noticeable in the lack of sera with high neutralizing titer for the viruses across 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604 H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,23399,23401,23402,23403,22915,22916,22917 H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 17.2x-fold lower (95% CI: 0.6x-0.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,23399,23401,23402,23403,22915,22916,22917 H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 13.0-fold lower (95% CI: 4.2x-4.6x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,22810,22811,22812,22813,22813,23009,23010,23012,23013 H69del,H69del,H69del,H69del,H69del,H69del,K417N,K417N,K417N,K417N,K417N,E484A,E484A,E484A,E484A NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Ontario, using a retrospective matched case (age, gender and onset date) study of 6,312 Omicron cases vs 8,875 Delta, the adjusted risk of hospitalization or death was 54% lower (HR=0.46, 95%CI: 0.27, 0.77) among Omicron cases, after adjusting for vaccination statis and time since 2nd shot. The ratio for >60yo was 0.55 (95%CI: 0.28-1.06), and <60yo was 0.30 (95%CI: 0.16-0.57). Ulloa 2021 https://doi.org/10.1101/2021.12.24.21268382 doi:10.1101/2021.12.24.21268382 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21765,21766,21766,23009,23010,23012,23013 H69del,H69del,H69del,H69del,H69del,H69del,E484A,E484A,E484A,E484A NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection, evidenced by a reinfection hazard ratio of 2.39 (CI95: 1.88-3.11) relative to primary infection in the initial part of South Africa's 4th covid-19 wave (November 2021). In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. [minimal variant signature for Omicron (B.1.1.529) used based on H69del PCR dropout observed in November 2021 coincident with the rise of Omicron] Pulliam 2021 https://doi.org/10.1101/2021.11.11.21266068 doi:10.1101/2021.11.11.21266068 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800 D80N NC_045512.2:g.238G>A YP_009724390.1:p.Asp80Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800 D80Y NC_045512.2:g.238G>T YP_009724390.1:p.Asp80Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This AA substitution outside the receptor binding domain in pseudotyped VSV promoted a 7.2% transduction rate in golden hamster cells, which was higher than that of human epithelial-like Huh-7 cells (6.6%). Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800,22188,22206,22597,22599,23012,23521,23522,23524,23525,23604 D80Y,I210del,D215G,R346K,R346K,E484K,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.238G>T,NC_045512.2:g.629_631del,NC_045512.2:g.644A>G,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp80Tyr,YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against A.VOI.V2 (first identified in Angola) reduced 8.0x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion One individual of 30 in the study, with HLA supertype HLA*A24:02, had a linear epitope that overlaps this variant of concern. Redd 2021 https://doi.org/10.1101/2021.02.11.21251585 doi:10.1101/2021.02.11.21251585 pmid:33594378 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 pmid:34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abolishes neutralizing activity of N-terminal-domain-directed mAb 4-19. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2:g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated that there is no free energy change (ddG) for this variant (i.e. same stability as wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In an Ontario long term care facility, cumulatively, weaker BNT162b2 vaccine stimulation, age/comorbidities, produced a ∼130-fold reduction in apparent neutralization titers in mean 88yo LTCH residents against Beta (B.1.351), relative to staff vaccinees against D614G wild type. 37.9% of 116 two-dose-mRNA-vaccinated residents had undetectable neutralizing antibodies to B.1.351. mRNA-1273 vaccinee sera displayed ~2 better neutralization than BNT162b2. [common defining B.1.351 mutations noted, as the manuscript does not provide details] Abe 2021 https://doi.org/10.1101/2021.08.06.21261721 doi:10.1101/2021.08.06.21261721 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, 7 of 15 neutralized this B.1.351 pseudotype that includes the L242del, and only one had titers above 100. Only one of the 15 sera achieved 80% neutralization. [compare to 5 and 1 for pseudotype without the deletion] Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 pmid:33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.351 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 71%, Day 209 54%. Detectable antibodies against B.1.351 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 79%, Day 209 58%. Detectable antibodies against B.1.351 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 63%, Day 43 100%, Day 119 71%, Day 209 79%. Decreased neutralization on some assays was seen especially in those vaccinees tested that were 71+. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 pmid:34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~10-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~3 fold without the deletion] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were significant, but ~500x weaker than in previously infected patients after first dose. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 pmid:33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 pmid:33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A two-dose regimen of (AstraZeneca) ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, vaccine efficacy against severe Covid-19 is undetermined. Madhi 2021 https://doi.org/10.1101/2021.02.10.21251247 doi:10.1101/2021.02.10.21251247 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) humoral response durability In a prospective study of 107 hospitalized patients, decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7 and P.1 variants for at least 6 months (last of two samples taken) in patients previously hospitalized for COVID-19. A weaker protection was however observed for the B.1.351 variant. Betton 2020 https://doi.org/10.1093/cid/ciab308 doi:10.1093/cid/ciab308 pmid:33851216 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 pmid:33972942 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Beta (B.1.351) has an IC50 fold change of 0.13x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination. Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 34 convalescent cases 4–9 weeks following infection in June 2020, before the emergence of B.1.1.7, neutralization titers against B.1.351 were, on average, 13.3-fold reduced compared with an early Victoria sample (p < 0.0001). Significantly, 18 of 34 samples failed to reach 50% neutralization at a plasma dilution of 1:20, with a number showing a near total reduction of neutralization activity. In 13 convalescent cases 4–9 weeks following infection with B.1.1.7, neutralization titers against B.1.351 were, on average, 3.1-fold reduced compared with an early Victoria sample (p < 0.0001). Zhou 2021 https://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 pmid:33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Beta (B.1.351) variant is 0.4x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Unlike wild type or B.1.1.7, B.1.351 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. PG: The virus used in these expriments has a non-typical deletion+sub in the 242 region. Montagutelli 2021 https://doi.org/10.1101/2021.03.18.436013 doi:10.1101/2021.03.18.436013 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v3 reduced 8.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The B.1.351 variant constellation causes an ∼20-fold increase in affinity for ACE2 compared with Wuhan RBD, which may influence transmissibility. Zhou 2021 https://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 pmid:33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001). Zhou 2021 http://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 pmid:33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~6x cleavage of S2 relative to WA1 (D614G) wildtype by Beta variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but A701V is downstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Beta (B.1.351) has an IC50 fold change of 0.13x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccine plasma neutralization of B.1.351-spike virus was nominally robust but lower (~3x) than other variants of concern. Liu 2021 https://doi.org/10.1056/NEJMc2102017 doi:10.1056/NEJMc2102017 pmid:33684280 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Testing against B.1.351 the 20 most effective mAbs (19 anti-RBD, 1 anti-NTD) from a screen of 377 against wild type, 4 of 20 antibodies had >10-fold fall in neutralization titers, with most of these showing a complete knockout of activity. This is in line with the key roles of K417, E484, and N501, in particular E484, in antibody recognition of the ACE2 interaction surface of the RBD. Regeneron mAb cocktail: The neutralization of REGN10987 was unaffected by B.1.351, while REGN10933 was severely impaired (773-fold). AstraZeneca mAb cocktail: Neutralization by the AZ pair of antibodies was little affected on B.1.351 compared with Victoria. Zhou 2021 https://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 pmid:33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Beta Molnupiravir (MK-4482) had ~1.75x fold drop. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 pmid:35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.351 v1 virus has reduced neutralization activity vs wild type: 34.5x (30 sera Pfizer median 9 days post 2nd dose) and 27.7x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.351 defining mutations: Significant shift to infection in those without pre-existing conditions (79.6% vs 89% for non-VOC cases). Significant increase in hospitalization rate (19.3% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.3% vs 0.6% for non-VOC cases). PG: seems to be different notations around the LAL deletion, using the minimal shared definition to catch as many as possible. Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 pmid:33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Beta (B.1.351) has an IC50 fold change of 0.88x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Compared to Alpha (B.1.1.7) variant, odds of progressing to severe disease were 1.24-fold (95% CI: 1.11-1.39) higher for Beta. Odds of progressing to critical disease were 1.49-fold (95% CI: 1.13-1.97) higher. Odds of COVID-19 death were 1.57-fold (95% CI: 1.03-2.43) higher. Abu-Raddad 2021 https://doi.org/10.1101/2021.08.02.21261465 doi:10.1101/2021.08.02.21261465 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Beta (B.1.351) has an IC50 fold change of 0.15x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using B.1.351 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 pmid:33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~3-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~10 fold with L242del] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were signficiant, but >100x weaker than in previously infected patients after first dose. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 pmid:33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, one third (5/15) of sera neutralized this B.1.351 pseudotype and only three had ID50 titers above 100. Only two of the 15 sera achieved 80% neutralization. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 pmid:33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence Inoculation with the B.1.351 isolate resulted in lower clinical scores in 6 rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. Our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity. Munster 2021 https://doi.org/10.1101/2021.05.07.443115 doi:10.1101/2021.05.07.443115 pmid:34382034 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission. Yinda 2021 https://doi.org/10.1101/2021.05.05.442780 doi:10.1101/2021.05.05.442780 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 4 health care workers in the 20's and 30's with no underlying conditions and seropositivity or confirmed 2020 SARS-CoV-2 infections were confirmed to have B.1.351 infection during a Februrary 2021 hospital outbreak in Luxembourg. Symptoms were mostly mild on first infection, and milder on second infection. Staub 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.18.2100423 doi:10.2807/1560-7917.ES.2021.26.18.2100423 pmid:33960291 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy During an outbreak of SARS-CoV-2 501Y.V2 in a nursing home, all non-vaccinated residents (5/5) versus half of those fully vaccinated 2-5 weeks prior with BNT162b2 (13/26) were infected. Two of 13 vaccinated versus 4 of 5 non-vaccinated residents presented severe disease. BNT162b2 did not prevent the outbreak, but reduced transmission and disease severity. Among the 13 fully vaccinated residents who were infected, 2 (15.4%) presented with an asymptomatic disease, 9 (69.2%) developed mild to moderate symptoms, and 2 (15.4%) progressed to severe disease with fatal evolution secondary to acute respiratory distress syndrome (ARDS). There was no relationship between anti-S antibody levels at diagnosis and disease severity. Overall, the proportion of residents with severe disease in the non-vaccinated group (4/5) was higher than that in the vaccinated group (2/13). Only 1 vaccinated staff, but 10 unvaccinated were infected in the outbreak (no severe disease). Bailly 2021 https://doi.org/10.1093/cid/ciab446 doi:10.1093/cid/ciab446 pmid:33993228 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.351 v3 virus has reduced neutralization activity vs wild type: 42.4x (30 sera Pfizer median 9 days post 2nd dose) and 19.2x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.351 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. B.1.1.351 variant constellation ablates Class 3 N-terminal domain targeting antibodies COV2-2489 and COV2-2676 (the only two tested). Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351. 2021 https://www.fda.gov/media/146217/download False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.351 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0020 for moderate resistance. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 pmid:33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.351 in 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In a Syrian hamster model, B.1.351 variant virus had >4x reduction in YRNT90 (measure of neutralization) using wild type convalescent sera. PG: Note that exact sequence for B.1.351 used was not disclosed. Cochin 2021 https://doi.org/10.1101/2021.04.19.440435 doi:10.1101/2021.04.19.440435 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 pmid:33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 pmid:33851181 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer Solfrosi 2021 https://doi.org/10.1084/jem.20202756 doi:10.1084/jem.20202756 pmid:33909009 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.351 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the B.1.351 variants used, using the most popular as a stad in] McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H] Supasa 2021 https://doi.org/10.1016/j.cell.2021.02.033 doi:10.1016/j.cell.2021.02.033 pmid:33743891 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding VSV pseudotype B.1.351 showed 7.86-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections). Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.351 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 pmid:33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 pmid:33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccine elicited antibodies neutralized virus with the B.1.351 spike protein had an average 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abrogates Bamlanivimab, Etesevimab, or their combined use neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In one of eight cell lines tested (293T lung cells), a modest increase in cell entry was observed. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking VSV pseudotype B.1.351 showed slight decrease in cell entry relative to wild type in 263T-ACE2 (kidney) cell line, and slight increase in Calu-3 (lung). Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness VSV pseudotype B.1.351 entry mediated by the S proteins of the B.1.351 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.351 lineage effectiveness was observed as 16.9% (95% CI [10.4,23.0]) against infection, and 0% against severe/critical/fatal disease (95% CI [0-19.0]). Two weeks or more after 2nd dose, effectiveness climbed to 75.0% [70.5,78.9] against infection, and 100% against severe/critical/fatal disease (95% CI [73.7,100]). , Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy , Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 pmid:33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Approximately 6-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846 T95I NC_045512.2:g.284C>T YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 65yo female with no severe Covid-19 risk factors tested positive 36 days after second dose of BNT162b2 (Pfizer) vaccine. Presented with fatigue, sinus congestion, and a headache developed; her symptoms plateaued and began to resolve six days later. [Mising genome coverage in regions of Spike covering clinically relevant mutations K417T, L452R, E484K, A701V, D796H, N501Y] Hacisuleyman 2021 https://doi.org/10.1056/NEJMoa2105000 doi:10.1056/NEJMoa2105000 pmid:33882219 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.617.1-v1 ('Kappa') reduced 3.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22317,22319,22320,23399,23401,23402,23403 T95I,D253G,D253G,D253G,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio B.1.526 (Iota) substantially increased IFR in older adults: by 46% (95% CI: 7.4 – 84%) among 45-64 year-olds, 82% (95% CI: 20 – 140%) among 65-74 year-olds, and 62% (95% CI: 45 – 80%) among 75+ during Nov 2020 – Apr 2021, compared to baseline IFR estimated for preexisting variants. [minimum clade defining mutations listed] Yang 2021 https://doi.org/10.1101/2021.08.04.21261596 doi:10.1101/2021.08.04.21261596 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera from vaccinees [ChAdOx1 and BNT162b2 primarily used in UK] shows decreased ability to neutralize B.1.621 compared to first wave virus and Alpha, with a magnitude of change similar to Beta. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against B.1.621. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Sera from individuals who have been infected with Delta does not have strong neutralising activity against B.1.621 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 69 test-positive were Mu. Two dose vaccine efficacy against Mu was 90.4% (73.9-96.5%), one dose VE was 45.8% (0.0-88.9%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 pmid:33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using live B.1.621 virus and a cytopathic effect-based assay, sera from 37 Pfizer/BioNTech BNT162b2 vaccinees collected 10-20 days post-booster showed significantly lower (95) but still 'robust' neutralization than against ancestral B.1 virus (107). Messali 2021 https://doi.org/10.1002/jmv.27247 doi:10.1002/jmv.27247 pmid:34329486 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 7.6x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. [This is a greater reduction than Beta @ 6.3x] Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410 T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 12.4x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. [This is a greater reduction than Beta @ 8.2x] Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403 T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 1.5x-fold lower (95% CI: 0.05x-0.07x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403 T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 4.4-fold lower (95% CI: 4.3x-4.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,23012,23271,23399,23401,23402,23403,23604,23948 T95I,E484K,A570D,D614G,D614G,D614G,D614G,P681H,D796H NC_045512.2:g.284C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2386G>C YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp796His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 51yo female with no severe COVID-19 risk factors tested positive 19 days after second dose of mRNA-1273 (Moderna) vaccine. Presented with sore throat, congestion, and headache developed; the next day she lost her sense of smell. Symptoms resolved over a one week period. Serum obtained 4 days after symptom onset was tested for neutralization against wild-type virus, the E484K mutant, and the B.1.526 variant. It was equally effective against each. These data suggest that the antibody response recognized these variants but was nonetheless insufficient to prevent a breakthrough infection. The virus detected matched neither B.1.1.7 nor B.1.526 VOC strains in wide circulation in New York at the time of infection, though shared some mutations. Hacisuleyman 2021 https://doi.org/10.1056/NEJMoa2105000 doi:10.1056/NEJMoa2105000 pmid:33882219 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,23399,23401,23402,23403 T95I,D614G,D614G,D614G,D614G NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21855 S98F NC_045512.2:g.293C>T YP_009724390.1:p.Ser98Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly enhanced the transduction rate in raccoon dog (Nyctereutes procyonoides) kidney (62.4%) and Rickett’s big-footed bat (Myotis pilosus) kidney (45.0%) cell cultures compared to epithelial-like human Huh-7 cells (38.9%). Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21929 A123S NC_045512.2:g.367G>T YP_009724390.1:p.Ala123Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected in passage with mAb COV2-2489 during alanine mutagenesis antibody mapping experiment. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 pmid:33501445 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21969 C136Y NC_045512.2:g.407G>A YP_009724390.1:p.Cys136Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massively decreases N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21969 C136Y NC_045512.2:g.407G>A YP_009724390.1:p.Cys136Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events These variants dominate in mink infections in North America, sometime supplemented with F486L. The Y453F variant found in other jurisdictions in mink infections is notably absent in North America. 2021 https://doi.org/10.1101/2021.03.18.21253734v3 doi:10.1101/2021.03.18.21253734v3 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected twice in passage with mAb COV2-2489. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 pmid:33501445 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. [PG: This mutation is adjacent to a well known deletion, which may confound the significance of this variant] Lucaci 2021 https://observablehq.com/@aglucaci/sc2-omicron Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Average 2x neutralization efficiency decrease against sera from 26 Phase II trial Covaxin (BBV152) vaccine recipents. Very similar to B.1.1.7 (~2x) in the same study, and the neutralization from 17 sera of natural infections across B1 lineages. Yadav 2021 https://doi.org/10.1101/2021.04.23.441101 doi:10.1101/2021.04.23.441101 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~3.5x cleavage of S2 relative to WA1 (D614G) wildtype by Kappa (B.1.617.1) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~4.5x for closely related Delta B.1.617.2 also with P681R at the cleavage site). Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.617.1-v1 ('Kappa') reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.617.1) showed a 1.79x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cluster of B.1.617[.1] infections related to travel from India to USA, one patient with mild symptoms had received their second dose of Pfizer vaccine more than two weeks before the infection [i.e. vaccine breakthrough]. Verghese 2021 https://doi.org/10.1128/JCM.00741-21 doi:10.1128/JCM.00741-21 pmid:33952596 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1, Kappa (B.1.617.1) shows mean 1.97x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.1) showed a 1.12x increase in binding (KD) relative to D614G, but described as 'not significant'. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Relative to B.1, Kappa (B.1.617.1) shows 5.71x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.617.1) showed a 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Kappa (B.1.617.1) has an IC50 fold change of 80.2x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Kappa (B.1.617.1) has an IC50 fold change of 0.68x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Kappa (B.1.617.1) has an IC50 fold change of 2.3x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Kappa (B.1.617.1) has an IC50 fold change of 0.13x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Omicron BA.2 has an IC50 fold change of 0.09x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Omicron BA.2 variant is 0.8x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.2 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Omicron BA.2 has an IC50 fold change of 0.08x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.2 has an IC50 fold change of 0.07x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.2 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.2 has an IC50 fold change of 0.04x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21974 D138Y NC_045512.2:g.412G>T YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.43 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21977 P139S NC_045512.2:g.415C>T YP_009724390.1:p.Pro139Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2:g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected once in passage with mAb COV2-2676. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 pmid:33501445 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2:g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2:g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990 Y145del,Y145del NC_045512.2:g.432_434del,NC_045512.2:g.432_434del YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990 Y145del,Y145del NC_045512.2:g.432_434del,NC_045512.2:g.432_434del YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient. McCarthy 2021 https://doi.org/10.1126/science.abf6950 doi:10.1126/science.abf6950 pmid:33536258 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990,21993,21995,23012,23399,23401,23402,23403 Y145del,Y145del,H146del,H146del,E484K,D614G,D614G,D614G,D614G NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.436_438del,NC_045512.2:g.436_438del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.His146del,YP_009724390.1:p.His146del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Normalized for particle number, on ACE2.293T cells showed that the B.1.618 spike protein was about as infective as D614G wild type. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21993,21995 H146del,H146del NC_045512.2:g.436_438del,NC_045512.2:g.436_438del YP_009724390.1:p.His146del,YP_009724390.1:p.His146del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient. McCarthy 2021 https://doi.org/10.1126/science.abf6950 doi:10.1126/science.abf6950 pmid:33536258 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21997,21998,21999,22000,22001 K147E,K147E,K147E,K147E,K147E NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2X28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21997,21998,21999,22000,22001 K147E,K147E,K147E,K147E,K147E NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21998 H146Y NC_045512.2:g.436C>T YP_009724390.1:p.His146Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in 4A8 monoclonal antibody EC50 (i.e. ablated recognition), but much milder effect on mAbs within antigenic supersite 'i' McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22001 K147Q NC_045512.2:g.439A>C YP_009724390.1:p.Lys147Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22002 K147T NC_045512.2:g.440A>C YP_009724390.1:p.Lys147Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22002 K147T NC_045512.2:g.440A>C YP_009724390.1:p.Lys147Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massively decreases N terminal domain antigen recognition by supersite i mAbs S2M28, S2X28, S2X333, 4A8 (but not S2L28). McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22003 K147N NC_045512.2:g.441A>T YP_009724390.1:p.Lys147Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22005 N148S NC_045512.2:g.443A>G YP_009724390.1:p.Asn148Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong positive selection (up to 72% of supernatant sequences) under six rounds of COV47 convalescent plasma passage Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22010 K150E NC_045512.2:g.448A>G YP_009724390.1:p.Lys150Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22010 K150E NC_045512.2:g.448A>G YP_009724390.1:p.Lys150Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong positive selection (up to 40% of supernatant sequences) under three rounds of COV47 convalescent plasma passage Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22011 K150T NC_045512.2:g.449A>C YP_009724390.1:p.Lys150Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 22% of supernatant sequences) after COV47 convalescent plasma assay Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22011 K150R NC_045512.2:g.449A>G YP_009724390.1:p.Lys150Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 18% of supernatant sequences) under two rounds of COV47 convalescent plasma passage Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22016,22016 W152R,W152R NC_045512.2:g.454T>A,NC_045512.2:g.454T>C YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22016,22016 W152R,W152R NC_045512.2:g.454T>A,NC_045512.2:g.454T>C YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For NTD-binding neutralizing antibody ADI-56479 this mutation causes a 1000x drop in neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22018 W152C NC_045512.2:g.456G>T YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The W152C mutation reduced recognition of six NTD neutralizing mAbs, including a complete loss of binding for two of them, with a complementary pattern to that observed for S13I (also found in lineage B.1.427/B.1.429) out of 11 neutralizing mAbs evaluated. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22018 W152C NC_045512.2:g.456G>T YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Pseudoviruses carrying the W152C mutation demonstrated small increases in cell entry compared to D614G alone in 293T cells and human airway organoids. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 pmid:33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022 E154K NC_045512.2:g.460G>A YP_009724390.1:p.Glu154Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022,22915,22916,22917,23012,23399,23401,23402,23403,23604 E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 15 Pfizer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~3x (compared to ~11x for B.1.351). [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022,22915,22916,22917,23012,23399,23401,23402,23403,23604 E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abrogates Bamlanivimab neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Significant decrease in combined Etesevimab+Bamlanivimab neutralization except at the highest concentration measured. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022,22915,22916,22917,23012,23399,23401,23402,23403,23604 E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In two of eight cell lines tested (Caco-2 intenstinal and Calu-3 lung), a modest increase in cell entry was observed. This increase was not observed in a Calu-3 cell line with overexpressed ACE2. [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022,22915,22916,22917,23012,23399,23401,23402,23403,23604 E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Approximately 2-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034 R158G,R158G NC_045512.2:g.467_472del,NC_045512.2:g.472A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22033,23012,23604 F157L,E484K,P681R NC_045512.2:g.471C>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against A.23.1-v2 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22033,23604 F157L,P681R NC_045512.2:g.471C>A,NC_045512.2:g.2042C>G YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against A.23.1-v1 reduced 1.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22036 R158S NC_045512.2:g.474A>T YP_009724390.1:p.Arg158Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected three times in passage with mAb COV2-2489. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 pmid:33501445 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*16:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:02. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*07:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:02. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DPB1*04:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:03. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type C*07:02. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22107,22111 Q183H,Q183H NC_045512.2:g.549G>T,NC_045512.2:g.549G>T YP_009724390.1:p.Gln183His,YP_009724390.1:p.Gln183His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 pmid:33176080 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22132 R190S NC_045512.2:g.570G>T YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.69 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604 R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in B.1.640.2 variant was ~1000x folds more significant in 8 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 pmid:35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604 R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1.640.2 variant was ~5.6x folds more significant in 9 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 pmid:35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22188,23399,23401,23402,23403 I210del,D614G,D614G,D614G,D614G NC_045512.2:g.629_631del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection A 42yo Iranian male was reinfected with B.1.36 lineage virus 128 days after infection with genetically distinct B.1.36 virus, with negative PCR tests in between. In the first instance patient presented with cough, headache, severe diarrhea. In the second instance symptoms were more severe: body pain, shortness of breath, headache and anosmia. Anti-SARS-CoV-2 IgG and IgM tests were negative after both episodes. [Non-seroconversion may be associated with elevated risk of re-infection] [I210del is a homoplasy that has appeared in several disparate parts of the global phylogenetic tree, including A and B lineages, primarily in LMICs] Salehi-Vaziri 2021 https://doi.org/10.1016/j.virusres.2021.198421 doi:10.1016/j.virusres.2021.198421 pmid:33836204 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.98 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*13:02. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 pmid:34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:01. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 pmid:34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:02. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 pmid:34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2:g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22224,22227 A222V,A222V NC_045512.2:g.665C>T,NC_045512.2:g.665C>T YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not associated with significant reduction of EC50 (recognition) in any antigenic supersite 'i' monoclonal antibodies. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22224,22227,23399,23401,23402,23403 A222V,A222V,D614G,D614G,D614G,D614G NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3). Both cases were mild. Second case also includes N:p.A220V Brehm 2021 https://doi.org/10.3390/v13040661 doi:10.3390/v13040661 pmid:33921216 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22224,22227,23399,23401,23402,23403 A222V,A222V,D614G,D614G,D614G,D614G NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) humoral response durability 27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3), i.e. with a 9 month interval. Both cases were mild. No significant differences in the neutralizing capacity of the two lineages were observed in 4 sera taken (1 pre-reinfection, three post-reinfection). Neutralizing antibody titres (IC50) before and immediately after re-infection were <300 against both strains, and jumped >7x upon re-infection. Viral titres were also higher in the second case. Second case also includes N:p.A220V Brehm 2021 https://doi.org/10.3390/v13040661 doi:10.3390/v13040661 pmid:33921216 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22293 L244S NC_045512.2:g.731T>C YP_009724390.1:p.Leu244Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22301 S247R NC_045512.2:g.739A>C YP_009724390.1:p.Ser247Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22304 Y248H NC_045512.2:g.742T>C YP_009724390.1:p.Tyr248His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22314 P251L NC_045512.2:g.752C>T YP_009724390.1:p.Pro251Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317 G252D NC_045512.2:g.755G>A YP_009724390.1:p.Gly252Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317,22319,22320 D253G,D253G,D253G NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317,22319,22320 D253G,D253G,D253G NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite 'i', but no effect on other mAbs within that supersite McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22319 D253Y NC_045512.2:g.757G>T YP_009724390.1:p.Asp253Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite 'i', but no effect on other mAbs within that supersite McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22323 S254F NC_045512.2:g.761C>T YP_009724390.1:p.Ser254Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not associated with significant reduction of EC50 (recognition) in any antigenic supersite 'i' monoclonal antibodies. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22323 S254Y NC_045512.2:g.761C>A YP_009724390.1:p.Ser254Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22326 S255F NC_045512.2:g.764C>T YP_009724390.1:p.Ser255Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22328,22329,22331 G257S,G257S,G257S NC_045512.2:g.769G>A,NC_045512.2:g.769G>A,NC_045512.2:g.769G>A YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334 W258R NC_045512.2:g.772T>C YP_009724390.1:p.Trp258Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334 W258R NC_045512.2:g.772T>C YP_009724390.1:p.Trp258Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334,22879,22881,22882,22882,22904,22910,23012 W258R,N440K,N440K,N440K,N440K,N450D,N450D,E484K NC_045512.2:g.772T>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22340 A260T NC_045512.2:g.778G>A YP_009724390.1:p.Ala260Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22344 G261D NC_045512.2:g.782G>A YP_009724390.1:p.Gly261Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Multiple mink but no humans on one farm in Denmark, potential adaptation. Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 pmid:33172935 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22377 P272L NC_045512.2:g.815C>T YP_009724390.1:p.Pro272Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*02:01. Dolton 2021 https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf doi:10.1101/2021.06.21.21259010v2.full.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22377 P272L NC_045512.2:g.815C>T YP_009724390.1:p.Pro272Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*08:01. Dolton 2021 https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf doi:10.1101/2021.06.21.21259010v2.full.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 1.2x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.3 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22583 V341I NC_045512.2:g.1021G>A YP_009724390.1:p.Val341Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22595,22596,22597,22599 R346T,R346T,R346T,R346T NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22595,22596,22597,22599 R346T,R346T,R346T,R346T NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.15 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22595,22596,22597,22599,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22939,22942,22942,22992,23009,23010,23012,23013,23027,23029,23030,23031,23053,23054,23055,22992,22995,23060,23061,23062,23063,23071,23074,23075 R346T,R346T,R346T,R346T,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N460K,N460K,N460K,S477N,E484A,E484A,E484A,E484A,F490S,F490S,F490S,F490S,Q498R,Q498R,Q498R,T478K,T478K,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The hACE2-binding affinity of XBB.1.5 RBD has a dissociation constant KD of 3.4 nM, where S486P is the distinguishing Spike mutation vs parent XBB.1 RBD with a much weaker KD (19 nM), as measured by surface plasmon resonance (SPR) assays. Yue 2023 https://doi.org/10.1101/2023.01.03.522427 doi:10.1101/2023.01.03.522427 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346K,R346K NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 53% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346K,R346K NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation, which has emerged in some Omicron sequences, has a 0.7x reduction in neutralization activity with Sotrovimab in a VSV model on Vero E6 cells. [Omicron sequences with R346K may very well have a non-additive neutralization rather than 2.7x+0.7x = 3.4x] Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346K,R346K NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346I,R346I NC_045512.2:g.1037G>T,NC_045512.2:g.1037G>T YP_009724390.1:p.Arg346Ile,YP_009724390.1:p.Arg346Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Provides ~80% escape from mAb COV2-2130, even though its appearance in culture is formed without selective mAb pressure. Dong 2021 https://doi.org/10.1101/2021.01.27.428529 doi:10.1101/2021.01.27.428529 pmid:33532768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 pmid:33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 2/3 antibody C603. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Positive selection (up to 30% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22622 N354D NC_045512.2:g.1060A>G YP_009724390.1:p.Asn354Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.13 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22624 N354K NC_045512.2:g.1062C>A YP_009724390.1:p.Asn354Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22627,22629 K356T,K356T NC_045512.2:g.1067A>C,NC_045512.2:g.1067A>C YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.14 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22629 K356R NC_045512.2:g.1067A>G YP_009724390.1:p.Lys356Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22632 R357K NC_045512.2:g.1070G>A YP_009724390.1:p.Arg357Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.18 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2:g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2:g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.72 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2:g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as 'stabilizing' since it nicely fitsinside the hydrophobic pocket formed in the RBD domain. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22661 V367I NC_045512.2:g.1099G>A YP_009724390.1:p.Val367Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22679 S373P NC_045512.2:g.1117T>C YP_009724390.1:p.Ser373Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Reduce affinity for mildly cross-reactive CR3022 (2003 pandemic SARS monoclonal antibody cross-reactive to SARS-CoV-2) Long 2020 https://doi.org/10.1128/mBio.02707-20 doi:10.1128/mBio.02707-20 pmid:33127862 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22679,23009,23010,23012,23013 S373P,E484A,E484A,E484A,E484A NC_045512.2:g.1117T>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility On December 7, 2021 the estimate of Omicron effective reproduction rate (Rt) is 3.12 [presumably R0 is higher], compared to 1.12 for the dominant Delta VOC at that time. [shorthand of variant list shraed by all contemporary BA lineage used here] 2021 https://doi.org/10.47326/ocsat.dashboard.2021.1.0 doi:10.47326/ocsat.dashboard.2021.1.0 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22686 S375F NC_045512.2:g.1124C>T YP_009724390.1:p.Ser375Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. Lucaci 2021 https://observablehq.com/@aglucaci/sc2-omicron Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22696 K378N NC_045512.2:g.1134G>T YP_009724390.1:p.Lys378Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for mildly neutralizing COV2-2677 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23402,23403 P384L,D614G,D614G,D614G,D614G NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23402,23403 P384L,D614G,D614G,D614G,D614G NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23402,23403 P384L,D614G,D614G,D614G,D614G NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22745 V395I NC_045512.2:g.1183G>A YP_009724390.1:p.Val395Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22766 I402V NC_045512.2:g.1204A>G YP_009724390.1:p.Ile402Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22783,22784,22785,22786,22786 R408S,R408S,R408S,R408S,R408S NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22783,22784,22785,22786,22786,23009,23010,23012,23013,23060,23061,23062,23063 R408S,R408S,R408S,R408S,R408S,E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a study of 481 vaccinees going from lowest to highest infection rate, 2 doses of CoronaVac and 1 dose of BNT162b2 had the lowest infection rate at 6.3%, then it was 3 doses of BNT162b2 having a infection rate of 16.6%. 2 and 3 doses of CoronaVac had 48.6% and 20.6% infection rate respectively. 2 doses of BNT162b2 has the highest infection rate at 49.2%. Zhou 2022 https://doi.org/10.1101/2022.05.09.491254 doi:10.1101/2022.05.09.491254 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 36.9 fold decrease in KD value for antibody binding of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 1.5 fold decrease in KD value of antibody binding of ACE2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 19 convalescent human sera ~1mo post infection, Two-tailed Wilcoxon matched-pairs signed-rank test shows mild resistance P=0.0361. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs) Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 7.5 fold decrease in KD value for antibody binding of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 1.1 fold drop in IC50 of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.86 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C682, and to a lesser extent C614 and C660 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~6x binding against this isolated mutation. Estesevimab lost ~100x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotyped virus model ablates binding by RBD-directed mAbs CB6 and 910-30 (targeting the inner side of the RBD). Pseudotyped virus model impairs binding by RBD-directed mAbs 4-20 and REGN10933. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 3-fold decrease in affinity compared to wild-type RBD on the cell surface (Kd = 145.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects >20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against IgG1 monoclonal antibody ab1. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The K417N mutation decreased the affinity ~4 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813 K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This combination showed ~3x increase binding to ACE2 vs wild type, about half that of the B.1.1.7 lineage, suggesting that the K417N mutation is slightly detrimental to ACE2 binding, probably as a result of disrupting the salt bridge formed with ACE2 residue D30 Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y. Laffeber 2021 https://doi.org/10.1101/2021.02.22.432357 doi:10.1101/2021.02.22.432357 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021 https://doi.org/10.1101/2021.03.04.433887 doi:10.1101/2021.03.04.433887 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of the B.1.351 RBD variants for ACE2 increased by 3.7 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from B.1.351. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 pmid:33619479 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 ('South African') lineage background Wibmer 2021 https://doi.org/10.1101/2021.01.18.427166 doi:10.1101/2021.01.18.427166 pmid:33501446 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM). Ramanathan 2021 https://doi.org/10.1101/2021.02.22.432359 doi:10.1101/2021.02.22.432359 pmid:33655251 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 pmid:33619479 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load B.1.351 and P.1 samples showed average Ct cycle threshold of 22.2 vs 23 for wildtype (i.e. ~60% higher viral load) comparing 3360 and 22535 samples respectively. Roquebert 2021 https://doi.org/10.1101/2021.03.19.21253971 doi:10.1101/2021.03.19.21253971 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In Moderna vaccinee sera, 2.7x reduction in neutralization, and 6.4 for the full B.1.351 Spike mutation complement, but despite the observed decreases, titers in human vaccinee sera against the B.1.351 variant remained at clinically significant level of ~1/300. Wu 2021 https://doi.org/10.1101/2021.01.25.427948 doi:10.1101/2021.01.25.427948 pmid:33501442 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 1.4-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.351 key variants lentivirus. Compare to 8.8-fold reduction against cultured B.1.351 virus. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 pmid:33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibodies ab8 and IgG1 ab1. Complete loss for the same antibodies was also observed against S1 pseudotyped and full Spike protein trimers with both B.1.351 and P.1 lineage variants, with slight binding signal for P.1 against IgG1 at the highest concentration tested (1uM). Complete loss of neutralization by these two antibodies was also observed. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape 27% of 44 early pandemic exposure convalescent plasma/sera lose all activity against a RBD triple mutant pseudovirus (RBD mutatants of the 501Y.V2 'South African' lineage), while only 23% retained high titres Wibmer 2021 https://doi.org/10.1101/2021.01.18.427166 doi:10.1101/2021.01.18.427166 pmid:33501446 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure. Pearson 2021 https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) with enrollment June 24 and November 9, 2020 from ~2000 HIV-negative 18-64 year olds (1:1 placebo to treatment), incidence of serious adverse events 14 or more days post- 2nd dose was balanced between the vaccine and placebo groups. A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed 3.5x reduction in neutralization (ID50) for B.1.351 RBD pseudotype HIB-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a similar 3.2x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera). Madhi 2021 https://doi.org/10.1056/NEJMoa2102214 doi:10.1056/NEJMoa2102214 pmid:33725432 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abolished neutralization by mAbs CQ026 and CQ038, greatly diminished neutralization by CQ012 and CQ046. Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China). Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Average ~10-fold reduction in neutralization efficacy in convalescent sera of 16 health workers infected in Spring 2020. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 2 (B.1.351) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2. Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility 36,590 variant-specific RT-PCR tests were performed on samples collected between April 12 and May 7, 2021 in France to compare variant spread. Compared to January to March 2021, B.1.351 variant had a significant transmission advantage over B.1.1.7 in some regions (15.1 to 16.1% in Île-de-France and 16.1 to 18.8% in Hauts-de-France). This shift in transmission advantage is consistent with the immune evasion abilities of B.1.351 and the high levels of immunization in these regions. Roquebert 2021 https://doi.org/10.1101/2021.05.12.21257130 doi:10.1101/2021.05.12.21257130 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant of key B.1.351 lineage mutations showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23012,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23041,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness 100% of the 5 8‑month‑old male R3P1-E4 antibody treated mice suvived 14 days after infection while only 60% the control group mice survived 5 days post infection. Li 2022 https://doi.org/10.1186/s13578-022-00794-7 doi:10.1186/s13578-022-00794-7 pmid:35581593 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23041,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trachea viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~750x fold drop in the R3P1-E4 antibody in comparison to the IgG control. Li 2022 https://doi.org/10.1186/s13578-022-00794-7 doi:10.1186/s13578-022-00794-7 pmid:35581593 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23041,23060,23061,23062,23063 K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Lung viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~2266x fold drop in the R3P1-E4 antibody in comparison to the IgG control. Li 2022 https://doi.org/10.1186/s13578-022-00794-7 doi:10.1186/s13578-022-00794-7 pmid:35581593 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (no synergy as level approx. that of N501Y alone). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~5x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied] Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22811,22812,22813,22813,23399,23401,23402,23403 K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.64 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In vitro selection against class 1 antibody C682 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The K417T mutation decreased the affinity ~2 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~16x binding against this isolated mutation. Estesevimab lost ~16x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 1.1 fold decrease in KD value of antibody binding of ACE2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.25 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 2.9 fold decrease in KD value for antibody binding of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 57.1 fold decrease in KD value for antibody binding of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417T NC_045512.2:g.1250A>C YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 2.6 fold increase in IC50 of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,23012,23060,23061,23062,23063 K417T,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from P.1. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,23012,23060,23061,23062,23063 K417T,E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of the P.1 RBD variants for ACE2 increased by 5.3 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,23012,23060,23061,23062,23063,23399,23401,23402,23403 K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The KD for the pseudotyped P.1-ACE2 interaction is 4.8 nM, showing that binding to P.1 is essentially indistinguishable from B.1.351 (4.0 nM), which binds with ~19x greater affinity that wild type. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 pmid:33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2:g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22851 T430I NC_045512.2:g.1289C>T YP_009724390.1:p.Thr430Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22865 A435S NC_045512.2:g.1303G>T YP_009724390.1:p.Ala435Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to neutralizing mAb H014 (on D614G background) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 3 antibody C669 mildly selected for the emergence of the N440K mutation in vitro (in contrast to N440H which caused mild escape in Class 1/2 mAb C653). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The N440K variant produced ten times higher infectious viral titers than a prevalent A2a strain, and over 1000 folds higher titers than a much less prevalent A3i strain prototype in Caco2 cells. Interestingly, A3i strain showed the highest viral RNA levels, but the lowest infectious titers in the culture supernatants, indicating the absence of correlation between the RNA content and the infectivity of the sample. Tandel 2021 https://doi.org/10.1101/2021.04.30.441434 doi:10.1101/2021.04.30.441434 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Positive selection (up to 45% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, eliminated in subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 0.7x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 pmid:33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects N501Y substitution decreased the neutralizing and binding activities of CB6 and increased that of BD-23 Cheng 2021 https://doi.org/10.1186/s12985-021-01554-8 doi:10.1186/s12985-021-01554-8 pmid:33910569 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882 N440K,N440K,N440K,N440K NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22881,22882,22882,23399,23401,23402,23403 N440K,N440K,N440K,N440K,D614G,D614G,D614G,D614G NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection A 47yo Indian male was reinfected with B.1.36 lineage virus in September 2020 after infection with genetically distinct B.1.36 virus in July, with negative PCR tests in between. While the forst episode was asymptomatic, the second included fever, cough, and malaise. The second case additionally contained stopgain ORF3a:E261* Rani 2021 https://doi.org/10.1002/jmv.26997 doi:10.1002/jmv.26997 pmid:33818797 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444R NC_045512.2:g.1331A>G YP_009724390.1:p.Lys444Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Identified in 6/20 replicates of recombinant VSV growth in the presence of mAb COV2-2130. Dong 2021 https://doi.org/10.1101/2021.01.27.428529 doi:10.1101/2021.01.27.428529 pmid:33532768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444R NC_045512.2:g.1331A>G YP_009724390.1:p.Lys444Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 20% of supernatant sequences) under two rounds of COV-NY convalescent plasma passage, eliminated in rounds three and four Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444T NC_045512.2:g.1331A>C YP_009724390.1:p.Lys444Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444T NC_045512.2:g.1331A>C YP_009724390.1:p.Lys444Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444T NC_045512.2:g.1331A>C YP_009724390.1:p.Lys444Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Results in 3.7-fold drop in neutralization potency for COVA2-29, which is a cluster I RBD141 specific antibody. Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 14% of supernatant sequences) after COV-NY convalescent plasma assay Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-01 and moderately resistant to 2H04 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects ~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abolishes binding efficiency vs wild type for mAb REGN10933. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Improvement in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22896 V445A NC_045512.2:g.1334T>C YP_009724390.1:p.Val445Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 41% appearance in 2 passages against Regeneron monoclonal antibody RGN10987 @ 10ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 pmid:32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Decrease in neutralization capability of all 4 convalescent sera tested (1 ablated). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 1 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-02, SARS2-32 and SARS2-35 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2499 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2:g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed a ~4x drop in sensitivity. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 95% appearance in 2 passages against Regeneron monoclonal antibody RGN10934 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 pmid:32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-07 nd moderately resistant to SARS2-16 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 4 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Most effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations), triple replicates. Against a broader panel of 16 convalescent plasma (no replicates), reductions in neutralization are considerably less dramatic in pattern, and sometime neutralization increases. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910,23012,23039,23040,23373,25046 N450D,N450D,E484K,Q493R,Q493R,T604I,P1162S NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1811C>T,NC_045512.2:g.3484C>T YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Thr604Ile,YP_009724390.1:p.Pro1162Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22905 N448S NC_045512.2:g.1343A>G YP_009724390.1:p.Asn448Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22907 Y449N NC_045512.2:g.1345T>A YP_009724390.1:p.Tyr449Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22907 Y449H NC_045512.2:g.1345T>C YP_009724390.1:p.Tyr449His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2:g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912,22916 L452M,L452M NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912,22916 L452M,L452M NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-02 and SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking We observed increased entry by pseudoviruses carrying the L452R mutation compared to D614G alone, with a 6.7 to 22.5-fold increase in 293T cells and a 5.8 to 14.7-fold increase in human airway organoids. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 pmid:33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.32 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~1.7-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Increased stability of RBD expression in yeast, suggesting increased Spike protein stability. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects ~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. L452R conferred about a two-fold reduction in neutralisation by vaccine sera, but was not statistically significant with this sample size. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion L452R derivative virus did not induce IFN-gamma expression even at the highest concentration tested (10 nM) in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456). Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs X593 and P2B-2F6 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. [listed as L454R in Figure, but L452R in text, also text suggests not statistically significant, but error bars say otherwise in Figure 4] Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021 https://doi.org/10.1101/2021.04.14.21255431 doi:10.1101/2021.04.14.21255431 pmid:33907767 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 10 of 14 RBD-specific mAbs that showed at least 10-fold reduced neutralization of B.1.427/B.1.429 variant pseudotype (S13I, W152C, and L452R) were also found to poorly bind to just a L452R RBD mutant, demonstrating a role for this mutation as an escape mechanism for certain RBD-targeting mAbs. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02. Motozono 2021 https://doi.org/10.1016/j.chom.2021.06.006 doi:10.1016/j.chom.2021.06.006 pmid:34171266 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2/3 antibody C628 and class 2 antibody C643 selected for the emergence of the L452R mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.67 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Ablation of neutralization capability of 3 of 4 convalescent sera tested, the other is significantly hindered. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Observed ~2x decrease on average in neutralization efficacy in convalescent sera of 16 health workers. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 3 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~5x binding against this isolated mutation. Cligavimab lost ~4x binding against this isolated mutation. Regdanvimab lost ~4x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917 L452R,L452R,L452R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012 L452R,L452R,L452R,E484Q NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484Q had a ~5x drop in neutralization (vs ~10x for E484K). When E484Q and L452R were combined, the fold change was significant, but similar to that of L452R alone (~2x), suggesting no evidence for an additive effect [perhaps even E484Q effect dilution]. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012 L452R,L452R,L452R,E484K NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant combination shows a ~4-5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, same as L452R alone. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x infectivity advantage to the spike particles [less than L452R or E484Q alone working with the delins]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The combination caused a 3-fold increase in infectivity relative to D614G wild type. [compare to 3.5x for L452R alone] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2.5x. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.617) showed a 1.30x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.18x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Pseudotyped viruses for B.1.617 was 2.3-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. [details on the convalescent patient sera collection are not abundantly clear in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x drop in neutralization (NT50) [working with the delins, less than just L452R but more than just E484Q]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617) showed a 1.85x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.617) showed a 1.22x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23604 L452R,L452R,L452R,E484Q,P681R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load In 9 infected hamsters each for B.1 and B.1.617.1, no significant change in viral load or subgenomic RNA levels were detected. Yadav 2021 https://doi.org/10.1101/2021.05.05.442760 doi:10.1101/2021.05.05.442760 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23604 L452R,L452R,L452R,E484K,P681R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant combination shows a ~3x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, significantly less of a decrease than any B.1.617 lineage variants alone, suggesting a synergistic effect on cell entry while maintaining known immunity esacpe mutants. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23604 L452R,L452R,L452R,E484Q,P681R NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence Gross examination of 3+3 hamster lung specimens showed pronounced congestion and hemorrhages on days 5 and 7 post-infection in the case of the B.1.617.1 as compared with the B.1. The lung lesions with the B.1 variant were minimal to mild whereas with B.1.617.1 they were moderate. For B.1 pneumonic changes were minimal to mild (inflammatory cell infiltration, focal consolidation and mild congestion). The pronounced changes (moderate to severe) with mononuclear infiltration in the alveolar interstitial space, interstitial septal thickening, consolidation and pneumocyte hyperplasia were observed with B.1.617.1 variant consistently. Yadav 2021 https://doi.org/10.1101/2021.05.05.442760 doi:10.1101/2021.05.05.442760 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23012,23604,23399,23401,23402,23403 L452R,L452R,L452R,E484Q,P681R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Normalized for particle number, on ACE2.293T cells showed that the B.1.617 spike protein was >2-fold increase in infectivity relative to D614G wild type. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23060,23061,23062,23063 L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The presence of these B.1.417/B.1.429 defining variants in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021 https://doi.org/10.1101/2021.04.14.21255431 doi:10.1101/2021.04.14.21255431 pmid:33907767 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 583 test-positive were Epsilon. Two dose vaccine efficacy against Epsilon was 97.6 (90.2-99.4%), one dose VE was 76.3 (48.1-89.1%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 7.42x drop in neutralization (NT50) [mostly from 3 of the sera]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The L452R mutation increased the infectivity more than two-fold in these conditions. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this RBD mutation conferred a 2.36x drop in neutralization (NT50). Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2x. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~2x infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22916,22917,23399,23401,23402,23403 L452R,L452R,L452R,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917 L452Q NC_045512.2:g.1355T>A YP_009724390.1:p.Leu452Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917 L452Q NC_045512.2:g.1355T>A YP_009724390.1:p.Leu452Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.27 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917,23027,23029,23030,23031,23399,23401,23402,23403 L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 1.7x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917,23027,23029,23030,23031,23399,23401,23402,23403 L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.048x fold change in IC50 in C.37 Lambda Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917,23027,23029,23030,23031,23399,23401,23402,23403 L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 3.4x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917,23027,23029,23030,23031,23399,23401,23402,23403 L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.038x fold change in IC50 in C.37 Lambda Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.25 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape VSV pseudotyped with Y453F reduced inhibition by most of the 13 potent convalescent serum/plasma samples tested, albeit with variable efficiency (median increase of serum/plasma titer required for 50% neutralization [NT50] = 1.62x, range = 1.02x to 3.43x), indicating that this RBD mutation may compromise SARS-CoV-2 control by preexisting neutralizing antibody responses. Hoffman 2021 https://doi.org/10.1016/j.celrep.2021.109017 doi:10.1016/j.celrep.2021.109017 pmid:33857422 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 10-fold reduction in binding efficiency vs wild type for MAb REGN10933. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Casirivimab lost >50x binding against this mutation. Hoffman 2021 https://doi.org/10.1016/j.celrep.2021.109017 doi:10.1016/j.celrep.2021.109017 pmid:33857422 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02. Motozono 2021 https://doi.org/10.1016/j.chom.2021.06.006 doi:10.1016/j.chom.2021.06.006 pmid:34171266 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 pmid:33172935 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion The induction level of IFN-gamma expression by the Y453F derivative in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456) was significantly lower. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~12x binding against this double mutation. Casirivimab lost ~64x binding against this double mutation. Cligavimab lost ~6x binding against this double mutation. Estesevimab lost ~10x binding against this double mutation. Imdevimab lost ~5x binding against this double mutation. Regdanvimab lost ~8x binding against this double mutation. Sotrovimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed in 4 separate mink farms in Denmark, and Y453F is circulating relatively widely in humans. Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 pmid:33172935 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2:g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~4-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920,21762,21763,21764,21765,21766,21766,21761 Y453F,H69del,H69del,H69del,H69del,H69del,H69del,V70del NC_045512.2:g.1358A>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence The so-called 'delta F' variant combination previously observed in mink spillover events also emerged in a lymphoma patient (non-Hodgkin diffuse B-cell lymphoma IV stage B) with a long-term COVID-19 infection (4 months) where 18 de novo mutation occureed overall. Patient was taking rituximab, the B-cell-depleting agent, and had no detectable neutralizing antibody response. Bazykin 2021 https://virological.org/t/emergence-of-y453f-and-69-70hv-mutations-in-a-lymphoma-patient-with-long-term-covid-19/580 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22924,22925,22926 L455S,L455S,L455S NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.45 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22926,22927,22927,22928,22930,22930 F456L,F456L,F456L,F456L,F456L,F456L NC_045512.2:g.1366T>C,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>A,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>G,NC_045512.2:g.1368T>A YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects This double substitution reduces neutralization by RBD-specific mAbs from different clusters, specifically, the cluster I mAb COVA2-29, cluster III mAb COVA2-07 and cluster VI mAb COVA1-12. For COVA1-12 all neutralization activity is abolished, while COVA2-07 activity is just below the level required to calculate an IC50 value. Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22928 F456V NC_045512.2:g.1366T>G YP_009724390.1:p.Phe456Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22928 F456V NC_045512.2:g.1366T>G YP_009724390.1:p.Phe456Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Moderate in vitro selection against class 1 (Spike 'up' conformation) antibodies C683 and C664. Unclassified antibody C666 selected for the emergence of the F456V mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22936 K458N NC_045512.2:g.1374G>T YP_009724390.1:p.Lys458Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22939,22942,22942 N460K,N460K,N460K NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.09 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460H NC_045512.2:g.1378A>C YP_009724390.1:p.Asn460His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Mild escape mutant emergent for class 1 antibody C613 in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460Y NC_045512.2:g.1378A>T YP_009724390.1:p.Asn460Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460H NC_045512.2:g.1378A>C YP_009724390.1:p.Asn460His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22941 N460I NC_045512.2:g.1379A>T YP_009724390.1:p.Asn460Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22941 N460S NC_045512.2:g.1379A>G YP_009724390.1:p.Asn460Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22964 I468V NC_045512.2:g.1402A>G YP_009724390.1:p.Ile468Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22964 I468V NC_045512.2:g.1402A>G YP_009724390.1:p.Ile468Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22976 I472V NC_045512.2:g.1414A>G YP_009724390.1:p.Ile472Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22976 I472V NC_045512.2:g.1414A>G YP_009724390.1:p.Ile472Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to neutralizing mAb X593 (on D614G background) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~50x binding against this isolated mutation. Estesevimab lost ~8x binding against this isolated mutation. Sotrovimab lost ~30x binding against this isolated mutation. Tixagevimab lost ~15x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some class 1 (Spike 'up' conformation) antibodies tested. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 pmid:33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2:g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C102, C105 and C144 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 pmid:33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 11 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.22 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding, with increasing proportion in subsequent rounds. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility. Singh 2021 https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows some resistence across all antibodies tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 pmid:33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mixed bag of mild positive and negative changes in neutralization capability of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), 10 show low neutralization. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects While S477N itself is highly resistent to a broad range of monoclonal antibodies, combined with S514F high neutralization is restricted to only three antibodies in a broad screen. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-07, SARS2-16 and SARS2-19 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 host variant dependency This mutation's measured interaction affinity with ACE2:p.S19P (0.03% minor allele frequency, found almost exclusively in African/African-Americans in the GnomAD database) was significantly lower than the predicted value, indicating that these mutations were not independent. This is consistent with the fact that the ACE2 residue S19 is adjacent to RBD residue S477 in the contact interface. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-07 and SARS2-16 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2:g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 2.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,22995,23042 T478K,T478K,S494P NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1480T>C YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Combination of RBD mutations appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome complicated by diffuse alveolar hemorrhage, who was receiving anticoagulation therapy, glucocorticoids, cyclophosphamide, and intermittent rituximab and eculizumab. Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 pmid:33176080 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23012 S477N,E484K NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~10x binding against this double mutation. Tixagevimab lost ~16x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23402,23403 S477N,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was neutralized slightly less than D614G in 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23402,23403 S477N,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23402,23403 S477N,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence Compared to the clade 20A strains that predominated during phase 1 between March and May 2020, the Marseille-4 variant (characterized by this mutation plus N:p.M234I;A376T) was associated with a lower frequency of cough, rhinitis, and olfactory and gustatory disorders. By contrast, hypoxemia was more frequent in patients infected with the Marseille-4 variant. Fournier 2021 https://doi.org/10.1016/j.ijid.2021.03.068 doi:10.1016/j.ijid.2021.03.068 pmid:33785459 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23402,23403 S477N,D614G,D614G,D614G,D614G NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 11 cases of re-infection with the 'Marseille-4' variant found within 1028 positive tests, where all of the earlier infections were from different strains. This lineage is also characterized by N:p.M234I;A376T Fournier 2021 https://doi.org/10.1016/j.ijid.2021.03.068 doi:10.1016/j.ijid.2021.03.068 pmid:33785459 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23003 N481Y NC_045512.2:g.1441A>T YP_009724390.1:p.Asn481Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Minor variant in initial round of in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009 V483L NC_045512.2:g.1447G>C YP_009724390.1:p.Val483Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Remarkably, several of the E484 escape mutants were resistant to neutralization at the highest concentration (1:80 initial dilution) of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), all but one show major resistance. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, 1B07, SARS2-32, SARS2-35 and SARS2-07 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in all 4 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape 'E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels' Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 pmid:33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23061,23062,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 152 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 152 S pseudotype was resistant to neutralization. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23061,23062,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This Spike pseudotype for Day 152 virus from a chronically infected patient was completely resistent to REGN10933. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23061,23062,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 152 virus from a chronically infected patient: although mAb C1A-B12 had no activity against this pseudotype, all three affinity optimized versions were active; the antibody containing the most mutations, C1A-B12.3, was the most potent (IC50 <0.5 μg/mL). Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2). Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous. Braeye 2022 https://doi.org/10.1101/2022.05.09.22274623 doi:10.1101/2022.05.09.22274623 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness 3rd exposure to antigen by Delta (B.1.617.2) (n=24) breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a 3rd mRNA vaccine dose in individuals aged 21 –63 years, median age=30 years. Data collected 5.5 months after 2nd vaccination. Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In sera from 17 sero-positive blood donors, and 18 months post-infection (May 2020) sera from 17 health care workers in Sweden, a 40x drop in neutralization by Omicron (B.1.1.529) pseudotyped lentivirus was observed in HEK293T cells using the First WHO International Standard (20/136). Median IC50 reduction was ~6x for the blood donors, and ~4.5x for the health care workers. Sheward 2021 https://drive.google.com/file/d/1CuxmNYj5cpIuxWXhjjVmuDqntxXwlfXQ/view False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23071,23074,23075,22992,23060,23061,23062,23063 E484A,E484A,E484A,E484A,Y505H,Y505H,Y505H,S477N,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1430G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using molecular dynamics simulation, ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations. Zhang 2022 https://doi.org/10.1101/2022.06.05.493249 doi:10.1101/2022.06.05.493249 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape This mutation occurred in 100% of sequenced virions after 12 passages and led to a 4-fold decrease in convalescent plasma neutralization activity Andreano 2020 https://doi.org/10.1101/2020.12.28.424451 doi:10.1101/2020.12.28.424451 pmid:33398278 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 pmid:32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~16x binding against this isolated mutation. Casirivimab lost ~16x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Human sera from 5 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) neutralized this variant 3.4x less relative to reference USA-WA1/2020 strain. 8 convalescent plasma with weak IgG ELISA titre neutralized this variant 2.4x less relative to reference USA-WA1/2020 strain. One plasma failed to neutralize at all. 11 convalescent plasma with moderate IgG ELISA titre neutralized this variant 4.2x less relative to reference USA-WA1/2020 strain. 11 convalescent plasma with high IgG ELISA titre neutralized this variant 2.6x less relative to reference USA-WA1/2020 strain. Jangra 2021 https://doi.org/10.1016/S2666-5247(21 doi:10.1016/S2666-5247(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Analyzing responses to the E484K mutation seen in B.1.351 and P.1 variants, we noted that it did not fall in a region predicted to bind the HLAII alleles tested (table S4). The mutation appeared to have no substantial or differential impact on T cell responses. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 pmid:33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484K conferred a ten-fold reduction in neutralisation by vaccine sera. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in all 4 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Monoclonal antibodies 13G9 and 58G6 maintain fairly high neutralization potency, compared to others interfacing with E484K. Li 2021 https://doi.org/10.1101/2021.04.19.440481 doi:10.1101/2021.04.19.440481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Multiple individuals in two related households were infected with a newly acquired E484K mutation within the B.1.311 lineage. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient's quarantine period. Sabin 2021 https://doi.org/10.1101/2021.10.02.21264415 doi:10.1101/2021.10.02.21264415 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2 antibodies C627, C602, C671, C643, and class 2/3 antibody C603 selected for the emergence of the E484K mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant alone shows a 10x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported moderate increase in affinity compared to wild-type RBD on the cell surface (Kd = 38.5nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape As measured by surface plasmon resonance, RBD with the E484K mutation alone showed a mean 19.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma. Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~20x binding against this isolated mutation. Casirivimab lost ~4x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Of 50 mAbs tested, major loss of neutralization observed for S2N28, S2X615, S2N12, S2X192, S2H7, S2X16, S2X58, S2H70, S2X613, S2D19, S2N22, S2D32, S2H58, S2M11, S2D106, S2X30. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in binding efficiency vs wild type for mAb LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus) Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed 3.3x reduction in IC50 serum dilution concentration for 6 convalescent sera. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 pmid:33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 pmid:33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape due to E484K [given Dec 2020-Apr 2021 time frame of the study, this is assumed to entail both Beta and Gamma lineages]. Chung 2021 https://doi.org/10.1136/bmj.n1943 doi:10.1136/bmj.n1943 pmid:34417165 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers of non-human primate sera after one or two doses of Ad26.COV2.S (Jannsen vaccine) against the variants containing the E484K substitution in the RBD were present but reduced (fold reduction between 3.35–7.78, 95% confidence interval all above twofold difference, one-sample t test). Solfrosi 2021 https://doi.org/10.1084/jem.20202756 doi:10.1084/jem.20202756 pmid:33909009 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 pmid:33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding The only mutation in the B.1.351 lineage that appears to contribute to neutralization reduction (~1.7x across 10 convalescent sera from April 2020 infectees) Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.6 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody VH-Fc ab8 Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-02, 1B07, SARS2-16, SARS2-32, SARS2-35 and 2B04 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects >20% (ELISA significance threshold) drop in antibody binding by this variant against monoclonal antibody VH-Fc ab8. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy E484K pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed a mean 2.8x decrease in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 pmid:33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The neutralizing activity of 15/20 convalescent sera was significantly lower against this pseudotyped virus model Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2:g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 3 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, E484Q shows a notably resistant profile, comparable to or even more resistant than E484K at later time points (i.e. more resistant to immune cell somatic mutation evolution), see Figure 5a,b. Subject C 32 days post-infection showed >>10 fold reduction in neutralization, reducing to ~10-fold by day 104. Subject B 26 days post-infection showed ~10 fold reduction in neutralization, reducing to ~4x at day 113. Notably, Subject B also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 32, and no E484K immune escape at day 104. Subject I 26 days post-infection showed ~10 fold reduction in neutralization, with no reduction in escape at day 102. Notably, Subject I also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 26, and no E484K immune escape at day 102. Greaney 2021 https://doi.org/10.1016/j.chom.2021.02.003 doi:10.1016/j.chom.2021.02.003 pmid:33592168 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Individual variants appearing at <=30% frequency at day 21 in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then appearing all at >95% frequency at day 27. Chen 2021 https://doi.org/10.1101/2021.04.08.21254791 doi:10.1101/2021.04.08.21254791 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484K NC_045512.2:g.1450G>A YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, ELISA tests show 10x reduced efficacy of a majority of isolated antibodies, but only a modest decrease for vaccine plasma overall. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,22597,22599 E484K,R346K,R346K NC_045512.2:g.1450G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E484K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,22810,22811,22812,22813,22813 E484K,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~32x binding against this double mutation. COR-101 lost ~160x binding against this double mutation. Casirivimab lost ~16x binding against this double mutation. Estesevimab lost ~32x binding against this double mutation. Regdanvimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403 E484K,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~13x more infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,22810,22811,22812,22813,22813,23399,23401,23402,23403 E484K,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Approximately as infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of the individual variants). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23053,23054,23055,23060,23061,23062,23063 E484K,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Omicron neutralizing antibodies is 0.722x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.5 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.4 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.5 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Omicron Molnupiravir (MK-4482) had no statistically significant change. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 pmid:35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Omicron neutralizing antibodies is 0.686x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Values taken 28 days after booster dose was given for BBIBP-CorVvaccine to 390 participants with 130 participants in the 0-14d-10m, 0-21d-10m and 0-28d-10m group. The geometric mean titers (GMT) of neutralizing antibody in 0-28d-10m and 0-21d-10m group were significantly higher than 0-14d-10m group at month 3, month 6 and month 10 after the second dose. A sharply decrease by 4.85-fold (GMT: 94.4-20.3), 4.67-fold (GMT: 134.4-28.8) and 4.49-fold (GMT: 145.5-32.4) was observed from day 28 to month 10 after the second dose in 0-14d-10m, 0-21d-10m and 0-28d-10m group, respectively, and they had similar decline kinetics. Yao T 2022 https://doi.org/10.1101/2022.06.22.22276690 doi:10.1101/2022.06.22.22276690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.4 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In the case of VOC B.1.1.7+E484K, the addition of the E484K mutation to N501Y further increased the affinity, to ~15 fold higher than WT RBD (KD ~5 nM), by further increasing the k(on) as measured by surface plasmon resonance. Because the higher k(on) could result in mass transfer limiting binding, we confirmed that the kinetic measurement for this variant was not substantially affected by varying levels of immobilization. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Viral load from lung tissue from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 pmid:35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~17.5x folds more significant in 9 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 pmid:35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~100x folds more significant in 3 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 pmid:35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.025x fold change in IC50 in B.1.1.529 Omicron Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Protection against symptomatic infection caused by Beta/Gamma (assumed by combined presence of N501Y and E484K) was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%). Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)] Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 20 sera from BNT162b2 mRNA vaccine inoculated participants, 6 displayed mild (2x) reductions in neutralization. This variant combination showed the highest reduction, but the magnitude of the differences was small compared to the >4x differences in HA-inhibition titers that have been used to signal potential need for a strain change in influenza vaccines. Xie 2021 https://doi.org/10.1038/s41591-021-01270-4 doi:10.1038/s41591-021-01270-4 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.0015x fold change in IC50 in B.1.1.529 Omicron Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063 E484K,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Viral load from oral swabs from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 pmid:35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation ~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~6x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied] Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~12x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of 501 and 484). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23060,23061,23062,23063,23399,23401,23402,23403 E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~11x, Vero ~10x, and Calu-3 ~11x. Compare to wild type at ~5x across cell types. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.618 was 2.7-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 3-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Pseudotyped viruses for B.1.618 was 2.5-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. [details on the convalescent patient sera collection are not abundantly clear in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The estimated vaccine effectiveness against R.1 strain SARS-CoV-2 infection among residents in a Kentucky skilled nursing facility was 66.2% (95% CI = 40.5%–80.8%) and among health care workers was 75.9% (95% CI = 32.5%–91.4%) in the cohort of only those 14d+ post-vaccination Pfizer booster dose. VE against symptomatic COVID-19 was 86.5% (95% CI = 65.6%–94.7%) among residents and 87.1% (95% CI = 46.4%–96.9%) among HCP. VE against hospitalization was 94.4% (95% CI = 73.9%–98.8%) among residents; no HCP were hospitalized. Three residents died, two of whom were unvaccinated (VE = 94.4%; 95% CI = 44.6%–99.4%). Cavanaugh 2021 https://doi.org/10.15585/mmwr.mm7017e2 doi:10.15585/mmwr.mm7017e2 pmid:33914720 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, RBD-specific mutation E484Q did not significantly confer infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484K,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 1.34x drop in neutralization (NT50) [mostly from a single serum]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403 E484Q,D614G,D614G,D614G,D614G NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~4x infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403,25088 E484K,D614G,D614G,D614G,D614G,V1176F NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the P.1 & P.2 lineages of SARS-CoV-2 in Brazil. The Brazilian arm of the Phase 3 double blind study showed severe/critical disease VE of 81.9% (95% CI: 17.0-98.1), and moderate to severe/critical disease VE of 66.2% (95% CI: 51.0-77.1). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 69.3% of mostly severe infections sequenced as of this report, 69.4% were of P.2 lineage [defining lineage SNPs reported here]. 2021 https://www.fda.gov/media/146217/download False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403,25088 E484K,D614G,D614G,D614G,D614G,V1176F NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped P.2 virus has reduced neutralization activity vs wild type: 5.8x (30 sera Pfizer median 9 days post 2nd dose) and 2.9x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23402,23403,25088 E484K,D614G,D614G,D614G,D614G,V1176F NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs] Sapkal 2021 https://doi.org/10.1101/2021.04.30.441559 doi:10.1101/2021.04.30.441559 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23013 E484V NC_045512.2:g.1451A>T YP_009724390.1:p.Glu484Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23013 E484V NC_045512.2:g.1451A>T YP_009724390.1:p.Glu484Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2:g.1456T>C YP_009724390.1:p.Phe486Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed in 4 separate mink farms in Denmark, but not humans, potential adaptation (diff set of farms than N501T). Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 pmid:33172935 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2:g.1456T>C YP_009724390.1:p.Phe486Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486I NC_045512.2:g.1456T>A YP_009724390.1:p.Phe486Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486I NC_045512.2:g.1456T>A YP_009724390.1:p.Phe486Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 pmid:33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutation causes a greater than 100x fold change in IC50 of Ensovibep. Rothenberger 2021 https://doi.org/10.1101/2021.02.03.429164v4 doi:10.1101/2021.02.03.429164v4 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2:g.1456T>C YP_009724390.1:p.Phe486Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutation causes a greater than 100x fold change in IC50 of Ensovibep. Rothenberger 2021 https://doi.org/10.1101/2021.02.03.429164v4 doi:10.1101/2021.02.03.429164v4 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2:g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 pmid:32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 5 antibodies. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects >60% drop in antibody binding (ELISA) by this variant against monoclonal antibody VH-Fc ab8. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed striking resistance with only 38% neutralization at the highest concentration tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 1 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.13 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape IC50 relative to wildtype drops ~8x in neutralization efficiency between 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-07, SARS2-19, 1B07, SARS2-16 and 2B04 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019 F486S,F486S NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Modest decrease in in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23023 N487K NC_045512.2:g.1461T>G YP_009724390.1:p.Asn487Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, high ACE2 binding affinity loss Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.11 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 pmid:33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Based on structural modelling, this change detected on day 128 sequencing in a chronically infected patient would alter an extensive network of polar interactions with antibody residue R94VH, a germline antibody residue that is conserved in all of the potent VH3-53/3-66-derived antibodies isolated from a convalescent donor 5 weeks after infection. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2:g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody ab8 Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-32. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (3 ablations). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2/3 mAb C603 modestly selected for the emergence of this mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 3 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23030,23031 F490S,F490S,F490S,F490S NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23060,23061,23062,23063 Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This Spike pseudotype for Day 146 virus from a chronically infected patient was completely resistent to REGN10933. The variant had a 4-fold decrease in REGN10987 neutralization sensitivity (2nd component of the Regeneron mAb cocktail). Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23060,23061,23062,23063 Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 146 virus from a chronically infected patient: resistant to neutralization by mAb C1A-B12, and was still resistant to the affinity enhanced antibodies derived from it (i.e. no affinity maturation effect on neutralization). Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23060,23061,23062,23063 Y489H,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 146 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 146 S pseudotype was resistant to neutralization. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) resistant to 3 individual sera at >4x Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Positive selection (up to 23% of supernatant sequences) after C121 monoclonal antibody assay Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs X593, 261-262, H4, and P2B-2F6 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490V NC_045512.2:g.1468T>G YP_009724390.1:p.Phe490Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2:g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody ab8 Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2:g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Dominant (70%) in day 21 of prolonged infection in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then nearly disappearing (<5%) by day 27. Chen 2021 https://doi.org/10.1101/2021.04.08.21254791 doi:10.1101/2021.04.08.21254791 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 pmid:33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2 mAb C627 modestly selected for the emergence of this mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 pmid:33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in binding efficiency vs wild type for mAbs CB6/LY-CoV16 and LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23040 Q493R,Q493R NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 2 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, S484P shows a slightly resistant profile across both timepoints (i.e. resistant to immune cell somatic mutation evolution) Greaney 2021 https://doi.org/10.1016/j.chom.2021.02.003 doi:10.1016/j.chom.2021.02.003 pmid:33592168 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using molecular dynamic simulation, the mildly (~1kcal/mol) enhanced binding energy of this variant is primarily contributed by Tyr505 (−4.98 kcal/mol) which is now involved in a strong hydrogen bonding network with Arg393. Another important energetic contribution comes from the altered orientation of Tyr41 which is now involved with two hydrogen-bonding interactions with Asp355 and Thr500. 2021 https://doi.org/10.1016/j.bbrc.2021.01.035 doi:10.1016/j.bbrc.2021.01.035 pmid:33602511 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-01 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Minor variant selected in late rounds of an in vitro evolution experiment for ACE2 binding. Shown to increase the thermostability but decrease the association rate constant of the RBD to ACE2 Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2:g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Regdanvimab lost ~32x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23048 G496S NC_045512.2:g.1486G>A YP_009724390.1:p.Gly496Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23053,23054,23055,23060,23061,23062,23063 Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. The extent of affinity increase with Q498R and N501Y is not exactly quantified, as E484K always emerged with this duo during in vitro evolution. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Utilizing shark derived vnarbodies, S375F mutation on Omicron RBD disrupts the structure of β-strand, which inhibits binding with 20G6. 20G6 binds to a hidden epitope on RBD which is highly conserved in sarbecoviruses. Feng 2022 https://doi.org/10.1002/smtd.202200387 doi:10.1002/smtd.202200387 pmid:35583124 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C663, and to a lesser extent C613. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy Variant within the six key residues in the receptor binding domain (RBD). Independently reported in UK, Australia (same origin as UK), and South Africa (independent origin). Flores-Alanis 2021 https://doi.org/10.3390/pathogens10020184 doi:10.3390/pathogens10020184 pmid:33572190 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 pmid:33176080 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a modest decrease in neutralization by vaccine plasma was observed. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In 30 samples collected 111 to 260 days post onset of symptoms, the covalescent plasma can neutralize both the reference USA-WA1/2020 strain and the mouse adapted strain that contains the N501Y spike mutation with similar efficiency. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 pmid:33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape by lineage Alpha [defined here as N501Y positive, but E484K negative]. Chung 2021 https://doi.org/10.1136/bmj.n1943 doi:10.1136/bmj.n1943 pmid:34417165 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Human sera from 6 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) can neutralize both the reference USA-WA1/2020 strain and the mouse adapted SARS-CoV-2 strain that contains the N501Y spike mutation with similar efficiency. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 pmid:33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 pmid:33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.69 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x) Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Lowered the neutralization potency of mAb COVA1-12 to the limit of the assay. Decrease in potency was observed against the N501Y pseudotype for the cluster IX mAb COVA2-17. Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Vaccinated, but not post-infection sera, show decreased average T cell response to an N501Y peptide. When we primed transgenic mice expressing human HLA-DRB1*0401 with the Wuhan Hu-1 peptide pool, T cell responses to the B.1.1.7 variant peptide pool were significantly reduced (p = 0.0286). Furthermore, the T cell response to the spike N501Y mutation common to all three of the current VOC was ablated. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 pmid:33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~8x binding against this isolated mutation. Regdanvimab lost ~6x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.2x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 and day 14 post-2nd dose) against a recombinant single variant virus (modified replicating WA-1 cDNA clone) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 pmid:33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021 https://doi.org/10.1101/2021.04.14.21255431 doi:10.1101/2021.04.14.21255431 pmid:33907767 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation alone accounts for most of the increased infectivity of the Alpha variant, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters, and Vero E6 (NHP) and Calu-3 (human) cell lines. Liu 2021 https://doi.org/10.1101/2021.03.08.434499 doi:10.1101/2021.03.08.434499 pmid:33758836 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity. Zhu 2021 https://doi.org/10.1101/2021.01.11.426269 doi:10.1101/2021.01.11.426269 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Contrary to other reports on N501Y containing lineages (i.e. with additional mutations), N501Y alone may have an even greater affinity for a human monoclonal antibody specific for wild type. These results suggest that the individual N501Y mutation does not contribute to altered viral properties by itself, but may contribute to a collective conformational shift produced by multiple mutations. Klegerman 2021 https://doi.org/10.1101/2021.04.26.441517 doi:10.1101/2021.04.26.441517 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape As measured by surface plasmon resonance, RBD with the N501Y mutation alone showed a mean 2.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma. Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape 0.7x reduction in neutralization by key variant in several variants of concern in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~4-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In silico methods (PyMOL and PDBePISA) involving mutagenesis (N501Y mutation) and interface analysis focusing on the Spike RDB-ACE2 interaction showed that the SARS-CoV-2 N501Y mutant (lineage B.1.1.7) establishes a more significant number of interactions relating to the mutant residue Y501 (Spike RDB) with residues Y41 and K353 (ACE2). This finding shows that the increased infectivity of SARS-CoV-2 lineage B.1.1.7 is associated with the interaction force between the Spike RBD Y501 mutant residue with the ACE2 receptor, which in this strain is increased. 2021 https://doi.org/10.1101/2020.12.29.424708 doi:10.1101/2020.12.29.424708 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Of 50 mAbs tested, major loss of neutralization observed for S2X128, S2D8, S2X192, S2D19, S2H14, S2H19. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021 https://doi.org/10.1101/2021.02.02.428884 doi:10.1101/2021.02.02.428884 pmid:33564771 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM). Ramanathan 2021 https://doi.org/10.1101/2021.02.22.432359 doi:10.1101/2021.02.22.432359 pmid:33655251 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The most frequent RBM mutation N501Y (165,519 instances) makes defective the atypical N-glycosylation sequon NGV 501-503, becoming a key RBM position for the interaction with hACE2-binding hotspot 353. Gamez 2021 https://doi.org/10.1101/2021.04.09.439154 doi:10.1101/2021.04.09.439154 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slightly increased infection rate amongst the cells. [in what is essentially a replicate experiment in the same paper, because each B.1.351 lineage variant was independetly evaluated and N501 is in both lineages, a significant decrease was observed, therefore the error bars described in this paper should be interpreted carefully] Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063 N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The N501Y mutation had the biggest effect on ACE2 affinity of any VOC mutation tested, increasing the affinity ~10 fold to KD ~7 nM, by increasing the k(on) ~1.8 fold and decreasing the k(off) by ~ 7 fold as measured by surface plasmon resonance. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,22810,22811,22812,22813,22813 N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~20x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~6x binding against this double mutation. M396 lost ~10x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,22810,22811,22812,22813,22813,23012 N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In post-vaccination sera from individuals who received one (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) of the BNT162b2 Pfizer vaccine, an average 6.8x reduction in neutralization efficacy of this B.1.351 key variants pseudotype lentivirus vs D614G was observed. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,22810,22811,22812,22813,22813,23012 N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape ~7x reduction in neutralization by key B.1.351 lineage RBD variant combination in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Two of the cohort showed no neutralization against this variant. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23012 N501Y,N501Y,N501Y,N501Y,E484K NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~64x binding against this double mutation. COR-101 lost ~50x binding against this double mutation. Casirivimab lost ~250x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~32x binding against this double mutation. Tixagevimab lost ~10x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23271 N501Y,N501Y,N501Y,N501Y,A570D NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Partial sequencing of S gene reveals two cases of probable early 2021 B.1.1.7 lineage reinfection from non-B.1.1.7 original cases in Lombardy, with 45 to 90 days between infections (less than the typical 90 day guideline for this call). Patients were 56 and 58yo, immunocompenent, with one a former smoker with obesity and dyslipidemia. One case required intubation during first infection, but presented with mild symptoms upon reinfection. The other case convalesced at home during the first episode, but required CPAP support in the subacute clinical unit upon reinfection. Novazzi 2021 https://doi.org/10.1002/jmv.27066 doi:10.1002/jmv.27066 pmid:33969504 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking 9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~13x, Vero ~10x, and Calu-3 ~10x. Compare to wild type at ~5x across cell types. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~9x, Vero ~8x, and Calu-3 ~8x. Compare to wild type at ~5x across cell types. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed no change in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation ~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Lentiviral pseudotyped with the key mutations from COH.20G/677H ('Ohio') lineage was neutralized similarly to D614G in 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23399,23401,23402,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells for ACE2 affinity changes vs D614G alone, showing a ~70% drop in IC50 (i.e. increased affinity). Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23063,23521,23522,23524,23525 N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 pmid:33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23071,23074,23075 Y505H,Y505H,Y505H NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed first in a single tiger (cohort of 5), potential adaptation. McAloose 2020 https://doi.org/10.1128/mBio.02220-20 doi:10.1128/mBio.02220-20 pmid:33051368 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23071,23074,23075 Y505H,Y505H,Y505H NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23102 S514T NC_045512.2:g.1540T>A YP_009724390.1:p.Ser514Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23108 E516Q NC_045512.2:g.1546G>C YP_009724390.1:p.Glu516Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23115 L518Q NC_045512.2:g.1553T>A YP_009724390.1:p.Leu518Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23120 A520S NC_045512.2:g.1558G>T YP_009724390.1:p.Ala520Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness CR3022 (SARS-targeting mAb) cross-reactivity lost ~4x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23148 K529T NC_045512.2:g.1586A>C YP_009724390.1:p.Lys529Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.15 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing statistically significant increased infection rate amongst the cells. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant raises PIWAS epitope score from 3.6% to 6.2% (improved immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2:g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated that there is very little free energy change (ddG. -0.02 kcal/mol) for this variant (i.e. approx. same stability as wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23373 T604I NC_045512.2:g.1811C>T YP_009724390.1:p.Thr604Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped D614G virus has reduced neutralization activity vs wild type: 1.2x (37 sera Pfizer median 9 days post 2nd dose, 37 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.53x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a lentivirus virus pseudotyped with D614G Spike, sera from vaccinated individuals who received the second dose (9–11 days post-second dose of Pfizer) exhibited a robust neutralizing potential, with a mean NT50 value of 99,000. This was an average of a 2-fold increase, relative to sera drawn from the individuals who received one dose of vaccination—mean NT50 dilution of 51,300. Importantly, a 6-fold increase in mean NT50 dilution was obtained when sera from the first vaccination dose was compared to convalescent sera from cohort with severe disease (NT50 51,000 vs 8,700) 21 to 63 days post-onset. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 1.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 2.5 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure CryoEM shows increased proportion of 'one-up' trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2. Yurkovetskiy 2020 https://doi.org/10.1016/j.cell.2020.09.032 doi:10.1016/j.cell.2020.09.032 pmid:32991842 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Negative stain EM shows increased proportion of 'one-up' trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2. Weissman 2020 https://doi.org/10.1101/2020.07.22.20159905 doi:10.1101/2020.07.22.20159905 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.97x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD mutation conferred a 4.85x drop in neutralization (NT50). Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 pmid:33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 conferred a nearly two-fold infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In four cell lines (including 293T-hACE2 cells), this mutation combination increases infectivity vs D614G alone Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 pmid:33243994 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 pmid:33243994 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.05x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.45x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.35x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to wild type, D614G showed increased infectivity (ie. cold stability) after storage at -20°C for up to 30 days. Huang 2021 https://doi.org/10.1128/msphere.00104-21 doi:10.1128/msphere.00104-21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation (a.k.a. 'Doug') outside the receptor binding domain, while highly favorable to improved human-human transmission, decreases transduction in naked mole-rat (Heterocephalus glaber) fibroblast and Japanese pipistrelle bat (Pipistrellus abramus) cell cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking The increased transduction with Spike D614G ranged from 1.3- to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2 and from 1.5- to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction. Daniloski 2021 https://doi.org/10.7554/eLife.65365 doi:10.7554/eLife.65365 pmid:33570490 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Studying 94 COVID-19 extended infection cases with genomics April 1 to October 17, 2020, one case developed 23 mutations in a 19 day period, including this combination in Spike. Landis 2021 https://doi.org/10.1101/2021.05.08.21256775 doi:10.1101/2021.05.08.21256775 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission. Plante 2020 https://doi.org/10.1038/s41586-020-2895-3 doi:10.1038/s41586-020-2895-3 pmid:33106671 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses. Ozono 2020 https://doi.org/10.1038/s41467-021-21118-2 doi:10.1038/s41467-021-21118-2 pmid:33558493 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a slight decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403 D614G,D614G,D614G,D614G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.43x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575 D614G,D614G,D614G,D614G,L5F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.1x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575 D614G,D614G,D614G,D614G,L5F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575 D614G,D614G,D614G,D614G,L5F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.23x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664 D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.526) showed a 1.78x increase in binding (KD) relative to D614G, even though each variant independently decreases binding. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664 D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.526) showed a 1.34x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664 D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.526) showed a 1.02x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600 D614G,D614G,D614G,D614G,S13I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600 D614G,D614G,D614G,D614G,S13I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600 D614G,D614G,D614G,D614G,S13I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.42x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600,22018,22915,22916,22917 D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. [Stark contrast to 2.15x increase in binding by convalescent plasma 8 months post infection, presumably via memory B cell affinity maturation against L452R effects] 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600,22018,22915,22916,22917 D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.429 aka Epsilon) showed a 2.82x increase in binding (KD) relative to D614G, indicating a strong marginal effect for L452R. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21600,22018,22915,22916,22917 D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, indicating ablated marginal effect from L452R. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614 D614G,D614G,D614G,D614G,L18F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.66x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Compare to decreased binding in full Spike variant complements for major lineages containing this variant subset: 0.96x (B.1.351 aka Beta), 0.77x (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614 D614G,D614G,D614G,D614G,L18F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.30x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.28x increase (B.1.351 aka Beta), and 1.14x decrease (P.1 aka Gamma). 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.17x increase (B.1.351 aka Beta), and 1.47x decrease (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614 D614G,D614G,D614G,D614G,L18F NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.07x decrease in binding (KD) relative to D614G. Compare to increased binding in full Spike variant complements for major lineages containing this variant subset: 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing P.1 aka Gamma) showed a 4.24x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing P.1 aka Gamma) showed a 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642 D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing P.1 aka Gamma) showed a 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664 D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing B.1.351 aka Beta) showed a 1.28x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. It shows a 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664 D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.351 aka Beta) showed a 3.56x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664 D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing B.1.351 aka Beta) showed a 1.04x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, in contrast to the largely positive binding values for each individual mutation that comprises the set. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21621 D614G,D614G,D614G,D614G,T20N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.39x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21621 D614G,D614G,D614G,D614G,T20N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21621 D614G,D614G,D614G,D614G,T20N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.96x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21638 D614G,D614G,D614G,D614G,P26S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.23x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21638 D614G,D614G,D614G,D614G,P26S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.58x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21638 D614G,D614G,D614G,D614G,P26S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.33x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.51x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing B.1.1.7 aka Alpha) showed no change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.28x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.1.7 aka Alpha) had 5.43x increased binding relative to D614G alone. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914 D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing B.1.1.7 aka Alpha) showed a 1.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21801 D614G,D614G,D614G,D614G,D80A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination showed no change relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21801 D614G,D614G,D614G,D614G,D80A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.64x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.35x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21801 D614G,D614G,D614G,D614G,D80A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21846 D614G,D614G,D614G,D614G,T95I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21846 D614G,D614G,D614G,D614G,T95I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21846 D614G,D614G,D614G,D614G,T95I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21974 D614G,D614G,D614G,D614G,D138Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21974 D614G,D614G,D614G,D614G,D138Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,21974 D614G,D614G,D614G,D614G,D138Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.32x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22018 D614G,D614G,D614G,D614G,W152C NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.03x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22018 D614G,D614G,D614G,D614G,W152C NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.15x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22018 D614G,D614G,D614G,D614G,W152C NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22132 D614G,D614G,D614G,D614G,R190S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.59x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22132 D614G,D614G,D614G,D614G,R190S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22132 D614G,D614G,D614G,D614G,R190S NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.82x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22206 D614G,D614G,D614G,D614G,D215G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.79x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22206 D614G,D614G,D614G,D614G,D215G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.19x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22206 D614G,D614G,D614G,D614G,D215G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D253G,D253G,D253G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.08x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D253G,D253G,D253G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D253G,D253G,D253G NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22810,22811,22812,22813,22813 D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.76x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.75x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22810,22811,22812,22813,22813 D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22810,22811,22812,22813,22813 D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22812 D614G,D614G,D614G,D614G,K417T NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22812 D614G,D614G,D614G,D614G,K417T NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.28x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22812 D614G,D614G,D614G,D614G,K417T NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.66x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.05x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.16x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,22915,22916,22917 D614G,D614G,D614G,D614G,L452R,L452R,L452R NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 4.2x-fold lower (95% CI: 0.15x-0.20x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 6.2-fold lower (95% CI: 11.8x-14.3x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 28.7x-fold lower (95% CI: 0.03x-0.05) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness 4th antigenic exposure with Omicron (B.1.1.529 [BA.1])(n=29) infection increased variant specific plasma antibody and memory B cell responses as well as overall increased strain specific memory in individuals aged 22 –79 years, median age=33.5 years. Data collected 2.4 months after 3rd vaccination. Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 3.4-fold lower (95% CI: 3.2x-3.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy paired testing of vaccine sera against ancestral virus compared to Omicron BA.1 shows that 3-dose vaccine regimen provides over 50x fold increase in protection against Omicron(B.1.1.529 [BA.1]) compared to a 2-dose regimen. Hao 2022 https://doi.org/10.1101/2022.08.12.22278720 doi:10.1101/2022.08.12.22278720 pmid:36032965 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 3.9x-fold lower (95% CI: 0.14x-0.17x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 4.5-fold lower (95% CI: 4.3x-4.7x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 78fM for binding to the Omicron BA.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 4.2-fold lower (95% CI: 5.8x-6.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075 D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 3.9x-fold lower (95% CI: 0.14x-0.18x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23012 D614G,D614G,D614G,D614G,E484K NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.42x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23012 D614G,D614G,D614G,D614G,E484K NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23012 D614G,D614G,D614G,D614G,E484K NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This variant appears twice in the experiments, with slightly different affinities (both ~1.2x decrease in binding relative to D614G) using flow cytometry and ACE2 ectodomains-Fc portion IgG complex. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23060,23061,23062,23063 D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23060,23061,23062,23063 D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23060,23061,23062,23063 D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.52x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis). Compare to full Spike variant complements for major lineages containing this variant subset: 5.43x (B.1.1.7 aka Alpha), 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23271 D614G,D614G,D614G,D614G,A570D NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23271 D614G,D614G,D614G,D614G,A570D NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.18x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23271 D614G,D614G,D614G,D614G,A570D NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23521,23522,23524,23525 D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.48x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23521,23522,23524,23525 D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23521,23522,23524,23525 D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.21x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23604 D614G,D614G,D614G,D614G,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23604 D614G,D614G,D614G,D614G,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant change in virus neutralzation by 18 Pfizer two dose vaccinee sera compared to B.1.1.7. [results without including the used mutation A27S likely generalizable, as this is not a lineage defining mutation] Zuckerman 2021 https://doi.org/10.1101/2021.03.25.21253908 doi:10.1101/2021.03.25.21253908 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23604 D614G,D614G,D614G,D614G,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23604 D614G,D614G,D614G,D614G,P681H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.26x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23664 D614G,D614G,D614G,D614G,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23664 D614G,D614G,D614G,D614G,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23664 D614G,D614G,D614G,D614G,A701V NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed essentially no change in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23709 D614G,D614G,D614G,D614G,T716I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23709 D614G,D614G,D614G,D614G,T716I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.58x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,23709 D614G,D614G,D614G,D614G,T716I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.12x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24506 D614G,D614G,D614G,D614G,S982A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24506 D614G,D614G,D614G,D614G,S982A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24506 D614G,D614G,D614G,D614G,S982A NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.3x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24642 D614G,D614G,D614G,D614G,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.56x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24642 D614G,D614G,D614G,D614G,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.69x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24642 D614G,D614G,D614G,D614G,T1027I NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.22x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24914 D614G,D614G,D614G,D614G,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24914 D614G,D614G,D614G,D614G,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23402,23403,24914 D614G,D614G,D614G,D614G,D1118H NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.96x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23429 A623T NC_045512.2:g.1867G>A YP_009724390.1:p.Ala623Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23522,23524,23525 H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain increases the virus transduction rate in tree shrew (Tupaia belangeri), (as it does in humans) according to pseudotyped VSV experiments. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23522,23524,23525 H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Six minks were intranasally infected with WA1 isolate, all developed this mutation during infection. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23522,23524,23525 H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.87 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23522,23524,23525 H655Y,H655Y,H655Y,H655Y NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23587,23587 Q675H,Q675H NC_045512.2:g.2025G>C,NC_045512.2:g.2025G>T YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly enhanced the ability of the pseudotyped VSV to infect fat-tailed gerbil (Pachyuromys duprasi) kidney cell cultures, with a transduction rate of 13.4%, close to the 15.7% in epithelial-like human Huh-7 cells while starting from a significantly lower wildtype (Wuhan-Hu-1 Spike VSVdeltaG psuedotype) rate. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 0.9x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681R NC_045512.2:g.2042C>G YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. [PG: Inferred by conservative AA substitution of described P681H] Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681R NC_045512.2:g.2042C>G YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). [Inference from similar positively charged substitution P681H actually described in the work] 2021 https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing NO statistically significant infection rate change amongst the cells, suggesting that furin cleavage typically used for cell entry is not affected by this change one amino acid upstream of the RXXR recognition pattern. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). 2021 https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In the absence of N501Y, this Alpha lineage change in the furin clevage site did NOT show significant increase in infectivity relative to wild type, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters. Liu 2021 https://doi.org/10.1101/2021.03.08.434499 doi:10.1101/2021.03.08.434499 pmid:33758836 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic. Johnson 2020 https://doi.org/10.1101/2020.08.26.268854 doi:10.1101/2020.08.26.268854 pmid:32869021 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604 P681H NC_045512.2:g.2042C>A YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking While the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC). Lubinski 2021 https://doi.org/10.1101/2021.04.06.438731 doi:10.1101/2021.04.06.438731 pmid:33851153 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23399,23401,23402,23403 P681R,D614G,D614G,D614G,D614G NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Quantification of the band intensities showed that the P681R mutation, which lies near the proteolytic processing site, caused a small increase in proteolytic processing as measured by a 2-fold decrease in the ratio of S/S2. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23664 A701V NC_045512.2:g.2102C>T YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23664 A701V NC_045512.2:g.2102C>T YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.33 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not in a major wildtype epitope, mutant increases PIWAS epitope score from 0.69% to 2.3% Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed first in a single tiger (cohort of 5), potential adaptation. McAloose 2020 https://doi.org/10.1128/mBio.02220-20 doi:10.1128/mBio.02220-20 pmid:33051368 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain showed a decreased capacity to transduce PK-15 (pig kidney, Sus scrofa) and PaKi (black flying fox kidney, Pteropus alecto) cell line cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2:g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. T716I was expressed at significantly lower level, accounting for the decreased infectivity of this spike protein. This property may be specific to spike protein biosynthesis in 293T cells and is not likely to reflect the situation in vivo given the reported increase in infectivity of the B.1.1.7 virus. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23897 Q779K NC_045512.2:g.2335C>A YP_009724390.1:p.Gln779Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 20% appearance in 2 passages against Regeneron monoclonal antibody RGN10989 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 pmid:32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23948 D796H NC_045512.2:g.2386G>C YP_009724390.1:p.Asp796His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Fatal COVID-19 complications in immunocomprimised patient after immune escape from convalescent plasma Kemp 2020 https://doi.org/10.1101/2020.12.05.20241927 doi:10.1101/2020.12.05.20241927 pmid:33398302 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24000 S813I NC_045512.2:g.2438G>T YP_009724390.1:p.Ser813Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2:g.2492C>T YP_009724390.1:p.Ala831Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2:g.2492C>T YP_009724390.1:p.Ala831Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to neutralizing mAb B38 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2:g.2492C>T YP_009724390.1:p.Ala831Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 pmid:33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24077 D839Y NC_045512.2:g.2515G>T YP_009724390.1:p.Asp839Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry. Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 pmid:33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24077 D839N NC_045512.2:g.2515G>A YP_009724390.1:p.Asp839Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry. Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 pmid:33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24130 N856K NC_045512.2:g.2568C>A YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. Lucaci 2021 https://observablehq.com/@aglucaci/sc2-omicron Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24170 I870V NC_045512.2:g.2608A>G YP_009724390.1:p.Ile870Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Appeared at same time as T478K,S494P but listed separately due to distance and different domains affected in the Spike (i.e. putatively an independent mutation from a functional standpoint since the former are from S1, the latter from S2). Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 pmid:33176080 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24377,24378 S939F,S939F NC_045512.2:g.2816C>T,NC_045512.2:g.2816C>T YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (70%) increase in infection rate amongst the cells, hence this individual variant is likely to significantly contribute to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The neutralizing activity of 6/20 convalescent sera was significantly lower against this single variant pseudotyped virus model, showing similar patterns to the pseudotyped virus model of B.1.1.7. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2:g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24642 T1027I NC_045512.2:g.3080C>T YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 1.51 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 pmid:33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Mutation is predicted to lose the T cell epitope for people carrying DRB1*0301 and DRB1*0401, but not for example in those who are DRB1*0701 or DRB1*1501 who would be predicted to show an enhanced response. This is also observed in a study of 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 pmid:33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2:g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25046 P1162S NC_045512.2:g.3484C>T YP_009724390.1:p.Pro1162Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25249,25249,25249 M1229I,M1229I,M1229I NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25350 P1263L NC_045512.2:g.3788C>T YP_009724390.1:p.Pro1263Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant in the cytoplasmic tail, shown in vitro to increase Spike subunit fusion required for cell entry Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 pmid:33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25855 D155Y NC_045512.2:g.463G>T YP_009724391.1:p.Asp155Tyr open reading frame 3a gene (SARS-CoV-2) orf3a gene (SARS-CoV-2) open reading frame 3a protein (SARS-CoV-2) Orf3a protein (SARS-CoV-2) caveolin binding In silico, this mutation is the only one weakening ORF3a's binding affinity for caveolin-1 (essential for entry and endomembrane trafficking of SARS-CoV-2). This mutation is a widespread homoplasy in 20A and 20B lineages. Gupta 2021 https://doi.org/10.1101/2021.03.26.437194 doi:10.1101/2021.03.26.437194 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26029 Q213K NC_045512.2:g.637C>A YP_009724391.1:p.Gln213Lys open reading frame 3a gene (SARS-CoV-2) orf3a gene (SARS-CoV-2) open reading frame 3a protein (SARS-CoV-2) Orf3a protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*01:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26029 Q213K NC_045512.2:g.637C>A YP_009724391.1:p.Gln213Lys open reading frame 3a gene (SARS-CoV-2) orf3a gene (SARS-CoV-2) open reading frame 3a protein (SARS-CoV-2) Orf3a protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to A*01:01-restricted CD8+ ORF3a epitope, which is otherwise 'consistently dominant and of high magnitude'. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26256 F4F NC_045512.2:g.12C>T YP_009724392.1:p.Phe4Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26268,26269,26270 T9I,T9I,T9I NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~300 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26268,26269,26270 T9I,T9I,T9I NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26296 L18I NC_045512.2:g.52C>A YP_009724392.1:p.Leu18Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (47x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26299 L19F NC_045512.2:g.55C>T YP_009724392.1:p.Leu19Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26312 F23C NC_045512.2:g.68T>G YP_009724392.1:p.Phe23Cys envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~8.8 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26314 V24M NC_045512.2:g.70G>A YP_009724392.1:p.Val24Met envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26319 V25V NC_045512.2:g.75A>G YP_009724392.1:p.Val25Val envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (45x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26333 T30I NC_045512.2:g.89C>T YP_009724392.1:p.Thr30Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26353 L37F NC_045512.2:g.109C>T YP_009724392.1:p.Leu37Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26395 L51I NC_045512.2:g.151C>A YP_009724392.1:p.Leu51Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (47x overrepresentation vs expected count of ~24 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26416 V58L NC_045512.2:g.172G>C YP_009724392.1:p.Val58Leu envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26428 V62F NC_045512.2:g.184G>T YP_009724392.1:p.Val62Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (18x overrepresentation vs expected count of ~333 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26442 N66K NC_045512.2:g.198T>G YP_009724392.1:p.Asn66Lys envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~23 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26447 S68F NC_045512.2:g.203C>T YP_009724392.1:p.Ser68Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26447 S68C NC_045512.2:g.203C>G YP_009724392.1:p.Ser68Cys envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (58x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26456 P71R NC_045512.2:g.212C>G YP_009724392.1:p.Pro71Arg envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26467 V75L NC_045512.2:g.223G>C YP_009724392.1:p.Val75Leu envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (3762.7x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526 A2S NC_045512.2:g.4G>T YP_009724393.1:p.Ala2Ser membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (38x overrepresentation vs expected count of ~334 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526 A2S NC_045512.2:g.4G>T YP_009724393.1:p.Ala2Ser membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) immunosuppression variant emergence Emergent as 16% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing. Avanzato 2020 https://doi.org/10.1016/j.cell.2020.10.049 doi:10.1016/j.cell.2020.10.049 pmid:33248470 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526,26527,26529 D3H,D3H,D3H NC_045512.2:g.7G>C,NC_045512.2:g.7G>C,NC_045512.2:g.7G>C YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (227x overrepresentation vs expected count of ~14 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26528,26528,26528 A2A,A2A,A2A NC_045512.2:g.6A>T,NC_045512.2:g.6A>G,NC_045512.2:g.6A>C YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (25x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26530 D3G NC_045512.2:g.8A>G YP_009724393.1:p.Asp3Gly membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (31x overrepresentation vs expected count of ~53 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26542 T7I NC_045512.2:g.20C>T YP_009724393.1:p.Thr7Ile membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 pmid:33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26546 I8I NC_045512.2:g.24T>C YP_009724393.1:p.Ile8Ile membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~80 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26573,26576,26577 Q19E,Q19E,Q19E NC_045512.2:g.55C>G,NC_045512.2:g.55C>G,NC_045512.2:g.55C>G YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~8 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26620 C33S NC_045512.2:g.98G>C YP_009724393.1:p.Cys33Ser membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~32 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26645 N41N NC_045512.2:g.123C>T YP_009724393.1:p.Asn41Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (19x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26681 F53F NC_045512.2:g.159C>T YP_009724393.1:p.Phe53Phe membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (163x overrepresentation vs expected count of ~567 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26730 V70L NC_045512.2:g.208G>C YP_009724393.1:p.Val70Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26748 I76V NC_045512.2:g.226A>G YP_009724393.1:p.Ile76Val membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26748 I76L NC_045512.2:g.226A>C YP_009724393.1:p.Ile76Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~9 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26749 I76T NC_045512.2:g.227T>C YP_009724393.1:p.Ile76Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (19x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26767 I82T NC_045512.2:g.245T>C YP_009724393.1:p.Ile82Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) homoplasy This mutation presents mainly within the B.1 (44.0%) and B.1.525 (38.1%) lineages. Currently, 99.7% of the B.1.525 lineage isolates carry the M:I82T mutation. While this mutation is scattered across multiple phylogenetic clades, most cases cluster in two recent clades, suggesting a likely selective advantage in certain haplotype backgrounds. Shen 2021 https://doi.org/10.1080/22221751.2021.1922097 doi:10.1080/22221751.2021.1922097 pmid:33896413 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26767 I82T NC_045512.2:g.245T>C YP_009724393.1:p.Ile82Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (67x overrepresentation vs expected count of ~42 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26801,26801,26801 L93L,L93L,L93L NC_045512.2:g.279C>G,NC_045512.2:g.279C>A,NC_045512.2:g.279C>T YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~628 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26855,26858 F112F,F112F NC_045512.2:g.336C>T,NC_045512.2:g.336C>T YP_009724393.1:p.Phe112Phe,YP_009724393.1:p.Phe112Phe membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~463 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26861 N113N NC_045512.2:g.339T>C YP_009724393.1:p.Asn113Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (57x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26873 N117N NC_045512.2:g.351C>T YP_009724393.1:p.Asn117Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26882,26882 L120L,L120L NC_045512.2:g.360C>A,NC_045512.2:g.360C>T YP_009724393.1:p.Leu120Leu,YP_009724393.1:p.Leu120Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26894,26894 L124L,L124L NC_045512.2:g.372C>T,NC_045512.2:g.372C>G YP_009724393.1:p.Leu124Leu,YP_009724393.1:p.Leu124Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26895 H125Y NC_045512.2:g.373C>T YP_009724393.1:p.His125Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) homoplasy In experimental models of SARA_CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26895 H125Y NC_045512.2:g.373C>T YP_009724393.1:p.His125Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (22x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26907,26909,26909 L129L,L129L,L129L NC_045512.2:g.385C>T,NC_045512.2:g.387G>A,NC_045512.2:g.387G>T YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26927 E135E NC_045512.2:g.405A>G YP_009724393.1:p.Glu135Glu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (232x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26951,26951,26951 V143V,V143V,V143V NC_045512.2:g.429G>C,NC_045512.2:g.429G>A,NC_045512.2:g.429G>T YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~508 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26966 H148H NC_045512.2:g.444T>C YP_009724393.1:p.His148His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26972 R150R NC_045512.2:g.450T>C YP_009724393.1:p.Arg150Arg membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~89 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26985 H155N NC_045512.2:g.463C>A YP_009724393.1:p.His155Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26987 H155H NC_045512.2:g.465T>C YP_009724393.1:p.His155His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27021 E167Q NC_045512.2:g.499G>C YP_009724393.1:p.Glu167Gln membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27035,27038 T172T,T172T NC_045512.2:g.516A>G,NC_045512.2:g.516A>G YP_009724393.1:p.Thr172Thr,YP_009724393.1:p.Thr172Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27059 Y179Y NC_045512.2:g.537C>T YP_009724393.1:p.Tyr179Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27112 S197T NC_045512.2:g.590G>C YP_009724393.1:p.Ser197Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (18x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27134 Y204Y NC_045512.2:g.612T>C YP_009724393.1:p.Tyr204Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27143 N207N NC_045512.2:g.621C>T YP_009724393.1:p.Asn207Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27147 D209H NC_045512.2:g.625G>C YP_009724393.1:p.Asp209His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (81x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27367 Q56X NC_045512.2:g.166C>T YP_009724394.1:p.Gln56Xaa open reading frame 6 gene (SARS-CoV-2) orf6 gene (SARS-CoV-2) open reading frame 6 protein (SARS-CoV-2) Orf6 protein (SARS-CoV-2) IFN activity The residues listed are determinants of the potent IFN-antagonistic activity of SARS-CoV-2 ORF6 (via blocking mRNA nuclear export) Kimura 2020 https://doi.org/10.2139/ssrn.3690468 doi:10.2139/ssrn.3690468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28144 L84S NC_045512.2:g.251T>C YP_009724396.1:p.Leu84Ser open reading frame 8 gene (SARS-CoV-2) orf8 gene (SARS-CoV-2) open reading frame 8 protein (SARS-CoV-2) Orf8 protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 pmid:33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28307,28309,28310,28311 P13L,P13L,P13L,P13L NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13). de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28307,28309,28310,28311 P13L,P13L,P13L,P13L NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28310 P13S NC_045512.2:g.37C>T YP_009724397.2:p.Pro13Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*27:05. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28310 P13S NC_045512.2:g.37C>T YP_009724397.2:p.Pro13Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13). de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28769 T166A NC_045512.2:g.496A>G YP_009724397.2:p.Thr166Ala nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) variant linear antibody epitope effects Confers a significant PIWAS value decrease (reduced antigenicity) Haynes 2020 https://doi.org/10.1101/2020.11.23.20235002 doi:10.1101/2020.11.23.20235002 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28853 S194T NC_045512.2:g.580T>A YP_009724397.2:p.Ser194Thr nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 pmid:33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28854 S194L NC_045512.2:g.581C>T YP_009724397.2:p.Ser194Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) outcome hazard ratio In March 2021 this variant had an allele frequency of 47.62 and 7.25% in deceased patients, compared to 35.16 and 3.20% of the same variant in recovered patients, from the Gujarat and global datasets. Joshi 2021 https://doi.org/10.3389/fgene.2021.586569 doi:10.3389/fgene.2021.586569 pmid:33815459 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28854 S194L NC_045512.2:g.581C>T YP_009724397.2:p.Ser194Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) homoplasy Mutation with a population frequency of 30% in a Mexican dataset, primarily of lineage 20B, but also present in a substantial number of 20A lineage sequences, suggesting convergent evolution. Barona-Gomez 2021 https://doi.org/10.1101/2021.05.18.21256128 doi:10.1101/2021.05.18.21256128 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28869 P199L NC_045512.2:g.596C>T YP_009724397.2:p.Pro199Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021 https://doi.org/10.1101/2021.08.05.455082 doi:10.1101/2021.08.05.455082 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28879 S202R NC_045512.2:g.606T>G YP_009724397.2:p.Ser202Arg nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows major increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021 https://doi.org/10.1101/2021.08.05.455082 doi:10.1101/2021.08.05.455082 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28881 R203M NC_045512.2:g.608G>T YP_009724397.2:p.Arg203Met nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows most increase in RNA content of any N mutation tested, suggesting that this mutation improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021 https://doi.org/10.1101/2021.08.05.455082 doi:10.1101/2021.08.05.455082 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28977 S235F NC_045512.2:g.704C>T YP_009724397.2:p.Ser235Phe nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) variant linear antibody epitope effects Substantially increases epitope and antigen scores in 2 of 579 individuals (should increase immune response). In the B1.1.7 lineage this is largely counteracted by the D3L mutation, which decreases PIWAS signal significantly in 1.5% of COVID patients, for a net neutral effect at the population level. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29239,29239 M322I,M322I NC_045512.2:g.966G>A,NC_045512.2:g.966G>T YP_009724397.2:p.Met322Ile,YP_009724397.2:p.Met322Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. Agerer 2021 https://doi.org/10.1126/sciimmunol.abg6461 doi:10.1126/sciimmunol.abg6461 pmid:33664060 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29247 T325I NC_045512.2:g.974C>T YP_009724397.2:p.Thr325Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29247 T325I NC_045512.2:g.974C>T YP_009724397.2:p.Thr325Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes partial loss of T cell line responsiveness and CTL killing ability by B*40:01-restricted CD8+ N epitope MEVTPSGTWL 322-331. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29266,29266 L331F,L331F NC_045512.2:g.993G>T,NC_045512.2:g.993G>C YP_009724397.2:p.Leu331Phe,YP_009724397.2:p.Leu331Phe nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. Agerer 2021 https://doi.org/10.1126/sciimmunol.abg6461 doi:10.1126/sciimmunol.abg6461 pmid:33664060 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is 'consistently dominant and of high magnitude'. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2:g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is 'consistently dominant and of high magnitude'. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2:g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29409 T379I NC_045512.2:g.1136C>T YP_009724397.2:p.Thr379Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 335 R24C NC_045512.2:g.70C>T YP_009724389.1:p.Arg24Cys YP_009724389.1:Arg24Cys open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (25x overrepresentation vs expected count of 514 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 347 V28I NC_045512.2:g.82G>A YP_009724389.1:p.Val28Ile YP_009724389.1:Val28Ile open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (30x overrepresentation vs expected count of 143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 383 S40P NC_045512.2:g.118T>C YP_009724389.1:p.Ser40Pro YP_009724389.1:Ser40Pro open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~58 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 396 Q44L NC_045512.2:g.131A>T YP_009724389.1:p.Gln44Leu YP_009724389.1:Gln44Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~19 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 443 V60I NC_045512.2:g.178G>A YP_009724389.1:p.Val60Ile YP_009724389.1:Val60Ile open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 489 D75G NC_045512.2:g.224A>G YP_009724389.1:p.Asp75Gly YP_009724389.1:Asp75Gly open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 490,490 D75E,D75E NC_045512.2:g.225T>G,NC_045512.2:g.225T>A YP_009724389.1:p.Asp75Glu,YP_009724389.1:p.Asp75Glu YP_009724389.1:Asp75Glu,YP_009724389.1:Asp75Glu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~20 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) immunosuppression variant emergence Emergent as 22% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing. Avanzato 2020 https://doi.org/10.1016/j.cell.2020.10.049 doi:10.1016/j.cell.2020.10.049 pmid:33248470 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) IFN activity Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 500-523) was tested in vitro for IFN response. Lin 2021 https://doi.org/10.1016/j.chom.2021.01.015 doi:10.1016/j.chom.2021.01.015 pmid:33548198 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) IFN activity Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-517) was tested in vitro for IFN response. Lin 2021 https://doi.org/10.1016/j.chom.2021.01.015 doi:10.1016/j.chom.2021.01.015 pmid:33548198 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) IFN activity Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-523) was tested in vitro for IFN response. Lin 2021 https://doi.org/10.1016/j.chom.2021.01.015 doi:10.1016/j.chom.2021.01.015 pmid:33548198 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,509,518 M85V,M85V,M85V NC_045512.2:g.253A>G,NC_045512.2:g.253A>G,NC_045512.2:g.253A>G YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val YP_009724389.1:Met85Val,YP_009724389.1:Met85Val,YP_009724389.1:Met85Val open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 508 H81Q NC_045512.2:g.243T>A YP_009724389.1:p.His81Gln YP_009724389.1:His81Gln open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (30x overrepresentation vs expected count of ~20 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 510 M85K NC_045512.2:g.254T>A YP_009724389.1:p.Met85Lys YP_009724389.1:Met85Lys open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~12 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 561 R99H NC_045512.2:g.296G>A YP_009724389.1:p.Arg99His YP_009724389.1:Arg99His open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 563 S100C NC_045512.2:g.298A>T YP_009724389.1:p.Ser100Cys YP_009724389.1:Ser100Cys open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (33x overrepresentation vs expected count of ~19 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 593 H110Y NC_045512.2:g.328C>T YP_009724389.1:p.His110Tyr YP_009724389.1:His110Tyr open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (22x overrepresentation vs expected count of ~514 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 593 H110D NC_045512.2:g.328C>G YP_009724389.1:p.His110Asp YP_009724389.1:His110Asp open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~11 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 606 I114T NC_045512.2:g.341T>C YP_009724389.1:p.Ile114Thr YP_009724389.1:Ile114Thr open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (155x overrepresentation vs expected count of ~58 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 657 A131V NC_045512.2:g.392C>T YP_009724389.1:p.Ala131Val YP_009724389.1:Ala131Val open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~514 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 677 A138T NC_045512.2:g.412G>A YP_009724389.1:p.Ala138Thr YP_009724389.1:Ala138Thr open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 761 S166G NC_045512.2:g.496A>G YP_009724389.1:p.Ser166Gly YP_009724389.1:Ser166Gly open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (132x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 798 N178S NC_045512.2:g.533A>G YP_009724389.1:p.Asn178Ser YP_009724389.1:Asn178Ser open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay From 014d4a9ec26ae675d317ae505c2f382476a7b751 Mon Sep 17 00:00:00 2001 From: Madeline Iseminger <32916719+miseminger@users.noreply.github.com> Date: Tue, 12 Nov 2024 19:05:55 -0800 Subject: [PATCH 096/161] Delete assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.0.tsv --- ...kay_functionalAnnotation_SARSCoV2_v4.0.tsv | 1388 ----------------- 1 file changed, 1388 deletions(-) delete mode 100644 assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.0.tsv diff --git a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.0.tsv b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.0.tsv deleted file mode 100644 index 8838d515..00000000 --- a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.0.tsv +++ /dev/null @@ -1,1388 +0,0 @@ -"organism" "reference accession" "reference database name" "nucleotide position" "original mutation description" "nucleotide mutation" "amino acid mutation" "amino acid mutation alias" "gene name" "gene symbol" "protein name" "protein symbol" "measured variant functional effect" "inferred variant functional effect" "viral life cycle functional effect" "variant functional effect description" "CVX code" "DrugBank Accession Number" "Antibody Registry ID" "author" "publication year" "URL" "DOI" "PMID" "peer review status" "curator" "mutation functional annotation resource" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has a 0.66x fold change in EC50 value with Remdesivir." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "viral load" "" "" "This mutant causes a 0.41x fold change in the infectious virus production rate." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has a 0.27x fold change in EC50 value with Remdesivir." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has an inhibition rate of virus production by Remdesivir of 0.80." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutant has an inhibition rate of virus production by Remdesivir of 0.78." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "1703" "F480L" "NC_045512.2:g.1438T>C" "YP_009724389.1:p.Phe480Leu" "YP_009724389.1:Phe300Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "viral load" "" "" "This mutant causes a 0.48x fold change in the infectious virus production rate." "" "" "" "Torii" "2022" "https://doi.org/10.1101/2022.02.22.481436" "doi:10.1101/2022.02.22.481436" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.526 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,22992,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed 3.8x reduction in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,21846,22317,22319,22320,23012,23399,23401,23402,23403,23664" "L5F,T95I,D253G,D253G,D253G,E484K,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,22992,23012,23664" "L5F,S477N,E484K,A701V" "NC_045512.2:g.13C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 114 test-positive were Iota. Two dose vaccine efficacy against Iota was 95.7 (81.7-99.0%), one dose VE was 88.8 (0.7-98.7)%." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21575,25186" "L5F,Q1208H" "NC_045512.2:g.13C>T,NC_045512.2:g.3624G>T" "YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Gln1208His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Four of the convalescent sera tested showed 4-fold or greater improvement in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21587" "P9S" "NC_045512.2:g.25C>T" "YP_009724390.1:p.Pro9Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2M28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21597" "S12F" "NC_045512.2:g.35C>T" "YP_009724390.1:p.Ser12Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "A variant in low % circulation, predicted to have a similar effect to the experimentally verified S12P, which introduces a new signal peptide, altering cleavage to occur between residues C15 and V16, thereby eliminating the C15-C136 disulfide bond – similarly to escape mutants at positions C15 and C136. This in turn decreases to varying degrees N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600" "S13I" "NC_045512.2:g.38G>T" "YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The S13I mutation dampened binding of 5 mAbs and abrogated binding of 5 additional mAbs out of 11 neutralizing mAbs evaluated. Predicted to shift the signal peptide cleavage site from S13-Q14 to C15-V16, which can affect NTD conformation. PG: in saying S12F does not shift the signal peptide nor affect mAb binding, this manuscript appears to contradict the text of McCallum et al.'s earlier 2021 manuscript stating that S12F *does* affected some mAb binding via putative signal peptide shift." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018" "S13I,W152C" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The B.1.427/B.1.429 S13I/W152C NTD did not bind to any NTD-directed neutralizing mAbs, which are known to target a single antigenic site (antigenic site i), whereas binding of the non-neutralizing S2L20 mAb to the NTD antigenic site iv was not affected by any mutants, confirming proper retention of folding." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Lineages bearing these spike mutations comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the 'California' or 'West Coast' variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI:1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020." "" "" "" "Peng" "2021" "https://doi.org/10.1093/cid/ciab283" "doi:10.1093/cid/ciab283" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 9 plasma collected 15 to 28 days after early 2020 infections, neutralization reduced 4.9-fold for B.1.427/B.1.429 compared to wildtype (D614G). In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.427/B.1.429 pseudotyped virus, as well as WT and other VOCs." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Swab samples N/NP viral RNA is approximately 2-fold higher in B.1.427/B.1.429 than in non-variant viruses." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "14 of 34 RBD-specific mAbs showed reduced neutralization to the B.1.427/B.1.429 variant pseudotype." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Antibody neutralization assays showed 6.7-fold resistance against 7/8 convalescent plasma." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.249 (1.7-fold). Neutralization against 10 convalescent plasma was somewhat poorer (3.1-fold)." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917" "S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using HIV pseudotype: Neutralization potency of 11 Moderna mRNA1273-elicited plasma (7-27 days post-2nd dose) was reduced ~2.8-fold compared to wildtype (D614G) S. It was reduced ~4-fold in 14 Pfizer/BioNtech BNT162b2-elicited plasma (7-27 days post-2nd dose). Using VSV pseudotype: we observed a 3-fold average reduction of Pfizer/BioNtech BNT162b2-elicited plasma neutralizing activity." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "6 of 11 (55%) vaccine recipients (Moderna or Pfizer), showed 2x reduction in neutralization to a B.1.429 lineage virus." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.427/429 reduced 2.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 2.7x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 2.3x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21600,22018,22915,22916,22917,23399,23401,23402,23403,25135" "S13I,W152C,L452R,L452R,L452R,D614G,D614G,D614G,D614G,K1191N" "NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3573G>T" "YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys1191Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for CAL.20C (B.1.429), and a slight decrease in CD8+ percentage (p=0.0201) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21604,21604" "Q14H,Q14H" "NC_045512.2:g.42G>C,NC_045512.2:g.42G>T" "YP_009724390.1:p.Gln14His,YP_009724390.1:p.Gln14His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21605" "C15R" "NC_045512.2:g.43T>C" "YP_009724390.1:p.Cys15Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21606" "C15F" "NC_045512.2:g.44G>T" "YP_009724390.1:p.Cys15Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite 'i', but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates neutralization by N-terminal-domain-targeting mAbs 4-19. Impairs neutralization by N-terminal-domain-targeting mAbs 4A8 and 2-17." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614" "L18F" "NC_045512.2:g.52C>T" "YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggetsing that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132" "L18F,T20N,P26S,D138Y,R190S" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The neutralization titer of NTD-binding mAb159 was 133-fold reduced on P.1 compared to Victoria (~wild type), with only 64% neutralization at 10 μg/mL. Residues 20, 18, and 138 form a cluster underlying the 245–259 loop, which inserts into a groove between the light and heavy chains of Fab 159. In addition, the N-terminal residues preceding residue 18 interact with the antibody and may be perturbed. Given that there is likely a single supersite ('i') for potent NTD-binding antibodies, the binding of many of these are likely affected. Using 20 potent (primaruly anti-RBD) antibodies, neutralization was measured by a focus reduction neutralization test (FRNT) and compared with neutralization of Victoria (~wild type) and variants B.1.1.7 and B.1.351. Compared to Victoria neutralization by the mAbs was significantly impacted by P.1, with 12/20 showing > 10-fold reduction in FRNT50 titer and a number showing complete knockout of activity. The results with P.1 showed a greater impact compared to B.1.1.7 but were, as expected, similar to those with B.1.351." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 12 Moderna vaccinee sera 15 days post second dose (43 days since first vaccination), an average 2.8x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 4.8x decrease against the full P.1 type vs WA-1 was observed, though overall with a higher ID50 reciprocal value. In 10 Pfizer vaccinee sera 7 days or more post second dose (28 days or more since first vaccination), an average 2.2x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.8x decrease against the full P.1 type vs WA-1 was observed, with similar variant ID50 reciprocal value." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the “up” position." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Amongst RBD-targeting Emergency Use Authorized monoclonal antibody treatments CB6, LY-CoV555 and REGN10933 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1, but REGN10987 activity remains strong. RBD-targeting monoclonal antibodies 2-15 and C121 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. N terminal domain targeting monoclonal antibodies 5-7, 4-8, 4-18 and 2-17 have abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In convalescent sera one month or more post-infection in Spring 2020, an average 6.5x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.4x decrease against the full P.1 type vs WA-1 was observed, with better full P.1 ID50 reciprocal value compared to the 10-mutation model." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.03.01.433466" "doi:10.1101/2021.03.01.433466" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Three healthcare workers (29-50yo) had confirmed P.1 [Gamma] re-infection in the Amazonas region of Brazil 3-9 months after initial infection from viruses with distinct lineage from P.1, but mild symptoms upon re-infection and evidence for infectiousness during re-infection." "" "" "" "Naveca" "2021" "https://doi.org/10.21203/rs.3.rs-318392/v1" "doi:10.21203/rs.3.rs-318392/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "After a 128 day interval, a patient in Sao Paulo State, Brazil reinfected with P.1 (first episode likely predates P.1 emergence). Both cases were fairly mild (difficulty breathing, tiredness, dizziness and fatigue)." "" "" "" "Malta Romano" "2021" "https://doi.org/10.1590/S1678-9946202163036" "doi:10.1590/S1678-9946202163036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 3.0x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 349 test-positive were Gamma. Two dose vaccine efficacy against Gamma was 95.5 (90.9-97.8%), one dose VE was 74.2 (43.8-88.1%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Gamma (P.1) variant is 0.6x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 4.1x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x cleavage of S2 relative to WA1 (D614G) wildtype by Gamma variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but H655Y is upstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.7 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0039 for mild resistance." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Unlike wild type or B.1.1.7, P.1 lineage virus was able to infect and replicate in common lab mouse strains, with high titer." "" "" "" "Montagutelli" "2021" "https://doi.org/10.1101/2021.03.18.436013" "doi:10.1101/2021.03.18.436013" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.248 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07. B.1.1.248 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.248 variant constellation in 10 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples, P=0.0020." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly lower against B.1.1.248 variant constellation in sera tested from most of the 15 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 16.6% in this B.1.1.248 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped P.1 virus has reduced neutralization activity vs wild type: 6.7x (30 sera Pfizer median 9 days post 2nd dose) and 4.5x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Among 46,884 HCWs in Manaus, Brazil vaccinated with at least one dose of CoronaVac, a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%; 95% CI, 11.3 - 71.4) in the odds of symptomatic SARS-CoV-2 infection was observed during the period 14 days or more after receiving the first dose. Estimated vaccine effectiveness of at least one dose against any SARS-CoV-2 infection was 35.1% (95% CI, −6.6 - 60.5) in the same time period." "" "" "" "Hitchlings" "2021" "https://doi.org/10.1101/2021.04.07.21255081" "doi:10.1101/2021.04.07.21255081" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for P.1 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the P.1 variants used, using the most popular as a stand in]" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "VSV pseudotype P.1 showed 4.8-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections)." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype P.1 showed slight decrease in cell entry relative to wild type in 262T and 263T-ACE2 (kidney) cell lines. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Neutralizing antibodies that were generated following a mild infection with SARS-CoV-2 B.1.128 were effective in vitro, and likely protective, against the SARS-CoV-2 P.1. variant in the majority of individuals based on 60 convalescent sera tested." "" "" "" "Mendes-Correa" "2021" "https://doi.org/10.1101/2021.05.11.21256908" "doi:10.1101/2021.05.11.21256908" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.15x *increase* in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "VSV pseudotype P.1 entry mediated by the S proteins of the P.1 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Cell fusion proficiency was slight impaired. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "P.1 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with Lilly mAb combination LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of P.1. There was also escape from neutralization of P.1 by REGN10933 (one of 2 in Regeneron's mAb cocktail) and a modest reduction in neutralization of P.1 by AstraZeneca's AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized P.1 with all reaching a plateau at 100% neutralization; interestingly, ADG30 showed a slight increase of neutralization of P.1. S309 Vir was largely unaffected, although for several viruses, including P.1, the antibody failed to completely neutralize, conceivably reflecting incomplete glycosylation at N343, since the sugar interaction is key to binding of this antibody." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "PBMCs of 11 mild COVID-19 patients collected 38-80 days after symptom onset were stimulated with the 15-mer peptide pools (w/ 10 residue overlaps) from the wholle viral proteome, showing no significant CD4+ cell count effect for P.1, and a slight increase in CD8+ percentage (p=0.0195) by Activation Induced Marker (AIM) assay (cellular immunity measurement). [in the text, this increase is not noted as signficant, even though p=0.05 is used elsewhere in the text as a signficance threshold]" "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against P.1 at various time points using pseudovirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 85%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,22812,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525,24642,25088" "L18F,T20N,P26S,D138Y,R190S,K417T,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 256 for B.1.1.7 virus. Compare to somewhat stronger neutralization titer for wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21621,21638,21974,22132,23012,23060,23061,23062,23063,23399,23401,23402,23403,23521,23522,23524,23525" "L18F,T20N,P26S,D138Y,R190S,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The relative transmissibility of P.1 estimated at the national level (Italy) varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. PG: variant list has been abbreviated due to mixed K417 bases in this lineage, potential miscalls of deletions" "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21762,21763,21764,21765,21766,21766,21761,21801,22206,22334,22600,22600,22810,22811,22812,22813,22813,22879,22881,22882,22882,22986,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,H69del,H69del,H69del,H69del,H69del,H69del,V70del,D80A,D215G,W258R,R346S,R346S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,A475V,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.772T>C,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1424C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ala475Val,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments and mutations from variants of concern completely ablates neutralization in 19 of 21 convalescents plasma collected mean 1.3 months post infection. [actual Y145del from manuscript substituted with more common Y144del description]" "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801" "L18F,D80A" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The L18F and D80A of the B.1.351 lineage lead to reconfiguration of the N-terminal segment despite the disulfide between Cys16 and Cys136 that partly anchors the N-terminal peptide. The most consequential changes are probably from the triple residue deletion... which causes a shift of the nearby loop 144-155 and must also reconfigure the adjacent disorder loop (residues 246-260), both of which form part of the neutralizing epitopes...bringing large changes in the antigenic surface in this region." "" "" "" "Cai" "2021" "https://doi.org/10.1101/2021.04.13.439709" "doi:10.1101/2021.04.13.439709" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The 501Y.V2 to first wave IC50 ratio ranged from 6 to 200-fold. Averaging across all 7 participant convalescent sera highlighted the dramatic decrease in sensitivity to neutralization of authentic 501Y.V2 variants. PG: I'm purposefully ignoring D614G and A701V as contributors" "" "" "" "Cele" "2021" "https://doi.org/10.1038/s41586-021-03471-w" "doi:10.1038/s41586-021-03471-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike)." "" "" "" "Riddell" "2021" "https://doi.org/10.1101/2021.04.17.440246" "doi:10.1101/2021.04.17.440246" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pzifer vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1), but were all infected before 14 days post second vaccination." "" "" "" "Kustin" "2021" "https://doi.org/10.1101/2021.04.06.21254882" "doi:10.1101/2021.04.06.21254882" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In human sera 8 weeks post-vaccination with INO-4800, a ~7-fold reduction in B.1.351 neutralization was observed." "" "" "" "Andrade" "2021" "https://doi.org/10.1101/2021.04.14.439719" "doi:10.1101/2021.04.14.439719" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23593,23593,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.04.13.439482" "doi:10.1101/2021.04.13.439482" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "B.1.351 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of B.1.351. There was also escape from neutralization of B.1.351 by REGN10933 and a modest reduction in neutralization of B.1.351 by AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized B.1.351." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.07x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "[Contrary to how this paper has been cited, Voysey et al. do NOT show evidence of decreased effectiveness of ChAdOx1 (AstraZeneca) against the South African B.1.351 lineage. Insufficient numbers reaching the primary study endpoint were available in that arm of the vaccine study to report any statistics from the South African participants. Additionally, the study period of the paper ended in November 2020, while the earliest reported case of this lineage is October (covariants.org), only becoming dominant by mid-November.]" "" "" "" "Voysey" "2021" "https://doi.org/10.1016/S0140-6736(20" "doi:10.1016/S0140-6736(20" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 0.036x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR22 molecule had a 1.57x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.054x fold change in IC50 in B.1.351 Beta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.351 sample. Contrast this with 1.4-fold reduction for just the pseudovirus combination of 'key' B.1.351 mutations K417N+E484K+N501Y. WA1 and B.1.351 FRNT50 titers correlated weakly at the individual level, with some individual’s serum potently neutralizing WA1 while having FRNT50 for B.1.351 below the assay limit of detection (1:20)." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v2 virus has reduced neutralization activity vs wild type: 41.2x (30 sera Pfizer median 9 days post 2nd dose) and 20.8x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed for B.1.351 a CD4+ cell count decrease (29%, p=0.00063) as well as CD8+ (33%, p=0.0016) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants." "" "" "" "Shinde" "2021" "https://doi.org/10.1056/NEJMoa2103055" "doi:10.1056/NEJMoa2103055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Beta neutralizing antibodies is 0.899x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: while B.1.1.7 and D614G showed neutralization by nasal swab from only one different previously infected vacinee neutralizing at weeks 3 and 6, B.1.351 showed zero neutralization at either time point in any sample (and relatively impaired serum neutralization)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Beta neutralizing antibodies is 0.803x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Beta Variant B.1.351 RBD significantly better than w.t. SARS-CoV-2 RBD. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals (5/9) and recipients of a only a single dose of mRNA vaccine (10/11) – heterotypic neutralization dropped to negligible levels, particularly against B.1.351." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "A 1.8-fold drop in FRNT50 for B.1.351 was observed in 44 sera collected between 1 and 301 post-infection." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "3.2x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing]" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 6.3x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Encouragingly, we find that the majority of T cell responses in recipients of two doses of the BNT162b2 vaccine are generated by epitopes that are invariant between the [wildtype] and two of the current variants of concern (B.1.1.7 and B.1.351). In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals and recipients of a only a single dose of mRNA vaccine – heterotypic neutralization dropped to negligible levels, particularly against B.1.351." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 16/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.351, with similar results for the live virus." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.351. We observed an increase (relative to D614G) in binding of soluble ACE2 to B.1.351, and to a much gearter extent to B.1.1.7, which both carry the N501Y mutation (see Fig 3)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Sera from individuals who have been infected with Delta does not have strong neutralising activity against Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 8 for B.1.351 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Pseudotype lentivirus for the full B.1.351 Spike variant list shows increase affinity for ACE2 as measured by IC50. This is in contrast to B.1.1.7 which showed no major change, indicating that the shared N501Y mutation is the driver of affinity change, attentuated in the B.1.1.7 mutatioon set, but maintained in the B.1.351 lineage." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 8.2x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.351 pseudotyped virus model ablates neutralization by RBD-directed mAbs CB6, 4-20, 2-4, 2-43, 910-30, 2-302-15, LY-Cov555, C121. B.1.351 pseudotyped virus model severely impairs neutralization by RBD-directed mAb 1-20. B.1.351 pseudotyped virus model impairs neutralization by RBD-directed mAb REGN10933. B.1.351 pseudotyped virus model ablates neutralization by N-terminal-domain-directed mAbs 5-24, 4-8, 4A8, 4-19. B.1.351 pseudotyped virus model severely impairs neutralization by N-terminal-domain-directed mAb 2-17. B.1.351 pseudotyped virus model impairs neutralization by N-terminal-domain-directed mAb 5-7. PG: Live virus data for the same mAbs is similar, but 1-20 becomes severally impaired, REGN10933 activity is ablated, and Brii-196 becomes impaired." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type)." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v2 reduced 7.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms had mean ~6x reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 99.7x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664,21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V,T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T,NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "DARPin SR16m molecule had a 6.7x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with all key mutations from B.1.351 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting some synergy between the mutations to decrease cell entry fitness (i.e. cell entry is liklely not the driver of this lineage's dominance)." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22206,23060,23061,23062,23063,22810,22811,22812,22813,22813,23012,23399,23401,23402,23403" "L18F,D80A,D215G,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The most significant loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against authentic B.1.351 lineage virus (9.2-fold). Neutralization against 10 convalescent plasma was poorer (18.7x)." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "L18F,D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks." "" "" "" "Meister" "2021" "https://doi.org/10.1093/infdis/jiab260" "doi:10.1093/infdis/jiab260" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication]" "" "" "" "Ribas Freitas" "2021" "https://doi.org/10.1101/2021.04.13.21255281" "doi:10.1101/2021.04.13.21255281" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the Parana state of Brazil, patients aged 20-29 years experienced a tripling of their case fatality rate (CFR), from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling comparing February to January in 2021. Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil. [this is somewhat indirect evidence that assume greatly increasing proportion of P.1 cases in March (70%) compared to February, but the first official ID of P.1 in Parana state (Feb 16th) may be due to testing procedures rather than actual prevalence]" "" "" "" "Santos de Oliviera" "2021" "https://doi.org/10.1101/2021.03.24.21254046" "doi:10.1101/2021.03.24.21254046" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21614,22915,22916,22917,23060,23061,23062,23063,23521,23522,23524,23525" "L18F,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.52C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 (Pfizer) vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains." "" "" "" "Mallm" "2021" "https://doi.org/10.1101/2021.04.27.21254849" "doi:10.1101/2021.04.27.21254849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Delta (B.1.617.2) shows mean 2.1x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22224,22227,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,A222V,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Delta (B.1.617.2) shows 3.64x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22916,22917,23012,23399,23401,23402,23403" "T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this lineage defining mutation combination from B.1.617.3 conferred a ~4.5x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22916,22917,23012,23399,23401,23402,23403" "T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this lineage defining mutation combination from B.1.617.3 conferred a ~11.8x drop in neutralization (NT50) [suggesting role for T19R and T95I in half the sera]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,22915,22916,22917,23012,23399,23401,23402,23403" "T19R,T95I,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this lineage defining mutation combination from B.1.617.3 increased syncytium formation ~2.3x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21846,23399,23401,23402,23403" "T19R,T95I,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23604,23399,23401,23402,23403,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,P681R,D614G,D614G,D614G,D614G,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4.5x cleavage of S2 relative to WA1 (D614G) wildtype by Delta (B.1.617.2) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~3.5x for closely related Kappa B.1.617.1 also with P681R at the cleavage site)." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 ('Kappa') reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. [Mutation list in publication appears to contain a typo with R158del instead of R158G]" "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 4.0x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Modelling the Delta variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increased 11x relative to wild type (15.3 vs 1.4). [del ~157 truncated due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a coinfection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.020x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 2.6x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.10x fold change in IC50 in B.1.617.2 Delta" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22915,22916,22917,22992,22995,23399,23401,23402,23403,24410" "T19R,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In primary human airway epithelial cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 1.9x relative to wild type (2.7 vs 1.4). This is the Delta variant with the P681R furin cleavage site mutation absent. [del ~157 truncated due to ambiguity]" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Plasma neutralizing activity was also assessed against SARS-CoV-2 Delta, Omicron BA.1, BA.2 and BA.4/5 variants using viruses pseudotyped with appropriate variant spikeproteins. Delta breakthrough infection resulted in 15-fold increased neutralizing titers." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Delta neutralizing antibodies is 0.872x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Delta neutralizing antibodies is 0.952x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Plasma neutralizing activity in 49 participants was measured using HIV-1 pseudotyped with the 100 WT SARS-CoV-2 spike protein. Delta breakthrough infection resulted in 11-fold increased geometric mean half-maximal neutralizing titer (NT50)." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Delta Variant B.1.617.2 RBD or w.t. SARS-CoV-2 RBD with nearly equal potency determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 507 pM for binding to the Delta B.1.617.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present." "" "" "" "Fowlkes" "2021" "https://doi.org/10.15585/mmwr.mm7034e4" "doi:10.15585/mmwr.mm7034e4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.92x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%." "" "" "" "Nanduri" "2021" "https://doi.org/10.15585/mmwr.mm7034e3" "doi:10.15585/mmwr.mm7034e3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.08.11.21261885" "doi:10.1101/2021.08.11.21261885" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001)." "" "" "" "Chia" "2021" "https://doi.org/10.1101/2021.07.28.21261295" "doi:10.1101/2021.07.28.21261295" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "The incidence rate of Covid-19 during the Delta-dominant period (Jul-Aug 2021) was lower for late vaccinated (49.0/1000 person-years) [formerly placebo] versus early vaccinated (77.1/1000 person-years) participants in the Moderna mRNA-1273 Phase 3 trials, representing a 36.4% VE reduction (95% CI 17.1%-51.5%). There were fewer severe Covid-19 cases in the late group (6; 6.2/1000 person-years) than early (13; 3.3/1000 person-years), representing a 46.0% reduction (95% CI −52.4%-83.2%). Three Covid-19 related hospitalizations occurred with two resulting deaths in the early group." "" "" "" "Baden" "2021" "https://doi.org/10.1101/2021.09.17.21263624" "doi:10.1101/2021.09.17.21263624" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccination of health care workers in Delhi was started in early 2021, with the ChdOx-1 (Astra Zeneca) vaccine. Surveillance has suggested B.1.1.7 dominance in the Delhi area during early 2021, with growth of B.1.617 since March 2021. During the wave of infections during March and April an outbreak of SARS-CoV-2 was confirmed in 33 vaccinated staff members at a single tertiary centre (age 27-77 years). Sequencing revealed that 16/33 were B.1.617.2, with a range of other B lineage viruses including B.1.1.7 for the rest except one A lineage case. Importantly no severe cases were documented in this event." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death." "" "" "" "" "2021" "https://doi.org/10.1503/cmaj.211248" "doi:10.1503/cmaj.211248" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.2 aka Delta) showed a 2.34x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance." "" "" "" "Twohig" "2021" "https://doi.org/10.1016/S1473-3099(21" "doi:10.1016/S1473-3099(21" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Denmark, for the period Jan 1 to Jun 27, 2021, Delta variant was associated with increased an risk ratio of 2.83 [95% CI 2.02–3.98] for hospitalization." "" "" "" "Bager" "2021" "https://doi.org/10.1016/S1473-3099(21" "doi:10.1016/S1473-3099(21" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.89x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Delta Molnupiravir (MK-4482) had ~4x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Case 62541 cluster in Singapore included a fully vaccinated nurse 2 months post-vaccine [likely Pfizer based on dates and supply], and a doctor of unknown vaccine status. This cluster was caused by a B.1.617.2 virus [via crossreference to" "" "" "" "" "" "nan" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Delta (B.1.617.2) has an IC50 fold change of 46.5x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Delta (B.1.617.2) has an IC50 fold change of 0.15x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Delta (B.1.617.2) has an IC50 fold change of 0.57x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Delta (B.1.617.2) has an IC50 fold change of 0.87x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,22028,22034,22915,22916,22917,22992,22995,23399,23401,23402,23403,23604,24410,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "T19R,R158G,R158G,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.56C>G,NC_045512.2:g.467_472del,NC_045512.2:g.472A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.2848G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Delta (B.1.617.2) variant is 0.6x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21618,23399,23401,23402,23403" "T19R,D614G,D614G,D614G,D614G" "NC_045512.2:g.56C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21627" "T22I" "NC_045512.2:g.65C>T" "YP_009724390.1:p.Thr22Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain, frequently observed in various human infection lineages, reduces the tropism of SARS-CoV-2 in F81 (cat kidney, Felis catus) and BHK-21 (golden hamster kidney, Mesocricetus auratus) cell line cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21648" "T29I" "NC_045512.2:g.86C>T" "YP_009724390.1:p.Thr29Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21717,21762,21763,21764,21765,21766,21766,21761,23012,23399,23401,23402,23403,23593,23593,24224" "Q52R,H69del,H69del,H69del,H69del,H69del,H69del,V70del,E484K,D614G,D614G,D614G,D614G,Q677H,Q677H,F888L" "NC_045512.2:g.155A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C" "YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.525 reduced 4.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21717,23012,23593,23593,24224" "Q52R,E484K,Q677H,Q677H,F888L" "NC_045512.2:g.155A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C,NC_045512.2:g.2662T>C" "YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The B.1.525 appears to have poor transmissibility when in competition with B.1.1.7 and other circulating strains in Denmark (early 2021)." "" "" "" "Albertsen" "2021" "https://www.covid19genomics.dk/2021-05-08_data-overview.html#b1525" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21752,21752" "W64R,W64R" "NC_045512.2:g.190T>A,NC_045512.2:g.190T>C" "YP_009724390.1:p.Trp64Arg,YP_009724390.1:p.Trp64Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21759" "H66R" "NC_045512.2:g.197A>G" "YP_009724390.1:p.His66Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent, especially on a D614 wildtype background." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduces neutralization by structurally unmapped mAb COVA1-21 (cluster XI)." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No notable change in neutralization efficiency, despite N439K by itself showing a ~2x decrease on average in 16 health workers' convalescent sera." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This deletion outside the receptor binding domain in pseudotyped VSV promoted the capacity of pseudotyped VSV to transduce black flying fox (Pteropus alecto) kidney PabKi.1 cells (17.8%) to a level twice that of human epithelial-like Huh-7 cells (9.8%)" "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization activity of almost all convalescent sera tested decreased ~2x." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization activity of convalescent sera tested decreased ~2x with this B.1.1.7 pseudotyped virus." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Neutralization activity of almost all Moderna Phase 1 sera tested actually *increased*." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761" "H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "The delH69/V70 enhances viral infectivity, indicating its effect on virus fitness is independent to the N501Y RBM change [with which it is found in lineage B.1.1.7] Possibly arisen as a result of the virus evolving from immune selection pressure in infected individuals and possibly only one chronic infection in the case of lineage B.1.1.7." "" "" "" "Kemp" "2020" "https://doi.org/10.1101/2020.12.14.422555" "doi:10.1101/2020.12.14.422555" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron (a.k.a. B.1.1.529) Spike pseudotyped VSV and Vero E6 cells has somewhat reduced neutralization (2.7x) vs wild type with monoclonal antibody Sotrovimab (a.k.a. VIR-7831). [delins at 214 omitted for syntax compatibility]" "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,21987,21990,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23040,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron breakthrough infection after 3-dose vaccination resulted in a further 3.5-fold and 2.9-fold increase of Omicron BA.1 and BA.2 neutralizing titers. Omicron BA.4/5 showed the highest neutralization resistance of all variants tested, resulting in low geometric mean neutralizing titers in plasma samples obtained after the second vaccine dose (NT50=72)." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Delta variant and was used to determine neutralizing antibodytitres. There was a 24.63x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 4.21x fold increase in antibody response pre-reinfection. There was a 39.27x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against B.1 variant and was used to determine neutralizing antibodytitres. There was a 6.76x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 2.06x fold increase in antibody response pre-reinfection. There was a 8.18x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron B.1.1.529 (BA.1) neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Omicron BA.1 variant is 1.0x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigms’ ACE-2 variant LVE/STR chimera binds to SARS-2 Omicron variant B.1.1.529 spike protein trimer with high affinity. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Omicron BA.1 has an IC50 fold change of 0.38x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 73 pM for binding to the Omicron B.1.1.529. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron (B.1.1.529 [BA.1]) have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "All 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 729 NT50." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "All 10 individuals with 3 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 3319 NT50." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.1 has an IC50 fold change of 0.30x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Omicron BA.1 has an IC50 fold change of 1.26x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Omicron variant and was used to determine neutralizing antibodytitres. There was a 114.84x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 6.61x fold increase in antibody response pre-reinfection. There was a 1194.9x fold increase in antibody response during reinfection." "" "" "" "Shete" "2022" "https://doi.org/10.1101/2022.05.12.491584" "doi:10.1101/2022.05.12.491584" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23048,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604,24130" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,G496S,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H,N856K" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1486G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2568C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.1 has an IC50 fold change of 0.08x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.3 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22679,22686,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S373P,S375F,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.3 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was somewhat lower against B.1.1.7 in sera tested from most of the 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.7 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2489." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,21987,21990,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.1.7 sample. Contrast this with 1.3-fold reduction for just the pseudovirus combination of 'key' B.1.1.7 mutation N501Y." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing moderate decrease in infection rate amongst the cells, significantly lower than the deletion or Y453F alone, or their combination, suggesting a synergistic effect on poorer human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild to modest decrease in infection rate amongst the cells, suggesting a net mild negative effect on human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, much closer to D614G activity level than Y453F alone, suggesting compensatory effects between the deletion and the mutation in human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920,23399,23401,23402,23403,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F,D614G,D614G,D614G,D614G,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.298 virus has reduced neutralization activity vs wild type: 1.4x (30 sera Pfizer median 9 days post 2nd dose) and 1.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from Mink Cluster 5 was neutralized more easily than D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with all key mutations from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (~50%) decrease in infection rate amongst the cells, suggesting that this anthropozoonotic event is driven by other factors at the expense of human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,22920,25249,25249,25249" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,Y453F,M1229I,M1229I,M1229I" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1358A>T,NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells, markedly higher infectivity than either mutation alone, suggesting a synergistic net neutral effect on human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7+E484K reduced 2.8x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Compare with 1.2x reduction for B.1.1.7 without E484K." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23012,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,E484K,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization capacity GMT of 27 subjects' sera post-infection was markedly worse against B.1.1.7 + E484K than the lineage alone, with a 11.4x drop." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "In comparison of B.1.1.7 lineage (193 cases) vs. 'wildtype' (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo." "" "" "" "van Loon" "2021" "https://doi.org/10.1101/2021.04.15.21255389" "doi:10.1101/2021.04.15.21255389" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "A higher proportion of cases infected with the B.1.1.7 variant were hypoxic on admission compared to other variants (70.0% vs 62.5%, p=0.029), in London between March 13th 2020 and February 17th 2021 (400 B.1.1.7 cases out of 1470 total sequenced)." "" "" "" "Snell" "2021" "https://doi.org/10.1101/2021.03.16.21253377" "doi:10.1101/2021.03.16.21253377" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x). PG: these effects are laregly missing in the deletion-alone data" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation combination causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, moreso than this combination with the addition of P681H." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020. Possible reinfections were identified in 249 (0.7% [95% CI 0.6-0.8]) of 36509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants." "" "" "" "Graham" "2021" "https://doi.org/10.1016/s2468-2667(21" "doi:10.1016/s2468-2667(21" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined" "" "" "" "Haas" "2021" "https://doi.org/10.1016/S0140-6736(21" "doi:10.1016/S0140-6736(21" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease." "" "" "" "Emary" "2021" "https://doi.org/10.2139/ssrn.3779160" "doi:10.2139/ssrn.3779160" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion)." "" "" "" "Marquez" "2021" "https://doi.org/10.1017/ice.2021.195" "doi:10.1017/ice.2021.195" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant." "" "" "" "Hall" "2021" "https://doi.org/10.1016/S0140-6736(21" "doi:10.1016/S0140-6736(21" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Second infection in December 2020 with B.1.1.7 after April 2020 initial infection with B.2 in a 78-year-old man with a history of Type 2 diabetes mellitus, diabetic nephropathy on hemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnea, ischemic heart disease, with no history of immunosuppression." "" "" "" "Harrington" "2021" "https://doi.org/10.1093/cid/ciab014" "doi:10.1093/cid/ciab014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots." "" "" "" "Woldemeskel" "2021" "https://doi.org/10.1172/JCI149335" "doi:10.1172/JCI149335" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Alpha (B.1.1.7) variant is 1.0x fold the wildtype in 42 COVI." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.1.7. We observed a dramatic increase (relative to D614G) in binding of soluble ACE2 to B.1.1.7, and to a lesser extent to B.1.351, which both carry the N501Y mutation (see Fig 3)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant." "" "" "" "Hall" "2021" "https://doi.org/10.1016/S0140-6736(21" "doi:10.1016/S0140-6736(21" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.]" "" "" "" "Amit" "2021" "https://doi.org/10.1016/S0140-6736(21" "doi:10.1016/S0140-6736(21" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks." "" "" "" "Meister" "2021" "https://doi.org/10.1093/infdis/jiab260" "doi:10.1093/infdis/jiab260" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively." "" "" "" "Schuit" "2021" "https://doi.org/10.1093/infdis/jiab171" "doi:10.1093/infdis/jiab171" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1136/bmj.n1088" "doi:10.1136/bmj.n1088" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE)." "" "" "" "Loconsole" "2021" "https://doi.org/10.1016/j.cmi.2021.05.007" "doi:10.1016/j.cmi.2021.05.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Alpha (B.1.1.7) has an IC50 fold change of 1.19x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Alpha Molnupiravir (MK-4482) had ~2.75x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The sera of 16 individuals with time course collection was evaulated against VSV pseudotypes: neutralized D614G at week 2, whereas B.1.1.7 started to be neutralized at week 3, although less efficiently than D614G. B.1.1.7 and D614G strains were similarly neutralized at week 4 (1 week after booster dose)." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed." "" "" "" "Tarke" "2021" "https://doi.org/10.1101/2021.02.27.433180" "doi:10.1101/2021.02.27.433180" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus." "" "" "" "Sapkal" "2021" "https://doi.org/10.1093/jtm/taab051" "doi:10.1093/jtm/taab051" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the 47D10. Alpha (B.1.1.7) has an IC50 fold change of 0.40x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2.5x cleavage of S2 relative to WA1 (D614G) wildtype by Alpha variant variant as measured by mass spectrometry of Vero-TMPRSS culture." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.39x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "NTD-specific nAbs showed a substantial (3-450x) decrease in neutralization potency against the recently reported highly transmissible B.1.1.7 variant of concern, whereas RBD-specific nAbs were either unaffected or showed lower decreases in potency." "" "" "" "Graham" "2021" "https://doi.org/10.1016/j.immuni.2021.03.023" "doi:10.1016/j.immuni.2021.03.023" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20x resistence to mAb CQ038 by B.1.1.7 pseudotyped virus" "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 2/20 (10%) samples showed >10x reduction (sera collected ~1mo post Jan 2020 first wave in China). Neutralizing antibody titers of 8/20 samples (40%) decreased below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM for binding to the Alpha B1.1.7. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 2.6x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Lessens the potency of mAbs COVA2-17 (~5x, similar to N501Y alone), COVA1-12 (~11x) and COVA1-21 (>100x), which do not compete allosterically." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.7 pseudotyped virus model impairs binding by RBD-directed mAb 910-30. B.1.1.7 pseudotyped virus model abolishes N-terminal-domain-directed mAbs 5-24, 4-8, and 4A8. B.1.1.7 pseudotyped virus model impairs binding by N-terminal-domain-directed mAbs 2-17, 4-19, 5-7." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%)." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Modelling the Alpha variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 3.9x relative to wild type (5.4 vs 1.4). This is less efficient than Delta (11x vs wildtype using a P681R mutation instead). [del ~144 changed due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a co-infection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.08.12.456173v3" "doi:10.1101/2021.08.12.456173v3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant." "" "" "" "Lopez Bernal" "2021" "https://doi.org/10.1056/NEJMoa2108891" "doi:10.1056/NEJMoa2108891" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization assays of B.1.1.7 virus showed a reduction of 2.5-fold (14 days post 2nd dose AstraZeneca, n=15), 2.1-fold (28 days post 2nd dose AstraZeneca, n=10), and 3.3-fold (7-17 days post 2nd dose Pfizer-BioNTech, n=25). [D1119H was included in the original paper, assumed typographical error and changed to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 1 (B.1.1.7) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 virus has reduced neutralization activity vs wild type: 2.1x (30 sera Pfizer median 9 days post 2nd dose) and 2.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Note that Y145del was actually noted in the paper as the effect of their DNA construct, but this is equivalent at the protein level to the more commonly annotated Y144del." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM analysis of B.1.1.7 demonstrates an increased propensity for 'up', receptor accessible conformation of the Spike protein trimer." "" "" "" "Cai" "2021" "https://doi.org/10.1101/2021.04.13.439709" "doi:10.1101/2021.04.13.439709" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Alpha Variant B.1.1.7 RBD significantly better than GenScript IgG FL18-740 w.t. ACE-2 mAB. Determined using Surrogate Viral Neutralization Tests." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "NVX-CoV2373 [Novavax] vaccine in phase 3 trial was 89.7% (95% CI, 80.2-94.6) effective in preventing COVID-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8-99.5) and 86.3% (71.3-93.5) against the prototype strain and B.1.1.7 variant, respectively." "" "" "" "Heath" "2021" "https://doi.org/10.1101/2021.05.13.21256639" "doi:10.1101/2021.05.13.21256639" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera." "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Live virus was tested ex vivo in reconstituted brochial epithelium, and out competed wild type." "" "" "" "Touret" "2021" "https://doi.org/10.1101/2021.03.22.436427" "doi:10.1101/2021.03.22.436427" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 1.7x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "clinical indicators" "" "" "After adjusting for the age factor, in a prospective Chinese cohort study B.1.1.7 variant infection (compared to B.1.140) was the risk factor for C-reactive protein (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), Serum amyloid A (0.011, 5.031, [1.459, 17.354]), Creatine Kinase (0.034, 4.34, [0.05, 0.91]), CD4+ T lymphocyte (0.029, 3.31, [1.13, 9.71]), and Ground Glass Opacity (0.005, 5.418, [1.656, 17.729])" "" "" "" "Song" "2021" "https://doi.org/10.1101/2021.05.04.21256655" "doi:10.1101/2021.05.04.21256655" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given]" "" "" "" "Puranik" "2021" "https://doi.org/10.1101/2021.08.06.21261707" "doi:10.1101/2021.08.06.21261707" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "aerosolization" "" "" "Alpha variant cases in a large campus study showed fine-aerosol shedding amongst unmasked participants remained significantly greater for alpha variant infections (18-fold, 95% CI, 3.4 to 92-fold) after adjusting for the increased viral RNA in MTS and saliva, the number of coughs during sampling sessions, and symptom. After controlling for the effect of masks and numbers of coughs during sampling, alpha variant infection was associated with a 100-fold (95% CI, 16 to 650-fold) increase in coarse- and a 73-fold (95% CI, 15 to 350-fold) increase in fine-aerosol RNA shedding." "" "" "" "Adenaiye" "2021" "https://doi.org/10.1093/cid/ciab797" "doi:10.1093/cid/ciab797" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "We observed a sharp decline in cases when ∼50% of the elderly population was 2 weeks beyond their first vaccination dose and at a time point during which the B.1.1.7 variant gained transmission dominance. In support of this finding, it was suggested that, after the first vaccination dose, more than 70% of patients develop neutralization antibodies,15 and the vaccine efficiency can reach 85%." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.44x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "First documented cases of domestic cat and dog infections with the B.1.1.7 strain." "" "" "" "Hamer" "2021" "https://doi.org/10.1111/tbed.14122" "doi:10.1111/tbed.14122" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "," "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,23709,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,T716I,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.1.7 lineage effectiveness was observed as 29.5% (95% CI [22.9,35.5]) against infection, and 54.1% against severe/critical/fatal disease (95% CI [26.1-71.9]). Two weeks or more after 2nd dose, effectiveness climbed to 89.5% [85.9,92.3] against infection, and 100% against severe/critical/fatal disease (95% CI [81.7,100])." "" "" "" "" "" "," "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24506" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,S982A" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Lilly's LY-CoV16 showed marked reduction in neutralization of B.1.1.7." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23604,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,P681H,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Sera neutralized the B1.1.7 isolate with a lower potency (2-fold; 95% CL: 1.5 – 3-fold), and those with the lowest homotypic neutralizing potency had undetectable heterotypic potency (2/25)." "" "" "" "Skelly" "2021" "https://doi.org/10.21203/rs.3.rs-226857/v1" "doi:10.21203/rs.3.rs-226857/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23399,23401,23402,23403,23709,23604,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,T716I,P681H,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T,NC_045512.2:g.2042C>A,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific replication effects" "" "" "In this report, by using a lower infectious dose, we demonstrate that B.1.1.7 (cultured sample Hong Kong/HKPU-00015/2021) exhibits higher infectivity and/or replication efficiency in the nasal epithelium. (Hamster model of infection)" "" "" "" "Mok" "2021" "https://doi.org/10.1101/2021.04.19.440414" "doi:10.1101/2021.04.19.440414" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks." "" "" "" "Munitz" "2021" "https://doi.org/10.1016/j.xcrm.2021.100264" "doi:10.1016/j.xcrm.2021.100264" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 'wild type' SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples." "" "" "" "Couzens" "2021" "https://doi.org/10.1101/2021.04.02.21254832" "doi:10.1101/2021.04.02.21254832" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Based on 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020, Rt of B.1.1.7 was 1.35x (95% CI 1.02-1.69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant." "" "" "" "Graham" "2021" "https://doi.org/10.1016/s2468-2667(21" "doi:10.1016/s2468-2667(21" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036)." "" "" "" "Song" "2021" "https://doi.org/10.1101/2021.05.04.21256655" "doi:10.1101/2021.05.04.21256655" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older." "" "" "" "Nyberg" "2021" "https://doi.org/10.48550/arXiv.2104.05560" "doi:10.48550/arXiv.2104.05560" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7." "" "" "" "Graham" "2021" "https://doi.org/10.1016/s2468-2667(21" "doi:10.1016/s2468-2667(21" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "The mortality hazard ratio associated with infection with [B.1.1.7] compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community (54906 matched pairs of participants who tested positive for SARS-CoV-2 in pillar 2 between 1 October 2020 and 29 January 2021). In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases." "" "" "" "Challen" "2021" "https://doi.org/10.1136/bmj.n579" "doi:10.1136/bmj.n579" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38])." "" "" "" "Frampton" "2021" "https://doi.org/10.1016/s1473-3099(21" "doi:10.1016/s1473-3099(21" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralization capacity GMT of 27 subjects' sera post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies." "" "" "" "Muik" "2021" "https://doi.org/10.1126/science.abg6105" "doi:10.1126/science.abg6105" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age." "" "" "" "Bager" "2021" "https://doi.org/10.2139/ssrn.3792894" "doi:10.2139/ssrn.3792894" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases)." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "20/29 sera after the first dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 variant of 3.2 ± 5.7. After the second dose, the GMT was markedly increased compared with the first-dose titres, with a fold change of 1.9 ± 0.9 (mean ± s.d.). Neutralization GMT of 27 subjects post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country." "" "" "" "Davies" "2021" "https://doi.org/10.1126/science.abg3055" "doi:10.1126/science.abg3055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load." "" "" "" "Lyngse" "2021" "https://doi.org/10.1101/2021.04.16.21255459" "doi:10.1101/2021.04.16.21255459" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models." "" "" "" "Lamers" "2021" "https://doi.org/10.1101/2021.05.03.441080" "doi:10.1101/2021.05.03.441080" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity." "" "" "" "Nyayanit" "2021" "https://doi.org/10.1101/2021.04.30.442222" "doi:10.1101/2021.04.30.442222" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66)." "" "" "" "Stefanelli" "2021" "https://doi.org/10.1101/2021.04.06.21254923" "doi:10.1101/2021.04.06.21254923" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49)" "" "" "" "Buchan" "2021" "https://www.medrxiv.org/content/10.1101/2021.03.31.21254502v1" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype B.1.1.7 showed no significant difference in cell entry relative to wild type in 6 cell lines. Cell fusion proficiency was unchanged." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community." "" "" "" "Davies" "2021" "https://doi.org/10.1038/s41586-021-03426-1" "doi:10.1038/s41586-021-03426-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants." "" "" "" "Lindstrøm" "2021" "https://doi.org/10.1101/2021.03.29.21254122" "doi:10.1101/2021.03.29.21254122" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 ('UK variant'). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H." "" "" "" "Ratcliff" "2021" "https://doi.org/10.1101/2021.02.24.21251989" "doi:10.1101/2021.02.24.21251989" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x)." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, but to a smaller extent than N501Y and the deletion alone." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Slight neutralization improvement on average in 16 health workers' convalescent sera." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "These key B.1.1.7 mutations as a combination neutralized slightly less well than D614G and this was noticeable in the lack of sera with high neutralizing titer for the viruses across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23604" "H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,P681H" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,23399,23401,23402,23403,22915,22916,22917" "H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 17.2x-fold lower (95% CI: 0.6x-0.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,22679,23521,23522,23524,23525,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,23071,23074,23075,22992,22995,22810,22811,22812,22813,22813,23018,22576,22577,22578,22783,22784,22785,22786,22786,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,21761,23399,23401,23402,23403,22915,22916,22917" "H69del,H69del,H69del,H69del,H69del,H69del,S373P,H655Y,H655Y,H655Y,H655Y,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,Y505H,Y505H,Y505H,T478K,T478K,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1117T>C,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1456T>G,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.204_209del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 13.0-fold lower (95% CI: 4.2x-4.6x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,22810,22811,22812,22813,22813,23009,23010,23012,23013" "H69del,H69del,H69del,H69del,H69del,H69del,K417N,K417N,K417N,K417N,K417N,E484A,E484A,E484A,E484A" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In Ontario, using a retrospective matched case (age, gender and onset date) study of 6,312 Omicron cases vs 8,875 Delta, the adjusted risk of hospitalization or death was 54% lower (HR=0.46, 95%CI: 0.27, 0.77) among Omicron cases, after adjusting for vaccination statis and time since 2nd shot. The ratio for >60yo was 0.55 (95%CI: 0.28-1.06), and <60yo was 0.30 (95%CI: 0.16-0.57)." "" "" "" "Ulloa" "2021" "https://doi.org/10.1101/2021.12.24.21268382" "doi:10.1101/2021.12.24.21268382" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21762,21763,21764,21765,21766,21766,23009,23010,23012,23013" "H69del,H69del,H69del,H69del,H69del,H69del,E484A,E484A,E484A,E484A" "NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection, evidenced by a reinfection hazard ratio of 2.39 (CI95: 1.88-3.11) relative to primary infection in the initial part of South Africa's 4th covid-19 wave (November 2021). In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. [minimal variant signature for Omicron (B.1.1.529) used based on H69del PCR dropout observed in November 2021 coincident with the rise of Omicron]" "" "" "" "Pulliam" "2021" "https://doi.org/10.1101/2021.11.11.21266068" "doi:10.1101/2021.11.11.21266068" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800" "D80N" "NC_045512.2:g.238G>A" "YP_009724390.1:p.Asp80Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800" "D80Y" "NC_045512.2:g.238G>T" "YP_009724390.1:p.Asp80Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This AA substitution outside the receptor binding domain in pseudotyped VSV promoted a 7.2% transduction rate in golden hamster cells, which was higher than that of human epithelial-like Huh-7 cells (6.6%)." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21800,22188,22206,22597,22599,23012,23521,23522,23524,23525,23604" "D80Y,I210del,D215G,R346K,R346K,E484K,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.238G>T,NC_045512.2:g.629_631del,NC_045512.2:g.644A>G,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp80Tyr,YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.VOI.V2 (first identified in Angola) reduced 8.0x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "One individual of 30 in the study, with HLA supertype HLA*A24:02, had a linear epitope that overlaps this variant of concern." "" "" "" "Redd" "2021" "https://doi.org/10.1101/2021.02.11.21251585" "doi:10.1101/2021.02.11.21251585" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolishes neutralizing activity of N-terminal-domain-directed mAb 4-19." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801" "D80A" "NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated that there is no free energy change (ddG) for this variant (i.e. same stability as wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In an Ontario long term care facility, cumulatively, weaker BNT162b2 vaccine stimulation, age/comorbidities, produced a ∼130-fold reduction in apparent neutralization titers in mean 88yo LTCH residents against Beta (B.1.351), relative to staff vaccinees against D614G wild type. 37.9% of 116 two-dose-mRNA-vaccinated residents had undetectable neutralizing antibodies to B.1.351. mRNA-1273 vaccinee sera displayed ~2 better neutralization than BNT162b2. [common defining B.1.351 mutations noted, as the manuscript does not provide details]" "" "" "" "Abe" "2021" "https://doi.org/10.1101/2021.08.06.21261721" "doi:10.1101/2021.08.06.21261721" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, 7 of 15 neutralized this B.1.351 pseudotype that includes the L242del, and only one had titers above 100. Only one of the 15 sera achieved 80% neutralization. [compare to 5 and 1 for pseudotype without the deletion]" "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Detectable antibodies against B.1.351 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 71%, Day 209 54%. Detectable antibodies against B.1.351 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 79%, Day 209 58%. Detectable antibodies against B.1.351 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 63%, Day 43 100%, Day 119 71%, Day 209 79%. Decreased neutralization on some assays was seen especially in those vaccinees tested that were 71+." "" "" "" "Pegu" "2021" "https://doi.org/10.1101/2021.05.13.444010" "doi:10.1101/2021.05.13.444010" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~10-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~3 fold without the deletion] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were significant, but ~500x weaker than in previously infected patients after first dose." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "A two-dose regimen of (AstraZeneca) ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, vaccine efficacy against severe Covid-19 is undetermined." "" "" "" "Madhi" "2021" "https://doi.org/10.1101/2021.02.10.21251247" "doi:10.1101/2021.02.10.21251247" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "humoral response durability" "" "" "In a prospective study of 107 hospitalized patients, decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7 and P.1 variants for at least 6 months (last of two samples taken) in patients previously hospitalized for COVID-19. A weaker protection was however observed for the B.1.351 variant." "" "" "" "Betton" "2020" "https://doi.org/10.1093/cid/ciab308" "doi:10.1093/cid/ciab308" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used)." "" "" "" "Gallagher" "2021" "https://doi.org/10.1101/2021.05.03.442455" "doi:10.1101/2021.05.03.442455" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Beta (B.1.351) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination." "" "" "" "" "" "nan" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 34 convalescent cases 4–9 weeks following infection in June 2020, before the emergence of B.1.1.7, neutralization titers against B.1.351 were, on average, 13.3-fold reduced compared with an early Victoria sample (p < 0.0001). Significantly, 18 of 34 samples failed to reach 50% neutralization at a plasma dilution of 1:20, with a number showing a near total reduction of neutralization activity. In 13 convalescent cases 4–9 weeks following infection with B.1.1.7, neutralization titers against B.1.351 were, on average, 3.1-fold reduced compared with an early Victoria sample (p < 0.0001)." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Beta (B.1.351) variant is 0.4x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Unlike wild type or B.1.1.7, B.1.351 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. PG: The virus used in these expriments has a non-typical deletion+sub in the 242 region." "" "" "" "Montagutelli" "2021" "https://doi.org/10.1101/2021.03.18.436013" "doi:10.1101/2021.03.18.436013" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.1.351-v3 reduced 8.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The B.1.351 variant constellation causes an ∼20-fold increase in affinity for ACE2 compared with Wuhan RBD, which may influence transmissibility." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001)." "" "" "" "Zhou" "2021" "http://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x cleavage of S2 relative to WA1 (D614G) wildtype by Beta variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but A701V is downstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Beta (B.1.351) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine plasma neutralization of B.1.351-spike virus was nominally robust but lower (~3x) than other variants of concern." "" "" "" "Liu" "2021" "https://doi.org/10.1056/NEJMc2102017" "doi:10.1056/NEJMc2102017" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Testing against B.1.351 the 20 most effective mAbs (19 anti-RBD, 1 anti-NTD) from a screen of 377 against wild type, 4 of 20 antibodies had >10-fold fall in neutralization titers, with most of these showing a complete knockout of activity. This is in line with the key roles of K417, E484, and N501, in particular E484, in antibody recognition of the ACE2 interaction surface of the RBD. Regeneron mAb cocktail: The neutralization of REGN10987 was unaffected by B.1.351, while REGN10933 was severely impaired (773-fold). AstraZeneca mAb cocktail: Neutralization by the AZ pair of antibodies was little affected on B.1.351 compared with Victoria." "" "" "" "Zhou" "2021" "https://doi.org/10.1016/j.cell.2021.02.037" "doi:10.1016/j.cell.2021.02.037" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Beta Molnupiravir (MK-4482) had ~1.75x fold drop." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v1 virus has reduced neutralization activity vs wild type: 34.5x (30 sera Pfizer median 9 days post 2nd dose) and 27.7x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "On average across 7 European countries studied, using B.1.351 defining mutations: Significant shift to infection in those without pre-existing conditions (79.6% vs 89% for non-VOC cases). Significant increase in hospitalization rate (19.3% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.3% vs 0.6% for non-VOC cases). PG: seems to be different notations around the LAL deletion, using the minimal shared definition to catch as many as possible." "" "" "" "Funk" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348" "doi:10.2807/1560-7917.ES.2021.26.16.2100348" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Beta (B.1.351) has an IC50 fold change of 0.88x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "Compared to Alpha (B.1.1.7) variant, odds of progressing to severe disease were 1.24-fold (95% CI: 1.11-1.39) higher for Beta. Odds of progressing to critical disease were 1.49-fold (95% CI: 1.13-1.97) higher. Odds of COVID-19 death were 1.57-fold (95% CI: 1.03-2.43) higher." "" "" "" "Abu-Raddad" "2021" "https://doi.org/10.1101/2021.08.02.21261465" "doi:10.1101/2021.08.02.21261465" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Beta (B.1.351) has an IC50 fold change of 0.15x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using B.1.351 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~3-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~10 fold with L242del] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were signficiant, but >100x weaker than in previously infected patients after first dose." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664,23399,23401,23402,23403" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, one third (5/15) of sera neutralized this B.1.351 pseudotype and only three had ID50 titers above 100. Only two of the 15 sera achieved 80% neutralization." "" "" "" "Stamatatos" "2021" "https://doi.org/10.1126/science.abg9175" "doi:10.1126/science.abg9175" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Inoculation with the B.1.351 isolate resulted in lower clinical scores in 6 rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. Our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity." "" "" "" "Munster" "2021" "https://doi.org/10.1101/2021.05.07.443115" "doi:10.1101/2021.05.07.443115" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission." "" "" "" "Yinda" "2021" "https://doi.org/10.1101/2021.05.05.442780" "doi:10.1101/2021.05.05.442780" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22206,22810,22811,22812,22813,22813,23664,23060,23061,23062,23063,23012" "D80A,D215G,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.239A>C,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.2102C>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "4 health care workers in the 20's and 30's with no underlying conditions and seropositivity or confirmed 2020 SARS-CoV-2 infections were confirmed to have B.1.351 infection during a Februrary 2021 hospital outbreak in Luxembourg. Symptoms were mostly mild on first infection, and milder on second infection." "" "" "" "Staub" "2021" "https://doi.org/10.2807/1560-7917.ES.2021.26.18.2100423" "doi:10.2807/1560-7917.ES.2021.26.18.2100423" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "During an outbreak of SARS-CoV-2 501Y.V2 in a nursing home, all non-vaccinated residents (5/5) versus half of those fully vaccinated 2-5 weeks prior with BNT162b2 (13/26) were infected. Two of 13 vaccinated versus 4 of 5 non-vaccinated residents presented severe disease. BNT162b2 did not prevent the outbreak, but reduced transmission and disease severity. Among the 13 fully vaccinated residents who were infected, 2 (15.4%) presented with an asymptomatic disease, 9 (69.2%) developed mild to moderate symptoms, and 2 (15.4%) progressed to severe disease with fatal evolution secondary to acute respiratory distress syndrome (ARDS). There was no relationship between anti-S antibody levels at diagnosis and disease severity. Overall, the proportion of residents with severe disease in the non-vaccinated group (4/5) was higher than that in the vaccinated group (2/13). Only 1 vaccinated staff, but 10 unvaccinated were infected in the outbreak (no severe disease)." "" "" "" "Bailly" "2021" "https://doi.org/10.1093/cid/ciab446" "doi:10.1093/cid/ciab446" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped B.1.351 v3 virus has reduced neutralization activity vs wild type: 42.4x (30 sera Pfizer median 9 days post 2nd dose) and 19.2x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "B.1.1.351 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. B.1.1.351 variant constellation ablates Class 3 N-terminal domain targeting antibodies COV2-2489 and COV2-2676 (the only two tested)." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.351 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0020 for moderate resistance." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera." "" "" "" "Wang" "2021" "https://doi.org/10.1056/NEJMc2103022" "doi:10.1056/NEJMc2103022" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "B.1.1.351 in 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In a Syrian hamster model, B.1.351 variant virus had >4x reduction in YRNT90 (measure of neutralization) using wild type convalescent sera. PG: Note that exact sequence for B.1.351 used was not disclosed." "" "" "" "Cochin" "2021" "https://doi.org/10.1101/2021.04.19.440435" "doi:10.1101/2021.04.19.440435" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1)." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres." "" "" "" "Huang" "2021" "https://doi.org/10.1101/2021.02.01.429069" "doi:10.1101/2021.02.01.429069" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens." "" "" "" "Röltgen" "2021" "https://doi.org/10.1101/2021.04.05.21254952" "doi:10.1101/2021.04.05.21254952" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was significantly lower against B.1.351 in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4)" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer" "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.351 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the B.1.351 variants used, using the most popular as a stad in]" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H]" "" "" "" "Supasa" "2021" "https://doi.org/10.1016/j.cell.2021.02.033" "doi:10.1016/j.cell.2021.02.033" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "VSV pseudotype B.1.351 showed 7.86-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections)." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.351 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Vaccine elicited antibodies neutralized virus with the B.1.351 spike protein had an average 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abrogates Bamlanivimab, Etesevimab, or their combined use neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In one of eight cell lines tested (293T lung cells), a modest increase in cell entry was observed." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "VSV pseudotype B.1.351 showed slight decrease in cell entry relative to wild type in 263T-ACE2 (kidney) cell line, and slight increase in Calu-3 (lung). Cell fusion proficiency was slight impaired." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "VSV pseudotype B.1.351 entry mediated by the S proteins of the B.1.351 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.cell.2021.03.036" "doi:10.1016/j.cell.2021.03.036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.351 lineage effectiveness was observed as 16.9% (95% CI [10.4,23.0]) against infection, and 0% against severe/critical/fatal disease (95% CI [0-19.0]). Two weeks or more after 2nd dose, effectiveness climbed to 75.0% [70.5,78.9] against infection, and 100% against severe/critical/fatal disease (95% CI [73.7,100])." "" "" "" "" "" "," "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "" "" "" "" "" "" "," "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2)." "" "" "" "Leier" "2021" "https://doi.org/10.1101/2021.04.25.21256049" "doi:10.1101/2021.04.25.21256049" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21801,22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23664" "D80A,K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,A701V" "NC_045512.2:g.239A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Approximately 6-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction." "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846" "T95I" "NC_045512.2:g.284C>T" "YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "65yo female with no severe Covid-19 risk factors tested positive 36 days after second dose of BNT162b2 (Pfizer) vaccine. Presented with fatigue, sinus congestion, and a headache developed; her symptoms plateaued and began to resolve six days later. [Mising genome coverage in regions of Spike covering clinically relevant mutations K417T, L452R, E484K, A701V, D796H, N501Y]" "" "" "" "Hacisuleyman" "2021" "https://doi.org/10.1056/NEJMoa2105000" "doi:10.1056/NEJMoa2105000" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.284C>T,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 ('Kappa') reduced 3.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22317,22319,22320,23399,23401,23402,23403" "T95I,D253G,D253G,D253G,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "B.1.526 (Iota) substantially increased IFR in older adults: by 46% (95% CI: 7.4 – 84%) among 45-64 year-olds, 82% (95% CI: 20 – 140%) among 65-74 year-olds, and 62% (95% CI: 45 – 80%) among 75+ during Nov 2020 – Apr 2021, compared to baseline IFR estimated for preexisting variants. [minimum clade defining mutations listed]" "" "" "" "Yang" "2021" "https://doi.org/10.1101/2021.08.04.21261596" "doi:10.1101/2021.08.04.21261596" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Sera from vaccinees [ChAdOx1 and BNT162b2 primarily used in UK] shows decreased ability to neutralize B.1.621 compared to first wave virus and Alpha, with a magnitude of change similar to Beta." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against B.1.621." "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Sera from individuals who have been infected with Delta does not have strong neutralising activity against B.1.621" "" "" "" "" "2021" "https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 69 test-positive were Mu. Two dose vaccine efficacy against Mu was 90.4% (73.9-96.5%), one dose VE was 45.8% (0.0-88.9%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera." "" "" "" "Luftig" "2021" "https://doi.org/10.1056/NEJMc2104036" "doi:10.1056/NEJMc2104036" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using live B.1.621 virus and a cytopathic effect-based assay, sera from 37 Pfizer/BioNTech BNT162b2 vaccinees collected 10-20 days post-booster showed significantly lower (95) but still 'robust' neutralization than against ancestral B.1 virus (107)." "" "" "" "Messali" "2021" "https://doi.org/10.1002/jmv.27247" "doi:10.1002/jmv.27247" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 7.6x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. [This is a greater reduction than Beta @ 6.3x]" "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22597,22599,23012,23060,23061,23062,23063,23399,23401,23402,23403,23604,24410" "T95I,R346K,R346K,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H,D950N" "NC_045512.2:g.284C>T,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2848G>A" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 12.4x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. [This is a greater reduction than Beta @ 8.2x]" "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403" "T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 1.5x-fold lower (95% CI: 0.05x-0.07x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,22679,23039,23040,23521,23522,23524,23525,24130,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,23060,23061,23062,23063,22879,22881,22882,22882,21618,23071,23074,23075,22992,22995,23048,22810,22811,22812,22813,22813,22576,22577,22578,23604,22686,23053,23054,23055,22992,23009,23010,23012,23013,23399,23401,23402,23403" "T95I,S373P,Q493R,Q493R,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,T19R,Y505H,Y505H,Y505H,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,G339D,G339D,G339D,P681H,S375F,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.1117T>C,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2568C>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.56C>G,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1486G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1124C>T,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Thr19Arg,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 4.4-fold lower (95% CI: 4.3x-4.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,23012,23271,23399,23401,23402,23403,23604,23948" "T95I,E484K,A570D,D614G,D614G,D614G,D614G,P681H,D796H" "NC_045512.2:g.284C>T,NC_045512.2:g.1450G>A,NC_045512.2:g.1709C>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A,NC_045512.2:g.2386G>C" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp796His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "51yo female with no severe COVID-19 risk factors tested positive 19 days after second dose of mRNA-1273 (Moderna) vaccine. Presented with sore throat, congestion, and headache developed; the next day she lost her sense of smell. Symptoms resolved over a one week period. Serum obtained 4 days after symptom onset was tested for neutralization against wild-type virus, the E484K mutant, and the B.1.526 variant. It was equally effective against each. These data suggest that the antibody response recognized these variants but was nonetheless insufficient to prevent a breakthrough infection. The virus detected matched neither B.1.1.7 nor B.1.526 VOC strains in wide circulation in New York at the time of infection, though shared some mutations." "" "" "" "Hacisuleyman" "2021" "https://doi.org/10.1056/NEJMoa2105000" "doi:10.1056/NEJMoa2105000" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21846,23399,23401,23402,23403" "T95I,D614G,D614G,D614G,D614G" "NC_045512.2:g.284C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21855" "S98F" "NC_045512.2:g.293C>T" "YP_009724390.1:p.Ser98Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly enhanced the transduction rate in raccoon dog (Nyctereutes procyonoides) kidney (62.4%) and Rickett’s big-footed bat (Myotis pilosus) kidney (45.0%) cell cultures compared to epithelial-like human Huh-7 cells (38.9%)." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21929" "A123S" "NC_045512.2:g.367G>T" "YP_009724390.1:p.Ala123Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected in passage with mAb COV2-2489 during alanine mutagenesis antibody mapping experiment." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21969" "C136Y" "NC_045512.2:g.407G>A" "YP_009724390.1:p.Cys136Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massively decreases N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21969" "C136Y" "NC_045512.2:g.407G>A" "YP_009724390.1:p.Cys136Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "These variants dominate in mink infections in North America, sometime supplemented with F486L. The Y453F variant found in other jurisdictions in mink infections is notably absent in North America." "" "" "" "" "2021" "https://doi.org/10.1101/2021.03.18.21253734v3" "doi:10.1101/2021.03.18.21253734v3" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected twice in passage with mAb COV2-2489." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. [PG: This mutation is adjacent to a well known deletion, which may confound the significance of this variant]" "" "" "" "Lucaci" "2021" "https://observablehq.com/@aglucaci/sc2-omicron" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Average 2x neutralization efficiency decrease against sera from 26 Phase II trial Covaxin (BBV152) vaccine recipents. Very similar to B.1.1.7 (~2x) in the same study, and the neutralization from 17 sera of natural infections across B1 lineages." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.04.23.441101" "doi:10.1101/2021.04.23.441101" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~3.5x cleavage of S2 relative to WA1 (D614G) wildtype by Kappa (B.1.617.1) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~4.5x for closely related Delta B.1.617.2 also with P681R at the cleavage site)." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against B.1.617.1-v1 ('Kappa') reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617.1) showed a 1.79x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cluster of B.1.617[.1] infections related to travel from India to USA, one patient with mild symptoms had received their second dose of Pfizer vaccine more than two weeks before the infection [i.e. vaccine breakthrough]." "" "" "" "Verghese" "2021" "https://doi.org/10.1128/JCM.00741-21" "doi:10.1128/JCM.00741-21" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Kappa (B.1.617.1) shows mean 1.97x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.1) showed a 1.12x increase in binding (KD) relative to D614G, but described as 'not significant'. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Kappa (B.1.617.1) shows 5.71x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617.1) showed a 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Kappa (B.1.617.1) has an IC50 fold change of 80.2x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Kappa (B.1.617.1) has an IC50 fold change of 0.68x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Kappa (B.1.617.1) has an IC50 fold change of 2.3x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22022,22915,22916,22917,23012,23399,23401,23402,23403,23604,24775,21846" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R,Q1071H,T95I" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G,NC_045512.2:g.3213A>T,NC_045512.2:g.284C>T" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Kappa (B.1.617.1) has an IC50 fold change of 0.13x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 35B5. Omicron BA.2 has an IC50 fold change of 0.09x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "BnAb 002-S21F2 IC50 on the Omicron BA.2 variant is 0.8x fold the wildtype." "" "" "" "Kumar" "2022" "https://doi.org/10.1101/2022.05.13.491770" "doi:10.1101/2022.05.13.491770" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.2 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs 47D10. Omicron BA.2 has an IC50 fold change of 0.08x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.2 has an IC50 fold change of 0.07x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.2 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22992,22992,22995,23009,23010,23012,23013,23053,23054,23055,23060,23061,23062,23063,23071,23074,23075,23399,23401,23402,23403,23521,23522,23524,23525,23604" "G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,P681H" "NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.2 has an IC50 fold change of 0.04x." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21974" "D138Y" "NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.43 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21977" "P139S" "NC_045512.2:g.415C>T" "YP_009724390.1:p.Pro139Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected once in passage with mAb COV2-2676." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21981" "F140S" "NC_045512.2:g.419T>C" "YP_009724390.1:p.Phe140Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990" "Y145del,Y145del" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990" "Y145del,Y145del" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient." "" "" "" "McCarthy" "2021" "https://doi.org/10.1126/science.abf6950" "doi:10.1126/science.abf6950" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21987,21990,21993,21995,23012,23399,23401,23402,23403" "Y145del,Y145del,H146del,H146del,E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.436_438del,NC_045512.2:g.436_438del,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.His146del,YP_009724390.1:p.His146del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Normalized for particle number, on ACE2.293T cells showed that the B.1.618 spike protein was about as infective as D614G wild type." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21993,21995" "H146del,H146del" "NC_045512.2:g.436_438del,NC_045512.2:g.436_438del" "YP_009724390.1:p.His146del,YP_009724390.1:p.His146del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient." "" "" "" "McCarthy" "2021" "https://doi.org/10.1126/science.abf6950" "doi:10.1126/science.abf6950" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21997,21998,21999,22000,22001" "K147E,K147E,K147E,K147E,K147E" "NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G" "YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2X28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21997,21998,21999,22000,22001" "K147E,K147E,K147E,K147E,K147E" "NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G,NC_045512.2:g.439A>G" "YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "21998" "H146Y" "NC_045512.2:g.436C>T" "YP_009724390.1:p.His146Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in 4A8 monoclonal antibody EC50 (i.e. ablated recognition), but much milder effect on mAbs within antigenic supersite 'i'" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22001" "K147Q" "NC_045512.2:g.439A>C" "YP_009724390.1:p.Lys147Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22002" "K147T" "NC_045512.2:g.440A>C" "YP_009724390.1:p.Lys147Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X333" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22002" "K147T" "NC_045512.2:g.440A>C" "YP_009724390.1:p.Lys147Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massively decreases N terminal domain antigen recognition by supersite i mAbs S2M28, S2X28, S2X333, 4A8 (but not S2L28)." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22003" "K147N" "NC_045512.2:g.441A>T" "YP_009724390.1:p.Lys147Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22005" "N148S" "NC_045512.2:g.443A>G" "YP_009724390.1:p.Asn148Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong positive selection (up to 72% of supernatant sequences) under six rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22010" "K150E" "NC_045512.2:g.448A>G" "YP_009724390.1:p.Lys150Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22010" "K150E" "NC_045512.2:g.448A>G" "YP_009724390.1:p.Lys150Glu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong positive selection (up to 40% of supernatant sequences) under three rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22011" "K150T" "NC_045512.2:g.449A>C" "YP_009724390.1:p.Lys150Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 22% of supernatant sequences) after COV47 convalescent plasma assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22011" "K150R" "NC_045512.2:g.449A>G" "YP_009724390.1:p.Lys150Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 18% of supernatant sequences) under two rounds of COV47 convalescent plasma passage" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22016,22016" "W152R,W152R" "NC_045512.2:g.454T>A,NC_045512.2:g.454T>C" "YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22016,22016" "W152R,W152R" "NC_045512.2:g.454T>A,NC_045512.2:g.454T>C" "YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For NTD-binding neutralizing antibody ADI-56479 this mutation causes a 1000x drop in neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22018" "W152C" "NC_045512.2:g.456G>T" "YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "The W152C mutation reduced recognition of six NTD neutralizing mAbs, including a complete loss of binding for two of them, with a complementary pattern to that observed for S13I (also found in lineage B.1.427/B.1.429) out of 11 neutralizing mAbs evaluated." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22018" "W152C" "NC_045512.2:g.456G>T" "YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Pseudoviruses carrying the W152C mutation demonstrated small increases in cell entry compared to D614G alone in 293T cells and human airway organoids." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022" "E154K" "NC_045512.2:g.460G>A" "YP_009724390.1:p.Glu154Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 15 Pfizer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~3x (compared to ~11x for B.1.351). [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abrogates Bamlanivimab neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Significant decrease in combined Etesevimab+Bamlanivimab neutralization except at the highest concentration measured. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In two of eight cell lines tested (Caco-2 intenstinal and Calu-3 lung), a modest increase in cell entry was observed. This increase was not observed in a Calu-3 cell line with overexpressed ACE2. [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22022,22915,22916,22917,23012,23399,23401,23402,23403,23604" "E154K,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,P681R" "NC_045512.2:g.460G>A,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Approximately 2-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally]" "" "" "" "Hoffman" "2021" "https://doi.org/10.1101/2021.05.04.442663" "doi:10.1101/2021.05.04.442663" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22028,22034" "R158G,R158G" "NC_045512.2:g.467_472del,NC_045512.2:g.472A>G" "YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22033,23012,23604" "F157L,E484K,P681R" "NC_045512.2:g.471C>A,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.23.1-v2 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22033,23604" "F157L,P681R" "NC_045512.2:g.471C>A,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralization efficiency (ID50) against A.23.1-v1 reduced 1.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster." "" "" "" "Choi" "2021" "https://doi.org/10.1101/2021.06.28.449914" "doi:10.1101/2021.06.28.449914" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22036" "R158S" "NC_045512.2:g.474A>T" "YP_009724390.1:p.Arg158Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Selected three times in passage with mAb COV2-2489." "" "" "" "Suryadevara" "2021" "https://doi.org/10.1101/2021.01.19.427324" "doi:10.1101/2021.01.19.427324" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*16:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*07:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DPB1*04:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:03." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22093,22093,22093" "M177I,M177I,M177I" "NC_045512.2:g.531G>A,NC_045512.2:g.531G>T,NC_045512.2:g.531G>C" "YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type C*07:02." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22107,22111" "Q183H,Q183H" "NC_045512.2:g.549G>T,NC_045512.2:g.549G>T" "YP_009724390.1:p.Gln183His,YP_009724390.1:p.Gln183His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome" "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132" "R190S" "NC_045512.2:g.570G>T" "YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.69 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604" "R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in B.1.640.2 variant was ~1000x folds more significant in 8 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22132,22600,22600,22907,23060,23061,23062,23063,23399,23401,23402,23403,23604" "R190S,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.570G>T,NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C,NC_045512.2:g.1345T>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1.640.2 variant was ~5.6x folds more significant in 9 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22188,23399,23401,23402,23403" "I210del,D614G,D614G,D614G,D614G" "NC_045512.2:g.629_631del,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "A 42yo Iranian male was reinfected with B.1.36 lineage virus 128 days after infection with genetically distinct B.1.36 virus, with negative PCR tests in between. In the first instance patient presented with cough, headache, severe diarrhea. In the second instance symptoms were more severe: body pain, shortness of breath, headache and anosmia. Anti-SARS-CoV-2 IgG and IgM tests were negative after both episodes. [Non-seroconversion may be associated with elevated risk of re-infection] [I210del is a homoplasy that has appeared in several disparate parts of the global phylogenetic tree, including A and B lineages, primarily in LMICs]" "" "" "" "Salehi-Vaziri" "2021" "https://doi.org/10.1016/j.virusres.2021.198421" "doi:10.1016/j.virusres.2021.198421" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.98 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*13:02." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:01." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:02." "" "" "" "Riou" "2021" "https://doi.org/10.1126/scitranslmed.abj6824" "doi:10.1126/scitranslmed.abj6824" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22206" "D215G" "NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227" "A222V,A222V" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite 'i' monoclonal antibodies." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227,23399,23401,23402,23403" "A222V,A222V,D614G,D614G,D614G,D614G" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3). Both cases were mild. Second case also includes N:p.A220V" "" "" "" "Brehm" "2021" "https://doi.org/10.3390/v13040661" "doi:10.3390/v13040661" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22224,22227,23399,23401,23402,23403" "A222V,A222V,D614G,D614G,D614G,D614G" "NC_045512.2:g.665C>T,NC_045512.2:g.665C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "humoral response durability" "" "" "27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3), i.e. with a 9 month interval. Both cases were mild. No significant differences in the neutralizing capacity of the two lineages were observed in 4 sera taken (1 pre-reinfection, three post-reinfection). Neutralizing antibody titres (IC50) before and immediately after re-infection were <300 against both strains, and jumped >7x upon re-infection. Viral titres were also higher in the second case. Second case also includes N:p.A220V" "" "" "" "Brehm" "2021" "https://doi.org/10.3390/v13040661" "doi:10.3390/v13040661" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22293" "L244S" "NC_045512.2:g.731T>C" "YP_009724390.1:p.Leu244Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22301" "S247R" "NC_045512.2:g.739A>C" "YP_009724390.1:p.Ser247Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22304" "Y248H" "NC_045512.2:g.742T>C" "YP_009724390.1:p.Tyr248His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22314" "P251L" "NC_045512.2:g.752C>T" "YP_009724390.1:p.Pro251Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317" "G252D" "NC_045512.2:g.755G>A" "YP_009724390.1:p.Gly252Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317,22319,22320" "D253G,D253G,D253G" "NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22317,22319,22320" "D253G,D253G,D253G" "NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite 'i', but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22319" "D253Y" "NC_045512.2:g.757G>T" "YP_009724390.1:p.Asp253Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite 'i', but no effect on other mAbs within that supersite" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22323" "S254F" "NC_045512.2:g.761C>T" "YP_009724390.1:p.Ser254Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not associated with significant reduction of EC50 (recognition) in any antigenic supersite 'i' monoclonal antibodies." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22323" "S254Y" "NC_045512.2:g.761C>A" "YP_009724390.1:p.Ser254Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22326" "S255F" "NC_045512.2:g.764C>T" "YP_009724390.1:p.Ser255Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22328,22329,22331" "G257S,G257S,G257S" "NC_045512.2:g.769G>A,NC_045512.2:g.769G>A,NC_045512.2:g.769G>A" "YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334" "W258R" "NC_045512.2:g.772T>C" "YP_009724390.1:p.Trp258Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334" "W258R" "NC_045512.2:g.772T>C" "YP_009724390.1:p.Trp258Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28" "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.01.14.426475" "doi:10.1101/2021.01.14.426475" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22334,22879,22881,22882,22882,22904,22910,23012" "W258R,N440K,N440K,N440K,N440K,N450D,N450D,E484K" "NC_045512.2:g.772T>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22340" "A260T" "NC_045512.2:g.778G>A" "YP_009724390.1:p.Ala260Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22344" "G261D" "NC_045512.2:g.782G>A" "YP_009724390.1:p.Gly261Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Multiple mink but no humans on one farm in Denmark, potential adaptation." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22377" "P272L" "NC_045512.2:g.815C>T" "YP_009724390.1:p.Pro272Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*02:01." "" "" "" "Dolton" "2021" "https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf" "doi:10.1101/2021.06.21.21259010v2.full.pdf" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22377" "P272L" "NC_045512.2:g.815C>T" "YP_009724390.1:p.Pro272Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*08:01." "" "" "" "Dolton" "2021" "https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf" "doi:10.1101/2021.06.21.21259010v2.full.pdf" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 1.2x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.3 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22576,22577,22578" "G339D,G339D,G339D" "NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A" "YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22583" "V341I" "NC_045512.2:g.1021G>A" "YP_009724390.1:p.Val341Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22599" "R346T,R346T,R346T,R346T" "NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22599" "R346T,R346T,R346T,R346T" "NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22595,22596,22597,22599,22679,22686,22783,22784,22785,22786,22786,22810,22811,22812,22813,22813,22879,22881,22882,22882,22939,22942,22942,22992,23009,23010,23012,23013,23027,23029,23030,23031,23053,23054,23055,22992,22995,23060,23061,23062,23063,23071,23074,23075" "R346T,R346T,R346T,R346T,S373P,S375F,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N460K,N460K,N460K,S477N,E484A,E484A,E484A,E484A,F490S,F490S,F490S,F490S,Q498R,Q498R,Q498R,T478K,T478K,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H" "NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1037G>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A,NC_045512.2:g.1430G>A,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The hACE2-binding affinity of XBB.1.5 RBD has a dissociation constant KD of 3.4 nM, where S486P is the distinguishing Spike mutation vs parent XBB.1 RBD with a much weaker KD (19 nM), as measured by surface plasmon resonance (SPR) assays." "" "" "" "Yue" "2023" "https://doi.org/10.1101/2023.01.03.522427" "doi:10.1101/2023.01.03.522427" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346K,R346K" "NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 53% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346K,R346K" "NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation, which has emerged in some Omicron sequences, has a 0.7x reduction in neutralization activity with Sotrovimab in a VSV model on Vero E6 cells. [Omicron sequences with R346K may very well have a non-additive neutralization rather than 2.7x+0.7x = 3.4x]" "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346K,R346K" "NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22597,22599" "R346I,R346I" "NC_045512.2:g.1037G>T,NC_045512.2:g.1037G>T" "YP_009724390.1:p.Arg346Ile,YP_009724390.1:p.Arg346Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Provides ~80% escape from mAb COV2-2130, even though its appearance in culture is formed without selective mAb pressure." "" "" "" "Dong" "2021" "https://doi.org/10.1101/2021.01.27.428529" "doi:10.1101/2021.01.27.428529" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 2/3 antibody C603." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22600,22600" "R346S,R346S" "NC_045512.2:g.1038A>T,NC_045512.2:g.1038A>C" "YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 30% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22622" "N354D" "NC_045512.2:g.1060A>G" "YP_009724390.1:p.Asn354Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.13 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22624" "N354K" "NC_045512.2:g.1062C>A" "YP_009724390.1:p.Asn354Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22627,22629" "K356T,K356T" "NC_045512.2:g.1067A>C,NC_045512.2:g.1067A>C" "YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.14 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22629" "K356R" "NC_045512.2:g.1067A>G" "YP_009724390.1:p.Lys356Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22632" "R357K" "NC_045512.2:g.1070G>A" "YP_009724390.1:p.Arg357Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.18 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.72 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22634" "I358F" "NC_045512.2:g.1072A>T" "YP_009724390.1:p.Ile358Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as 'stabilizing' since it nicely fitsinside the hydrophobic pocket formed in the RBD domain." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22661" "V367I" "NC_045512.2:g.1099G>A" "YP_009724390.1:p.Val367Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22679" "S373P" "NC_045512.2:g.1117T>C" "YP_009724390.1:p.Ser373Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Reduce affinity for mildly cross-reactive CR3022 (2003 pandemic SARS monoclonal antibody cross-reactive to SARS-CoV-2)" "" "" "" "Long" "2020" "https://doi.org/10.1128/mBio.02707-20" "doi:10.1128/mBio.02707-20" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22679,23009,23010,23012,23013" "S373P,E484A,E484A,E484A,E484A" "NC_045512.2:g.1117T>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "On December 7, 2021 the estimate of Omicron effective reproduction rate (Rt) is 3.12 [presumably R0 is higher], compared to 1.12 for the dominant Delta VOC at that time. [shorthand of variant list shraed by all contemporary BA lineage used here]" "" "" "" "" "2021" "https://doi.org/10.47326/ocsat.dashboard.2021.1.0" "doi:10.47326/ocsat.dashboard.2021.1.0" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22686" "S375F" "NC_045512.2:g.1124C>T" "YP_009724390.1:p.Ser375Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch." "" "" "" "Lucaci" "2021" "https://observablehq.com/@aglucaci/sc2-omicron" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22696" "K378N" "NC_045512.2:g.1134G>T" "YP_009724390.1:p.Lys378Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for mildly neutralizing COV2-2677 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23402,23403" "P384L,D614G,D614G,D614G,D614G" "NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23402,23403" "P384L,D614G,D614G,D614G,D614G" "NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22713,23399,23401,23402,23403" "P384L,D614G,D614G,D614G,D614G" "NC_045512.2:g.1151C>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22745" "V395I" "NC_045512.2:g.1183G>A" "YP_009724390.1:p.Val395Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22766" "I402V" "NC_045512.2:g.1204A>G" "YP_009724390.1:p.Ile402Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22783,22784,22785,22786,22786" "R408S,R408S,R408S,R408S,R408S" "NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C" "YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22783,22784,22785,22786,22786,23009,23010,23012,23013,23060,23061,23062,23063" "R408S,R408S,R408S,R408S,R408S,E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a study of 481 vaccinees going from lowest to highest infection rate, 2 doses of CoronaVac and 1 dose of BNT162b2 had the lowest infection rate at 6.3%, then it was 3 doses of BNT162b2 having a infection rate of 16.6%. 2 and 3 doses of CoronaVac had 48.6% and 20.6% infection rate respectively. 2 doses of BNT162b2 has the highest infection rate at 49.2%." "" "" "" "Zhou" "2022" "https://doi.org/10.1101/2022.05.09.491254" "doi:10.1101/2022.05.09.491254" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 36.9 fold decrease in KD value for antibody binding of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 1.5 fold decrease in KD value of antibody binding of ACE2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection, Two-tailed Wilcoxon matched-pairs signed-rank test shows mild resistance P=0.0361." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs)" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 7.5 fold decrease in KD value for antibody binding of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "1.1 fold drop in IC50 of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.86 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C682, and to a lesser extent C614 and C660" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~6x binding against this isolated mutation. Estesevimab lost ~100x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates binding by RBD-directed mAbs CB6 and 910-30 (targeting the inner side of the RBD). Pseudotyped virus model impairs binding by RBD-directed mAbs 4-20 and REGN10933." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 3-fold decrease in affinity compared to wild-type RBD on the cell surface (Kd = 145.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against IgG1 monoclonal antibody ab1." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The K417N mutation decreased the affinity ~4 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813" "K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This combination showed ~3x increase binding to ACE2 vs wild type, about half that of the B.1.1.7 lineage, suggesting that the K417N mutation is slightly detrimental to ACE2 binding, probably as a result of disrupting the salt bridge formed with ACE2 residue D30" "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y." "" "" "" "Laffeber" "2021" "https://doi.org/10.1101/2021.02.22.432357" "doi:10.1101/2021.02.22.432357" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant." "" "" "" "Vogel" "2021" "https://doi.org/10.1101/2021.03.04.433887" "doi:10.1101/2021.03.04.433887" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of the B.1.351 RBD variants for ACE2 increased by 3.7 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from B.1.351." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 ('South African') lineage background" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.16.431305" "doi:10.1101/2021.02.16.431305" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "B.1.351 and P.1 samples showed average Ct cycle threshold of 22.2 vs 23 for wildtype (i.e. ~60% higher viral load) comparing 3360 and 22535 samples respectively." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.03.19.21253971" "doi:10.1101/2021.03.19.21253971" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In Moderna vaccinee sera, 2.7x reduction in neutralization, and 6.4 for the full B.1.351 Spike mutation complement, but despite the observed decreases, titers in human vaccinee sera against the B.1.351 variant remained at clinically significant level of ~1/300." "" "" "" "Wu" "2021" "https://doi.org/10.1101/2021.01.25.427948" "doi:10.1101/2021.01.25.427948" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26)." "" "" "" "Teyssou" "2021" "https://doi.org/10.1101/2021.03.21.21253498" "doi:10.1101/2021.03.21.21253498" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.4-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.351 key variants lentivirus. Compare to 8.8-fold reduction against cultured B.1.351 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibodies ab8 and IgG1 ab1. Complete loss for the same antibodies was also observed against S1 pseudotyped and full Spike protein trimers with both B.1.351 and P.1 lineage variants, with slight binding signal for P.1 against IgG1 at the highest concentration tested (1uM). Complete loss of neutralization by these two antibodies was also observed." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "27% of 44 early pandemic exposure convalescent plasma/sera lose all activity against a RBD triple mutant pseudovirus (RBD mutatants of the 501Y.V2 'South African' lineage), while only 23% retained high titres" "" "" "" "Wibmer" "2021" "https://doi.org/10.1101/2021.01.18.427166" "doi:10.1101/2021.01.18.427166" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure." "" "" "" "Pearson" "2021" "https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) with enrollment June 24 and November 9, 2020 from ~2000 HIV-negative 18-64 year olds (1:1 placebo to treatment), incidence of serious adverse events 14 or more days post- 2nd dose was balanced between the vaccine and placebo groups. A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed 3.5x reduction in neutralization (ID50) for B.1.351 RBD pseudotype HIB-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a similar 3.2x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera)." "" "" "" "Madhi" "2021" "https://doi.org/10.1056/NEJMoa2102214" "doi:10.1056/NEJMoa2102214" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolished neutralization by mAbs CQ026 and CQ038, greatly diminished neutralization by CQ012 and CQ046." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China)." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Average ~10-fold reduction in neutralization efficacy in convalescent sera of 16 health workers infected in Spring 2020." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 2 (B.1.351) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2." "" "" "" "Hu" "2021" "https://doi.org/10.1101/2021.01.22.427749" "doi:10.1101/2021.01.22.427749" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "36,590 variant-specific RT-PCR tests were performed on samples collected between April 12 and May 7, 2021 in France to compare variant spread. Compared to January to March 2021, B.1.351 variant had a significant transmission advantage over B.1.1.7 in some regions (15.1 to 16.1% in Île-de-France and 16.1 to 18.8% in Hauts-de-France). This shift in transmission advantage is consistent with the immune evasion abilities of B.1.351 and the high levels of immunization in these regions." "" "" "" "Roquebert" "2021" "https://doi.org/10.1101/2021.05.12.21257130" "doi:10.1101/2021.05.12.21257130" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant of key B.1.351 lineage mutations showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23012,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23041,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "100% of the 5 8‑month‑old male R3P1-E4 antibody treated mice suvived 14 days after infection while only 60% the control group mice survived 5 days post infection." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23041,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trachea viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~750x fold drop in the R3P1-E4 antibody in comparison to the IgG control." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23041,23060,23061,23062,23063" "K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1479A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Lung viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~2266x fold drop in the R3P1-E4 antibody in comparison to the IgG control." "" "" "" "Li" "2022" "https://doi.org/10.1186/s13578-022-00794-7" "doi:10.1186/s13578-022-00794-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (no synergy as level approx. that of N501Y alone)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~5x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied]" "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22810,22811,22812,22813,22813,23399,23401,23402,23403" "K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.64 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 antibody C682" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The K417T mutation decreased the affinity ~2 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~16x binding against this isolated mutation. Estesevimab lost ~16x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "No detectable fold drop in IC50 of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P22A-1D1." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 1.1 fold decrease in KD value of antibody binding of ACE2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.25 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 2.9 fold decrease in KD value for antibody binding of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes no detectable change in KD value for antibody binding of P5A-1D2." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Causes 57.1 fold decrease in KD value for antibody binding of P5A-3C8." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812" "K417T" "NC_045512.2:g.1250A>C" "YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "2.6 fold increase in IC50 of P2C-1F11." "" "" "" "Zhang" "2021" "https://doi.org/10.1038/s41467-021-24514-w" "doi:10.1038/s41467-021-24514-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,23012,23060,23061,23062,23063" "K417T,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from P.1." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,23012,23060,23061,23062,23063" "K417T,E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The affinity of the P.1 RBD variants for ACE2 increased by 5.3 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22812,23012,23060,23061,23062,23063,23399,23401,23402,23403" "K417T,E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The KD for the pseudotyped P.1-ACE2 interaction is 4.8 nM, showing that binding to P.1 is essentially indistinguishable from B.1.351 (4.0 nM), which binds with ~19x greater affinity that wild type." "" "" "" "Dejnirattisai" "2021" "https://doi.org/10.1016/j.cell.2021.03.055" "doi:10.1016/j.cell.2021.03.055" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22820" "D420N" "NC_045512.2:g.1258G>A" "YP_009724390.1:p.Asp420Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22851" "T430I" "NC_045512.2:g.1289C>T" "YP_009724390.1:p.Thr430Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22865" "A435S" "NC_045512.2:g.1303G>T" "YP_009724390.1:p.Ala435Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb H014 (on D614G background)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 3 antibody C669 mildly selected for the emergence of the N440K mutation in vitro (in contrast to N440H which caused mild escape in Class 1/2 mAb C653)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The N440K variant produced ten times higher infectious viral titers than a prevalent A2a strain, and over 1000 folds higher titers than a much less prevalent A3i strain prototype in Caco2 cells. Interestingly, A3i strain showed the highest viral RNA levels, but the lowest infectious titers in the culture supernatants, indicating the absence of correlation between the RNA content and the infectivity of the sample." "" "" "" "Tandel" "2021" "https://doi.org/10.1101/2021.04.30.441434" "doi:10.1101/2021.04.30.441434" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 45% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, eliminated in subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 0.7x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "N501Y substitution decreased the neutralizing and binding activities of CB6 and increased that of BD-23" "" "" "" "Cheng" "2021" "https://doi.org/10.1186/s12985-021-01554-8" "doi:10.1186/s12985-021-01554-8" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882" "N440K,N440K,N440K,N440K" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22879,22881,22882,22882,23399,23401,23402,23403" "N440K,N440K,N440K,N440K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "A 47yo Indian male was reinfected with B.1.36 lineage virus in September 2020 after infection with genetically distinct B.1.36 virus in July, with negative PCR tests in between. While the forst episode was asymptomatic, the second included fever, cough, and malaise. The second case additionally contained stopgain ORF3a:E261*" "" "" "" "Rani" "2021" "https://doi.org/10.1002/jmv.26997" "doi:10.1002/jmv.26997" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444R" "NC_045512.2:g.1331A>G" "YP_009724390.1:p.Lys444Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Identified in 6/20 replicates of recombinant VSV growth in the presence of mAb COV2-2130." "" "" "" "Dong" "2021" "https://doi.org/10.1101/2021.01.27.428529" "doi:10.1101/2021.01.27.428529" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444R" "NC_045512.2:g.1331A>G" "YP_009724390.1:p.Lys444Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 20% of supernatant sequences) under two rounds of COV-NY convalescent plasma passage, eliminated in rounds three and four" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444T" "NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444T" "NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22893" "K444T" "NC_045512.2:g.1331A>C" "YP_009724390.1:p.Lys444Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Results in 3.7-fold drop in neutralization potency for COVA2-29, which is a cluster I RBD141 specific antibody." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Positive selection (up to 14% of supernatant sequences) after COV-NY convalescent plasma assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-01 and moderately resistant to 2H04 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Abolishes binding efficiency vs wild type for mAb REGN10933." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22894,22894" "K444N,K444N" "NC_045512.2:g.1332G>C,NC_045512.2:g.1332G>T" "YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Improvement in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22896" "V445A" "NC_045512.2:g.1334T>C" "YP_009724390.1:p.Val445Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 41% appearance in 2 passages against Regeneron monoclonal antibody RGN10987 @ 10ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Decrease in neutralization capability of all 4 convalescent sera tested (1 ablated)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 1 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-02, SARS2-32 and SARS2-35 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2499 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22899" "G446D" "NC_045512.2:g.1337G>A" "YP_009724390.1:p.Gly446Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed a ~4x drop in sensitivity." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 95% appearance in 2 passages against Regeneron monoclonal antibody RGN10934 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-07 nd moderately resistant to SARS2-16 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 4 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450D,N450D" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Most effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910" "N450Y,N450Y" "NC_045512.2:g.1348A>T,NC_045512.2:g.1348A>T" "YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations), triple replicates. Against a broader panel of 16 convalescent plasma (no replicates), reductions in neutralization are considerably less dramatic in pattern, and sometime neutralization increases." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22904,22910,23012,23039,23040,23373,25046" "N450D,N450D,E484K,Q493R,Q493R,T604I,P1162S" "NC_045512.2:g.1348A>G,NC_045512.2:g.1348A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1811C>T,NC_045512.2:g.3484C>T" "YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Thr604Ile,YP_009724390.1:p.Pro1162Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22905" "N448S" "NC_045512.2:g.1343A>G" "YP_009724390.1:p.Asn448Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22907" "Y449N" "NC_045512.2:g.1345T>A" "YP_009724390.1:p.Tyr449Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22907" "Y449H" "NC_045512.2:g.1345T>C" "YP_009724390.1:p.Tyr449His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912" "N450K" "NC_045512.2:g.1350T>G" "YP_009724390.1:p.Asn450Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912,22916" "L452M,L452M" "NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A" "YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22912,22916" "L452M,L452M" "NC_045512.2:g.1354C>A,NC_045512.2:g.1354C>A" "YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-02 and SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We observed increased entry by pseudoviruses carrying the L452R mutation compared to D614G alone, with a 6.7 to 22.5-fold increase in 293T cells and a 5.8 to 14.7-fold increase in human airway organoids." "" "" "" "Deng" "2021" "https://doi.org/10.1101/2021.03.07.21252647" "doi:10.1101/2021.03.07.21252647" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.32 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~1.7-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Increased stability of RBD expression in yeast, suggesting increased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. L452R conferred about a two-fold reduction in neutralisation by vaccine sera, but was not statistically significant with this sample size." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "L452R derivative virus did not induce IFN-gamma expression even at the highest concentration tested (10 nM) in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456)." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs X593 and P2B-2F6" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. [listed as L454R in Figure, but L452R in text, also text suggests not statistically significant, but error bars say otherwise in Figure 4]" "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "10 of 14 RBD-specific mAbs that showed at least 10-fold reduced neutralization of B.1.427/B.1.429 variant pseudotype (S13I, W152C, and L452R) were also found to poorly bind to just a L452R RBD mutant, demonstrating a role for this mutation as an escape mechanism for certain RBD-targeting mAbs." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02." "" "" "" "Motozono" "2021" "https://doi.org/10.1016/j.chom.2021.06.006" "doi:10.1016/j.chom.2021.06.006" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2/3 antibody C628 and class 2 antibody C643 selected for the emergence of the L452R mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.67 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency." "" "" "" "McCallum" "2021" "https://doi.org/10.1101/2021.03.31.437925" "doi:10.1101/2021.03.31.437925" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Ablation of neutralization capability of 3 of 4 convalescent sera tested, the other is significantly hindered." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Observed ~2x decrease on average in neutralization efficacy in convalescent sera of 16 health workers." "" "" "" "Alenquer" "2021" "https://doi.org/10.1101/2021.04.22.441007" "doi:10.1101/2021.04.22.441007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 3 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~5x binding against this isolated mutation. Cligavimab lost ~4x binding against this isolated mutation. Regdanvimab lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917" "L452R,L452R,L452R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012" "L452R,L452R,L452R,E484Q" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484Q had a ~5x drop in neutralization (vs ~10x for E484K). When E484Q and L452R were combined, the fold change was significant, but similar to that of L452R alone (~2x), suggesting no evidence for an additive effect [perhaps even E484Q effect dilution]." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012" "L452R,L452R,L452R,E484K" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant combination shows a ~4-5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, same as L452R alone." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x infectivity advantage to the spike particles [less than L452R or E484Q alone working with the delins]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.4x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees)" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The combination caused a 3-fold increase in infectivity relative to D614G wild type. [compare to 3.5x for L452R alone]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2.5x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.617) showed a 1.30x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.18x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Pseudotyped viruses for B.1.617 was 2.3-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. [details on the convalescent patient sera collection are not abundantly clear in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x drop in neutralization (NT50) [working with the delins, less than just L452R but more than just E484Q]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617) showed a 1.85x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.617) showed a 1.22x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred fro common knowledge]" "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604" "L452R,L452R,L452R,E484Q,P681R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "In 9 infected hamsters each for B.1 and B.1.617.1, no significant change in viral load or subgenomic RNA levels were detected." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.05.05.442760" "doi:10.1101/2021.05.05.442760" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604" "L452R,L452R,L452R,E484K,P681R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant combination shows a ~3x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, significantly less of a decrease than any B.1.617 lineage variants alone, suggesting a synergistic effect on cell entry while maintaining known immunity esacpe mutants." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604" "L452R,L452R,L452R,E484Q,P681R" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Gross examination of 3+3 hamster lung specimens showed pronounced congestion and hemorrhages on days 5 and 7 post-infection in the case of the B.1.617.1 as compared with the B.1. The lung lesions with the B.1 variant were minimal to mild whereas with B.1.617.1 they were moderate. For B.1 pneumonic changes were minimal to mild (inflammatory cell infiltration, focal consolidation and mild congestion). The pronounced changes (moderate to severe) with mononuclear infiltration in the alveolar interstitial space, interstitial septal thickening, consolidation and pneumocyte hyperplasia were observed with B.1.617.1 variant consistently." "" "" "" "Yadav" "2021" "https://doi.org/10.1101/2021.05.05.442760" "doi:10.1101/2021.05.05.442760" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23012,23604,23399,23401,23402,23403" "L452R,L452R,L452R,E484Q,P681R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1450G>C,NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Normalized for particle number, on ACE2.293T cells showed that the B.1.617 spike protein was >2-fold increase in infectivity relative to D614G wild type." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23060,23061,23062,23063" "L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of these B.1.417/B.1.429 defining variants in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 583 test-positive were Epsilon. Two dose vaccine efficacy against Epsilon was 97.6 (90.2-99.4%), one dose VE was 76.3 (48.1-89.1%)." "" "" "" "Bruxvoort" "2021" "https://doi.org/10.1101/2021.09.29.21264199" "doi:10.1101/2021.09.29.21264199" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 7.42x drop in neutralization (NT50) [mostly from 3 of the sera]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "The L452R mutation increased the infectivity more than two-fold in these conditions." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this RBD mutation conferred a 2.36x drop in neutralization (NT50)." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2x." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~2x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22915,22916,22917,23399,23401,23402,23403" "L452R,L452R,L452R,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917" "L452Q" "NC_045512.2:g.1355T>A" "YP_009724390.1:p.Leu452Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917" "L452Q" "NC_045512.2:g.1355T>A" "YP_009724390.1:p.Leu452Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.27 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Mean 1.7x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.048x fold change in IC50 in C.37 Lambda" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mean 3.4x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset." "" "" "" "Uriu" "2021" "https://doi.org/10.1101/2021.09.06.459005" "doi:10.1101/2021.09.06.459005" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22917,23027,23029,23030,23031,23399,23401,23402,23403" "L452Q,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G" "NC_045512.2:g.1355T>A,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.038x fold change in IC50 in C.37 Lambda" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.25 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "VSV pseudotyped with Y453F reduced inhibition by most of the 13 potent convalescent serum/plasma samples tested, albeit with variable efficiency (median increase of serum/plasma titer required for 50% neutralization [NT50] = 1.62x, range = 1.02x to 3.43x), indicating that this RBD mutation may compromise SARS-CoV-2 control by preexisting neutralizing antibody responses." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.celrep.2021.109017" "doi:10.1016/j.celrep.2021.109017" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "10-fold reduction in binding efficiency vs wild type for MAb REGN10933." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Casirivimab lost >50x binding against this mutation." "" "" "" "Hoffman" "2021" "https://doi.org/10.1016/j.celrep.2021.109017" "doi:10.1016/j.celrep.2021.109017" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02." "" "" "" "Motozono" "2021" "https://doi.org/10.1016/j.chom.2021.06.006" "doi:10.1016/j.chom.2021.06.006" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "" "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "The induction level of IFN-gamma expression by the Y453F derivative in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456) was significantly lower." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~12x binding against this double mutation. Casirivimab lost ~64x binding against this double mutation. Cligavimab lost ~6x binding against this double mutation. Estesevimab lost ~10x binding against this double mutation. Imdevimab lost ~5x binding against this double mutation. Regdanvimab lost ~8x binding against this double mutation. Sotrovimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed in 4 separate mink farms in Denmark, and Y453F is circulating relatively widely in humans." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920" "Y453F" "NC_045512.2:g.1358A>T" "YP_009724390.1:p.Tyr453Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22920,21762,21763,21764,21765,21766,21766,21761" "Y453F,H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.1358A>T,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "The so-called 'delta F' variant combination previously observed in mink spillover events also emerged in a lymphoma patient (non-Hodgkin diffuse B-cell lymphoma IV stage B) with a long-term COVID-19 infection (4 months) where 18 de novo mutation occureed overall. Patient was taking rituximab, the B-cell-depleting agent, and had no detectable neutralizing antibody response." "" "" "" "Bazykin" "2021" "https://virological.org/t/emergence-of-y453f-and-69-70hv-mutations-in-a-lymphoma-patient-with-long-term-covid-19/580" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22924,22925,22926" "L455S,L455S,L455S" "NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C,NC_045512.2:g.1364T>C" "YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser,YP_009724390.1:p.Leu455Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.45 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22926,22927,22927,22928,22930,22930" "F456L,F456L,F456L,F456L,F456L,F456L" "NC_045512.2:g.1366T>C,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>A,NC_045512.2:g.1366T>C,NC_045512.2:g.1368T>G,NC_045512.2:g.1368T>A" "YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This double substitution reduces neutralization by RBD-specific mAbs from different clusters, specifically, the cluster I mAb COVA2-29, cluster III mAb COVA2-07 and cluster VI mAb COVA1-12. For COVA1-12 all neutralization activity is abolished, while COVA2-07 activity is just below the level required to calculate an IC50 value." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22928" "F456V" "NC_045512.2:g.1366T>G" "YP_009724390.1:p.Phe456Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Moderate in vitro selection against class 1 (Spike 'up' conformation) antibodies C683 and C664. Unclassified antibody C666 selected for the emergence of the F456V mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22936" "K458N" "NC_045512.2:g.1374G>T" "YP_009724390.1:p.Lys458Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22939,22942,22942" "N460K,N460K,N460K" "NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>G,NC_045512.2:g.1380T>A" "YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.09 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mild escape mutant emergent for class 1 antibody C613 in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460Y" "NC_045512.2:g.1378A>T" "YP_009724390.1:p.Asn460Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22940" "N460H" "NC_045512.2:g.1378A>C" "YP_009724390.1:p.Asn460His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22941" "N460I" "NC_045512.2:g.1379A>T" "YP_009724390.1:p.Asn460Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22941" "N460S" "NC_045512.2:g.1379A>G" "YP_009724390.1:p.Asn460Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22964" "I468V" "NC_045512.2:g.1402A>G" "YP_009724390.1:p.Ile468Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22964" "I468V" "NC_045512.2:g.1402A>G" "YP_009724390.1:p.Ile468Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22976" "I472V" "NC_045512.2:g.1414A>G" "YP_009724390.1:p.Ile472Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22976" "I472V" "NC_045512.2:g.1414A>G" "YP_009724390.1:p.Ile472Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb X593 (on D614G background)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~50x binding against this isolated mutation. Estesevimab lost ~8x binding against this isolated mutation. Sotrovimab lost ~30x binding against this isolated mutation. Tixagevimab lost ~15x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some class 1 (Spike 'up' conformation) antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22986" "A475V" "NC_045512.2:g.1424C>T" "YP_009724390.1:p.Ala475Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C102, C105 and C144 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 11 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.22 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding, with increasing proportion in subsequent rounds." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility." "" "" "" "Singh" "2021" "https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows some resistence across all antibodies tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 2 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of mild positive and negative changes in neutralization capability of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), 10 show low neutralization." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "While S477N itself is highly resistent to a broad range of monoclonal antibodies, combined with S514F high neutralization is restricted to only three antibodies in a broad screen." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-07, SARS2-16 and SARS2-19 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 host variant dependency" "" "" "This mutation's measured interaction affinity with ACE2:p.S19P (0.03% minor allele frequency, found almost exclusively in African/African-Americans in the GnomAD database) was significantly lower than the predicted value, indicating that these mutations were not independent. This is consistent with the fact that the ACE2 residue S19 is adjacent to RBD residue S477 in the contact interface." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-07 and SARS2-16 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992" "S477N" "NC_045512.2:g.1430G>A" "YP_009724390.1:p.Ser477Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 2.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,22995,23042" "T478K,T478K,S494P" "NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1480T>C" "YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Combination of RBD mutations appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome complicated by diffuse alveolar hemorrhage, who was receiving anticoagulation therapy, glucocorticoids, cyclophosphamide, and intermittent rituximab and eculizumab." "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23012" "S477N,E484K" "NC_045512.2:g.1430G>A,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~10x binding against this double mutation. Tixagevimab lost ~16x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was neutralized slightly less than D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "symptom prevalence" "" "" "Compared to the clade 20A strains that predominated during phase 1 between March and May 2020, the Marseille-4 variant (characterized by this mutation plus N:p.M234I;A376T) was associated with a lower frequency of cough, rhinitis, and olfactory and gustatory disorders. By contrast, hypoxemia was more frequent in patients infected with the Marseille-4 variant." "" "" "" "Fournier" "2021" "https://doi.org/10.1016/j.ijid.2021.03.068" "doi:10.1016/j.ijid.2021.03.068" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "22992,23399,23401,23402,23403" "S477N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1430G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "11 cases of re-infection with the 'Marseille-4' variant found within 1028 positive tests, where all of the earlier infections were from different strains. This lineage is also characterized by N:p.M234I;A376T" "" "" "" "Fournier" "2021" "https://doi.org/10.1016/j.ijid.2021.03.068" "doi:10.1016/j.ijid.2021.03.068" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23003" "N481Y" "NC_045512.2:g.1441A>T" "YP_009724390.1:p.Asn481Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Minor variant in initial round of in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009" "V483L" "NC_045512.2:g.1447G>C" "YP_009724390.1:p.Val483Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Remarkably, several of the E484 escape mutants were resistant to neutralization at the highest concentration (1:80 initial dilution) of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), all but one show major resistance." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, 1B07, SARS2-32, SARS2-35 and SARS2-07 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in all 4 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013" "E484A,E484A,E484A,E484A" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "'E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels'" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 152 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 152 S pseudotype was resistant to neutralization." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This Spike pseudotype for Day 152 virus from a chronically infected patient was completely resistent to REGN10933." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23018,23027,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1456T>A,NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 152 virus from a chronically infected patient: although mAb C1A-B12 had no activity against this pseudotype, all three affinity optimized versions were active; the antibody containing the most mutations, C1A-B12.3, was the most potent (IC50 <0.5 μg/mL)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2)." "" "" "" "Yuan" "2022" "https://doi.org/10.1101/2022.05.11.491588" "doi:10.1101/2022.05.11.491588" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous." "" "" "" "Braeye" "2022" "https://doi.org/10.1101/2022.05.09.22274623" "doi:10.1101/2022.05.09.22274623" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "3rd exposure to antigen by Delta (B.1.617.2) (n=24) breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a 3rd mRNA vaccine dose in individuals aged 21 –63 years, median age=30 years. Data collected 5.5 months after 2nd vaccination." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In sera from 17 sero-positive blood donors, and 18 months post-infection (May 2020) sera from 17 health care workers in Sweden, a 40x drop in neutralization by Omicron (B.1.1.529) pseudotyped lentivirus was observed in HEK293T cells using the First WHO International Standard (20/136). Median IC50 reduction was ~6x for the blood donors, and ~4.5x for the health care workers." "" "" "" "Sheward" "2021" "https://drive.google.com/file/d/1CuxmNYj5cpIuxWXhjjVmuDqntxXwlfXQ/view" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23009,23010,23012,23013,23071,23074,23075,22992,23060,23061,23062,23063" "E484A,E484A,E484A,E484A,Y505H,Y505H,Y505H,S477N,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1430G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using molecular dynamics simulation, ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations." "" "" "" "Zhang" "2022" "https://doi.org/10.1101/2022.06.05.493249" "doi:10.1101/2022.06.05.493249" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "This mutation occurred in 100% of sequenced virions after 12 passages and led to a 4-fold decrease in convalescent plasma neutralization activity" "" "" "" "Andreano" "2020" "https://doi.org/10.1101/2020.12.28.424451" "doi:10.1101/2020.12.28.424451" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage)" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~16x binding against this isolated mutation. Casirivimab lost ~16x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Human sera from 5 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) neutralized this variant 3.4x less relative to reference USA-WA1/2020 strain. 8 convalescent plasma with weak IgG ELISA titre neutralized this variant 2.4x less relative to reference USA-WA1/2020 strain. One plasma failed to neutralize at all. 11 convalescent plasma with moderate IgG ELISA titre neutralized this variant 4.2x less relative to reference USA-WA1/2020 strain. 11 convalescent plasma with high IgG ELISA titre neutralized this variant 2.6x less relative to reference USA-WA1/2020 strain." "" "" "" "Jangra" "2021" "https://doi.org/10.1016/S2666-5247(21" "doi:10.1016/S2666-5247(21" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Analyzing responses to the E484K mutation seen in B.1.351 and P.1 variants, we noted that it did not fall in a region predicted to bind the HLAII alleles tested (table S4). The mutation appeared to have no substantial or differential impact on T cell responses." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484K conferred a ten-fold reduction in neutralisation by vaccine sera." "" "" "" "Ferreira" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in all 4 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Monoclonal antibodies 13G9 and 58G6 maintain fairly high neutralization potency, compared to others interfacing with E484K." "" "" "" "Li" "2021" "https://doi.org/10.1101/2021.04.19.440481" "doi:10.1101/2021.04.19.440481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Multiple individuals in two related households were infected with a newly acquired E484K mutation within the B.1.311 lineage. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient's quarantine period." "" "" "" "Sabin" "2021" "https://doi.org/10.1101/2021.10.02.21264415" "doi:10.1101/2021.10.02.21264415" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2 antibodies C627, C602, C671, C643, and class 2/3 antibody C603 selected for the emergence of the E484K mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This variant alone shows a 10x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G." "" "" "" "Ferriera" "2021" "https://doi.org/10.1101/2021.05.08.443253" "doi:10.1101/2021.05.08.443253" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported moderate increase in affinity compared to wild-type RBD on the cell surface (Kd = 38.5nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "As measured by surface plasmon resonance, RBD with the E484K mutation alone showed a mean 19.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~20x binding against this isolated mutation. Casirivimab lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Of 50 mAbs tested, major loss of neutralization observed for S2N28, S2X615, S2N12, S2X192, S2H7, S2X16, S2X58, S2H70, S2X613, S2D19, S2N22, S2D32, S2H58, S2M11, S2D106, S2X30." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in binding efficiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus)" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed 3.3x reduction in IC50 serum dilution concentration for 6 convalescent sera." "" "" "" "Zhou" "2021" "https://doi.org/10.1101/2021.03.24.436620" "doi:10.1101/2021.03.24.436620" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs)." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape due to E484K [given Dec 2020-Apr 2021 time frame of the study, this is assumed to entail both Beta and Gamma lineages]." "" "" "" "Chung" "2021" "https://doi.org/10.1136/bmj.n1943" "doi:10.1136/bmj.n1943" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Neutralizing antibody titers of non-human primate sera after one or two doses of Ad26.COV2.S (Jannsen vaccine) against the variants containing the E484K substitution in the RBD were present but reduced (fold reduction between 3.35–7.78, 95% confidence interval all above twofold difference, one-sample t test)." "" "" "" "Solfrosi" "2021" "https://doi.org/10.1084/jem.20202756" "doi:10.1084/jem.20202756" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110)." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "The only mutation in the B.1.351 lineage that appears to contribute to neutralization reduction (~1.7x across 10 convalescent sera from April 2020 infectees)" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.6 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody VH-Fc ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-01, SARS2-02, 1B07, SARS2-16, SARS2-32, SARS2-35 and 2B04 of 10 antibodies tested, and moderately high resistance to the remaining." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">20% (ELISA significance threshold) drop in antibody binding by this variant against monoclonal antibody VH-Fc ab8." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "E484K pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed a mean 2.8x decrease in neutralization effiacacy." "" "" "" "Ikegame" "2021" "https://doi.org/10.21203/rs.3.rs-400230/v1" "doi:10.21203/rs.3.rs-400230/v1" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 15/20 convalescent sera was significantly lower against this pseudotyped virus model" "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484Q" "NC_045512.2:g.1450G>C" "YP_009724390.1:p.Glu484Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 3 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, E484Q shows a notably resistant profile, comparable to or even more resistant than E484K at later time points (i.e. more resistant to immune cell somatic mutation evolution), see Figure 5a,b. Subject C 32 days post-infection showed >>10 fold reduction in neutralization, reducing to ~10-fold by day 104. Subject B 26 days post-infection showed ~10 fold reduction in neutralization, reducing to ~4x at day 113. Notably, Subject B also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 32, and no E484K immune escape at day 104. Subject I 26 days post-infection showed ~10 fold reduction in neutralization, with no reduction in escape at day 102. Notably, Subject I also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 26, and no E484K immune escape at day 102." "" "" "" "Greaney" "2021" "https://doi.org/10.1016/j.chom.2021.02.003" "doi:10.1016/j.chom.2021.02.003" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Individual variants appearing at <=30% frequency at day 21 in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then appearing all at >95% frequency at day 27." "" "" "" "Chen" "2021" "https://doi.org/10.1101/2021.04.08.21254791" "doi:10.1101/2021.04.08.21254791" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012" "E484K" "NC_045512.2:g.1450G>A" "YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, ELISA tests show 10x reduced efficacy of a majority of isolated antibodies, but only a modest decrease for vaccine plasma overall." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22597,22599" "E484K,R346K,R346K" "NC_045512.2:g.1450G>A,NC_045512.2:g.1037G>A,NC_045512.2:g.1037G>A" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In serial experiment of mAb 2B04 resistent mutation isolate E484K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22810,22811,22812,22813,22813" "E484K,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~32x binding against this double mutation. COR-101 lost ~160x binding against this double mutation. Casirivimab lost ~16x binding against this double mutation. Estesevimab lost ~32x binding against this double mutation. Regdanvimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22810,22811,22812,22813,22813,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~13x more infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,22810,22811,22812,22813,22813,23399,23401,23402,23403" "E484K,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Approximately as infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of the individual variants)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23053,23054,23055,23060,23061,23062,23063" "E484K,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Omicron neutralizing antibodies is 0.722x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.5 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.4 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Omicron BA.5 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G" "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Omicron Molnupiravir (MK-4482) had no statistically significant change." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Log10ID50 of Omicron neutralizing antibodies is 0.686x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5." "" "" "" "McEvoy C" "2022" "https://doi.org/10.1101/2022.06.24.22276144" "doi:10.1101/2022.06.24.22276144" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Values taken 28 days after booster dose was given for BBIBP-CorVvaccine to 390 participants with 130 participants in the 0-14d-10m, 0-21d-10m and 0-28d-10m group. The geometric mean titers (GMT) of neutralizing antibody in 0-28d-10m and 0-21d-10m group were significantly higher than 0-14d-10m group at month 3, month 6 and month 10 after the second dose. A sharply decrease by 4.85-fold (GMT: 94.4-20.3), 4.67-fold (GMT: 134.4-28.8) and 4.49-fold (GMT: 145.5-32.4) was observed from day 28 to month 10 after the second dose in 0-14d-10m, 0-21d-10m and 0-28d-10m group, respectively, and they had similar decline kinetics." "" "" "" "Yao T" "2022" "https://doi.org/10.1101/2022.06.22.22276690" "doi:10.1101/2022.06.22.22276690" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Omicron BA.4 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently." "" "" "" "Neerukonda" "2022" "https://doi.org/10.1101/2022.06.01.494385" "doi:10.1101/2022.06.01.494385" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In the case of VOC B.1.1.7+E484K, the addition of the E484K mutation to N501Y further increased the affinity, to ~15 fold higher than WT RBD (KD ~5 nM), by further increasing the k(on) as measured by surface plasmon resonance. Because the higher k(on) could result in mass transfer limiting binding, we confirmed that the kinetic measurement for this variant was not substantially affected by varying levels of immobilization." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Viral load from lung tissue from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~17.5x folds more significant in 9 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~100x folds more significant in 3 individuals." "" "" "" "Arora" "2022" "https://doi.org/10.1038/s41423-022-00870-5" "doi:10.1038/s41423-022-00870-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR16m had a 0.025x fold change in IC50 in B.1.1.529 Omicron" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "Protection against symptomatic infection caused by Beta/Gamma (assumed by combined presence of N501Y and E484K) was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%)." "" "" "" "Nasreen" "2021" "https://doi.org/10.1101/2021.06.28.21259420" "doi:10.1101/2021.06.28.21259420" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)]" "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 20 sera from BNT162b2 mRNA vaccine inoculated participants, 6 displayed mild (2x) reductions in neutralization. This variant combination showed the highest reduction, but the magnitude of the differences was small compared to the >4x differences in HA-inhibition titers that have been used to signal potential need for a strain change in influenza vaccines." "" "" "" "Xie" "2021" "https://doi.org/10.1038/s41591-021-01270-4" "doi:10.1038/s41591-021-01270-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Trimeric proteins FSR22 had a 0.0015x fold change in IC50 in B.1.1.529 Omicron" "" "" "" "Chonira" "2022" "https://doi.org/10.1101/2022.05.30.493765" "doi:10.1101/2022.05.30.493765" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063" "E484K,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Viral load from oral swabs from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482." "" "" "" "Rosenke" "2022" "https://doi.org/10.1172/jci.insight.160108" "doi:10.1172/jci.insight.160108" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~6x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied]" "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~12x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of 501 and 484)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23060,23061,23062,23063,23399,23401,23402,23403" "E484K,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~11x, Vero ~10x, and Calu-3 ~11x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped viruses for B.1.618 was 2.7-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 3-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Pseudotyped viruses for B.1.618 was 2.5-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. [details on the convalescent patient sera collection are not abundantly clear in the preprint]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The estimated vaccine effectiveness against R.1 strain SARS-CoV-2 infection among residents in a Kentucky skilled nursing facility was 66.2% (95% CI = 40.5%–80.8%) and among health care workers was 75.9% (95% CI = 32.5%–91.4%) in the cohort of only those 14d+ post-vaccination Pfizer booster dose. VE against symptomatic COVID-19 was 86.5% (95% CI = 65.6%–94.7%) among residents and 87.1% (95% CI = 46.4%–96.9%) among HCP. VE against hospitalization was 94.4% (95% CI = 73.9%–98.8%) among residents; no HCP were hospitalized. Three residents died, two of whom were unvaccinated (VE = 94.4%; 95% CI = 44.6%–99.4%)." "" "" "" "Cavanaugh" "2021" "https://doi.org/10.15585/mmwr.mm7017e2" "doi:10.15585/mmwr.mm7017e2" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, RBD-specific mutation E484Q did not significantly confer infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484K,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 1.34x drop in neutralization (NT50) [mostly from a single serum]." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403" "E484Q,D614G,D614G,D614G,D614G" "NC_045512.2:g.1450G>C,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~4x infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the P.1 & P.2 lineages of SARS-CoV-2 in Brazil. The Brazilian arm of the Phase 3 double blind study showed severe/critical disease VE of 81.9% (95% CI: 17.0-98.1), and moderate to severe/critical disease VE of 66.2% (95% CI: 51.0-77.1). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 69.3% of mostly severe infections sequenced as of this report, 69.4% were of P.2 lineage [defining lineage SNPs reported here]." "" "" "" "" "2021" "https://www.fda.gov/media/146217/download" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped P.2 virus has reduced neutralization activity vs wild type: 5.8x (30 sera Pfizer median 9 days post 2nd dose) and 2.9x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23012,23399,23401,23402,23403,25088" "E484K,D614G,D614G,D614G,D614G,V1176F" "NC_045512.2:g.1450G>A,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3526G>T" "YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs]" "" "" "" "Sapkal" "2021" "https://doi.org/10.1101/2021.04.30.441559" "doi:10.1101/2021.04.30.441559" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23013" "E484V" "NC_045512.2:g.1451A>T" "YP_009724390.1:p.Glu484Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed in 4 separate mink farms in Denmark, but not humans, potential adaptation (diff set of farms than N501T)." "" "" "" "Oude Munnink" "2020" "https://doi.org/10.1126/science.abe5901" "doi:10.1126/science.abe5901" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.07 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486I" "NC_045512.2:g.1456T>A" "YP_009724390.1:p.Phe486Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutation causes a greater than 100x fold change in IC50 of Ensovibep." "" "" "" "Rothenberger" "2021" "https://doi.org/10.1101/2021.02.03.429164v4" "doi:10.1101/2021.02.03.429164v4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486L" "NC_045512.2:g.1456T>C" "YP_009724390.1:p.Phe486Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This mutation causes a greater than 100x fold change in IC50 of Ensovibep." "" "" "" "Rothenberger" "2021" "https://doi.org/10.1101/2021.02.03.429164v4" "doi:10.1101/2021.02.03.429164v4" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018" "F486V" "NC_045512.2:g.1456T>G" "YP_009724390.1:p.Phe486Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 5 antibodies." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" ">60% drop in antibody binding (ELISA) by this variant against monoclonal antibody VH-Fc ab8." "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed striking resistance with only 38% neutralization at the highest concentration tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 1 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.13 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "IC50 relative to wildtype drops ~8x in neutralization efficiency between 7-17 days post symptoms onset." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAbs SARS2-07, SARS2-19, 1B07, SARS2-16 and 2B04 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23018,23019" "F486S,F486S" "NC_045512.2:g.1457T>C,NC_045512.2:g.1457T>C" "YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Modest decrease in in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23023" "N487K" "NC_045512.2:g.1461T>G" "YP_009724390.1:p.Asn487Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, high ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.11 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escapes mAb REGN10933 (part of Regeneron's antibody cocktail)" "" "" "" "Starr" "2020" "https://doi.org/10.1101/2020.11.30.405472" "doi:10.1101/2020.11.30.405472" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Based on structural modelling, this change detected on day 128 sequencing in a chronically infected patient would alter an extensive network of polar interactions with antibody residue R94VH, a germline antibody residue that is conserved in all of the potent VH3-53/3-66-derived antibodies isolated from a convalescent donor 5 weeks after infection." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027" "Y489H" "NC_045512.2:g.1465T>C" "YP_009724390.1:p.Tyr489His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-32." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Strong reduction in neutralization capability of all 4 convalescent sera tested (3 ablations)." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2/3 mAb C603 modestly selected for the emergence of this mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-32 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "No effective neutralization in 3 out of the 4 sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23029,23030,23031" "F490S,F490S,F490S,F490S" "NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C,NC_045512.2:g.1469T>C" "YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected." "" "" "" "Witte" "2022" "https://doi.org/10.1101/2022.08.17.504313" "doi:10.1101/2022.08.17.504313" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23063" "Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This Spike pseudotype for Day 146 virus from a chronically infected patient was completely resistent to REGN10933. The variant had a 4-fold decrease in REGN10987 neutralization sensitivity (2nd component of the Regeneron mAb cocktail)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23063" "Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 146 virus from a chronically infected patient: resistant to neutralization by mAb C1A-B12, and was still resistant to the affinity enhanced antibodies derived from it (i.e. no affinity maturation effect on neutralization)." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23027,23060,23061,23062,23063" "Y489H,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1465T>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Pseudotype for Day 146 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 146 S pseudotype was resistant to neutralization." "" "" "" "Clark" "2021" "https://doi.org/10.1016/j.cell.2021.03.027" "doi:10.1016/j.cell.2021.03.027" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) resistant to 3 individual sera at >4x" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Positive selection (up to 23% of supernatant sequences) after C121 monoclonal antibody assay" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to some neutralizing antibodies: mAbs X593, 261-262, H4, and P2B-2F6" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490V" "NC_045512.2:g.1468T>G" "YP_009724390.1:p.Phe490Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody" "" "" "" "Greaney" "2020" "https://doi.org/10.1016/j.chom.2020.11.007" "doi:10.1016/j.chom.2020.11.007" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency." "" "" "" "Haslwanter" "2021" "https://doi.org/10.1101/2021.06.10.447999" "doi:10.1101/2021.06.10.447999" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23030" "F490L" "NC_045512.2:g.1468T>C" "YP_009724390.1:p.Phe490Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Complete loss of binding in ELISA by the variant against monoclonal antibody ab8" "" "" "" "Sun" "2021" "https://doi.org/10.1101/2021.03.22.436481" "doi:10.1101/2021.03.22.436481" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.1 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23031" "F490Y" "NC_045512.2:g.1469T>A" "YP_009724390.1:p.Phe490Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Dominant (70%) in day 21 of prolonged infection in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then nearly disappearing (<5%) by day 27." "" "" "" "Chen" "2021" "https://doi.org/10.1101/2021.04.08.21254791" "doi:10.1101/2021.04.08.21254791" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs." "" "" "" "Barnes" "2020" "https://doi.org/10.1038/s41586-020-2852-1" "doi:10.1038/s41586-020-2852-1" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R" "" "" "" "Weisblum" "2020" "https://doi.org/10.1101/2020.07.21.214759" "doi:10.1101/2020.07.21.214759" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Class 2 mAb C627 modestly selected for the emergence of this mutation in vitro." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant." "" "" "" "Gaebler" "2021" "https://doi.org/10.1101/2020.11.03.367391" "doi:10.1101/2020.11.03.367391" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Massive reduction in binding efficiency vs wild type for mAbs CB6/LY-CoV16 and LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23039,23040" "Q493R,Q493R" "NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G" "YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab)" "" "" "" "Starr" "2021" "https://doi.org/10.1101/2021.02.17.431683" "doi:10.1101/2021.02.17.431683" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "In 2 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, S484P shows a slightly resistant profile across both timepoints (i.e. resistant to immune cell somatic mutation evolution)" "" "" "" "Greaney" "2021" "https://doi.org/10.1016/j.chom.2021.02.003" "doi:10.1016/j.chom.2021.02.003" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01." "" "" "" "Liu" "2020" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555." "" "" "" "Rappazzo" "2021" "https://doi.org/10.1126/science.abf4830" "doi:10.1126/science.abf4830" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using molecular dynamic simulation, the mildly (~1kcal/mol) enhanced binding energy of this variant is primarily contributed by Tyr505 (−4.98 kcal/mol) which is now involved in a strong hydrogen bonding network with Arg393. Another important energetic contribution comes from the altered orientation of Tyr41 which is now involved with two hydrogen-bonding interactions with Asp355 and Thr500." "" "" "" "" "2021" "https://doi.org/10.1016/j.bbrc.2021.01.035" "doi:10.1016/j.bbrc.2021.01.035" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Highly resistant to mAb SARS2-01 of 10 antibodies tested." "" "" "" "Liu" "2020" "https://doi.org/10.1016/j.chom.2021.01.014" "doi:10.1016/j.chom.2021.01.014" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2020.11.06.372037" "doi:10.1101/2020.11.06.372037" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Minor variant selected in late rounds of an in vitro evolution experiment for ACE2 binding. Shown to increase the thermostability but decrease the association rate constant of the RBD to ACE2" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23042" "S494P" "NC_045512.2:g.1480T>C" "YP_009724390.1:p.Ser494Pro" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Regdanvimab lost ~32x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23048" "G496S" "NC_045512.2:g.1486G>A" "YP_009724390.1:p.Gly496Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23053,23054,23055,23060,23061,23062,23063" "Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. The extent of affinity increase with Q498R and N501Y is not exactly quantified, as E484K always emerged with this duo during in vitro evolution." "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Utilizing shark derived vnarbodies, S375F mutation on Omicron RBD disrupts the structure of β-strand, which inhibits binding with 20G6. 20G6 binds to a hidden epitope on RBD which is highly conserved in sarbecoviruses." "" "" "" "Feng" "2022" "https://doi.org/10.1002/smtd.202200387" "doi:10.1002/smtd.202200387" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C663, and to a lesser extent C613." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "Variant within the six key residues in the receptor binding domain (RBD). Independently reported in UK, Australia (same origin as UK), and South Africa (independent origin)." "" "" "" "Flores-Alanis" "2021" "https://doi.org/10.3390/pathogens10020184" "doi:10.3390/pathogens10020184" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome" "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a modest decrease in neutralization by vaccine plasma was observed." "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "In 30 samples collected 111 to 260 days post onset of symptoms, the covalescent plasma can neutralize both the reference USA-WA1/2020 strain and the mouse adapted strain that contains the N501Y spike mutation with similar efficiency." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine efficacy" "" "" "In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape by lineage Alpha [defined here as N501Y positive, but E484K negative]." "" "" "" "Chung" "2021" "https://doi.org/10.1136/bmj.n1943" "doi:10.1136/bmj.n1943" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3" "" "" "" "Wang" "2021" "https://doi.org/10.1101/2021.01.15.426911" "doi:10.1101/2021.01.15.426911" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Human sera from 6 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) can neutralize both the reference USA-WA1/2020 strain and the mouse adapted SARS-CoV-2 strain that contains the N501Y spike mutation with similar efficiency." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus." "" "" "" "Bates" "2021" "https://doi.org/10.1101/2021.04.04.21254881" "doi:10.1101/2021.04.04.21254881" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.69 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x)" "" "" "" "Shen" "2021" "https://doi.org/10.1101/2021.01.27.428516" "doi:10.1101/2021.01.27.428516" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Lowered the neutralization potency of mAb COVA1-12 to the limit of the assay. Decrease in potency was observed against the N501Y pseudotype for the cluster IX mAb COVA2-17." "" "" "" "Rees-Spear" "2021" "https://doi.org/10.1101/2021.01.15.426849" "doi:10.1101/2021.01.15.426849" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Vaccinated, but not post-infection sera, show decreased average T cell response to an N501Y peptide. When we primed transgenic mice expressing human HLA-DRB1*0401 with the Wuhan Hu-1 peptide pool, T cell responses to the B.1.1.7 variant peptide pool were significantly reduced (p = 0.0286). Furthermore, the T cell response to the spike N501Y mutation common to all three of the current VOC was ablated." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~8x binding against this isolated mutation. Regdanvimab lost ~6x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "1.2x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 and day 14 post-2nd dose) against a recombinant single variant virus (modified replicating WA-1 cDNA clone) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay." "" "" "" "Edara" "2021" "https://doi.org/10.1101/2021.02.02.21250799" "doi:10.1101/2021.02.02.21250799" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape." "" "" "" "Jacobson" "2021" "https://doi.org/10.1101/2021.04.14.21255431" "doi:10.1101/2021.04.14.21255431" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation alone accounts for most of the increased infectivity of the Alpha variant, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters, and Vero E6 (NHP) and Calu-3 (human) cell lines." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.03.08.434499" "doi:10.1101/2021.03.08.434499" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity." "" "" "" "Zhu" "2021" "https://doi.org/10.1101/2021.01.11.426269" "doi:10.1101/2021.01.11.426269" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Contrary to other reports on N501Y containing lineages (i.e. with additional mutations), N501Y alone may have an even greater affinity for a human monoclonal antibody specific for wild type. These results suggest that the individual N501Y mutation does not contribute to altered viral properties by itself, but may contribute to a collective conformational shift produced by multiple mutations." "" "" "" "Klegerman" "2021" "https://doi.org/10.1101/2021.04.26.441517" "doi:10.1101/2021.04.26.441517" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "As measured by surface plasmon resonance, RBD with the N501Y mutation alone showed a mean 2.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma." "" "" "" "Tang" "2021" "https://doi.org/10.1101/2021.03.19.436183" "doi:10.1101/2021.03.19.436183" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "0.7x reduction in neutralization by key variant in several variants of concern in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "~4-fold increase in binding affinity vs wild type." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In silico methods (PyMOL and PDBePISA) involving mutagenesis (N501Y mutation) and interface analysis focusing on the Spike RDB-ACE2 interaction showed that the SARS-CoV-2 N501Y mutant (lineage B.1.1.7) establishes a more significant number of interactions relating to the mutant residue Y501 (Spike RDB) with residues Y41 and K353 (ACE2). This finding shows that the increased infectivity of SARS-CoV-2 lineage B.1.1.7 is associated with the interaction force between the Spike RBD Y501 mutant residue with the ACE2 receptor, which in this strain is increased." "" "" "" "" "2021" "https://doi.org/10.1101/2020.12.29.424708" "doi:10.1101/2020.12.29.424708" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Experimentally, ACE2 binding affinity increased 0.24 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Of 50 mAbs tested, major loss of neutralization observed for S2X128, S2D8, S2X192, S2D19, S2H14, S2H19." "" "" "" "Collier" "2021" "https://doi.org/10.1038/s41586-021-03412-7" "doi:10.1038/s41586-021-03412-7" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM)" "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.02.02.428884" "doi:10.1101/2021.02.02.428884" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM)." "" "" "" "Tian" "2021" "https://doi.org/10.1101/2021.02.14.431117" "doi:10.1101/2021.02.14.431117" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM)." "" "" "" "Ramanathan" "2021" "https://doi.org/10.1101/2021.02.22.432359" "doi:10.1101/2021.02.22.432359" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The most frequent RBM mutation N501Y (165,519 instances) makes defective the atypical N-glycosylation sequon NGV 501-503, becoming a key RBM position for the interaction with hACE2-binding hotspot 353." "" "" "" "Gamez" "2021" "https://doi.org/10.1101/2021.04.09.439154" "doi:10.1101/2021.04.09.439154" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability." "" "" "" "Motozono" "2021" "https://doi.org/10.1101/2021.04.02.438288" "doi:10.1101/2021.04.02.438288" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slightly increased infection rate amongst the cells. [in what is essentially a replicate experiment in the same paper, because each B.1.351 lineage variant was independetly evaluated and N501 is in both lineages, a significant decrease was observed, therefore the error bars described in this paper should be interpreted carefully]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM)" "" "" "" "Zahradnik" "2021" "https://doi.org/10.1101/2021.01.06.425392" "doi:10.1101/2021.01.06.425392" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063" "N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "The N501Y mutation had the biggest effect on ACE2 affinity of any VOC mutation tested, increasing the affinity ~10 fold to KD ~7 nM, by increasing the k(on) ~1.8 fold and decreasing the k(off) by ~ 7 fold as measured by surface plasmon resonance." "" "" "" "Barton" "2021" "https://doi.org/10.1101/2021.05.18.444646" "doi:10.1101/2021.05.18.444646" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,22810,22811,22812,22813,22813" "N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "COR-101 lost ~20x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~6x binding against this double mutation. M396 lost ~10x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,22810,22811,22812,22813,22813,23012" "N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In post-vaccination sera from individuals who received one (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) of the BNT162b2 Pfizer vaccine, an average 6.8x reduction in neutralization efficacy of this B.1.351 key variants pseudotype lentivirus vs D614G was observed." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,22810,22811,22812,22813,22813,23012" "N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,E484K" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "~7x reduction in neutralization by key B.1.351 lineage RBD variant combination in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Two of the cohort showed no neutralization against this variant." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23012" "N501Y,N501Y,N501Y,N501Y,E484K" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "Bamlanivimab (LY-CoV555) lost ~64x binding against this double mutation. COR-101 lost ~50x binding against this double mutation. Casirivimab lost ~250x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~32x binding against this double mutation. Tixagevimab lost ~10x binding against this double mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23271" "N501Y,N501Y,N501Y,N501Y,A570D" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "reinfection" "" "" "Partial sequencing of S gene reveals two cases of probable early 2021 B.1.1.7 lineage reinfection from non-B.1.1.7 original cases in Lombardy, with 45 to 90 days between infections (less than the typical 90 day guideline for this call). Patients were 56 and 58yo, immunocompenent, with one a former smoker with obesity and dyslipidemia. One case required intubation during first infection, but presented with mild symptoms upon reinfection. The other case convalesced at home during the first episode, but required CPAP support in the subacute clinical unit upon reinfection." "" "" "" "Novazzi" "2021" "https://doi.org/10.1002/jmv.27066" "doi:10.1002/jmv.27066" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~13x, Vero ~10x, and Calu-3 ~10x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~9x, Vero ~8x, and Calu-3 ~8x. Compare to wild type at ~5x across cell types." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "This variant showed no change in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype)." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H ('Ohio') lineage was neutralized similarly to D614G in 10 convalescent sera from April 2020 infectees." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23399,23401,23402,23403,23593,23593" "N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,Q677H,Q677H" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2031G>T,NC_045512.2:g.2031G>C" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells for ACE2 affinity changes vs D614G alone, showing a ~70% drop in IC50 (i.e. increased affinity)." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23060,23061,23062,23063,23521,23522,23524,23525" "N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23071,23074,23075" "Y505H,Y505H,Y505H" "NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed first in a single tiger (cohort of 5), potential adaptation." "" "" "" "McAloose" "2020" "https://doi.org/10.1128/mBio.02220-20" "doi:10.1128/mBio.02220-20" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23071,23074,23075" "Y505H,Y505H,Y505H" "NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.16 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23102" "S514T" "NC_045512.2:g.1540T>A" "YP_009724390.1:p.Ser514Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.12 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23108" "E516Q" "NC_045512.2:g.1546G>C" "YP_009724390.1:p.Glu516Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.21 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23115" "L518Q" "NC_045512.2:g.1553T>A" "YP_009724390.1:p.Leu518Gln" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.06 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23120" "A520S" "NC_045512.2:g.1558G>T" "YP_009724390.1:p.Ala520Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "CR3022 (SARS-targeting mAb) cross-reactivity lost ~4x binding against this isolated mutation." "" "" "" "Engelhart" "2021" "https://doi.org/10.1101/2021.04.27.440939" "doi:10.1101/2021.04.27.440939" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23148" "K529T" "NC_045512.2:g.1586A>C" "YP_009724390.1:p.Lys529Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "gene expression increase" "" "" "Experimentally, Spike gene expression increased 0.15 fold" "" "" "" "Starr" "2020" "https://doi.org/10.1016/j.cell.2020.08.012" "doi:10.1016/j.cell.2020.08.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing statistically significant increased infection rate amongst the cells." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant raises PIWAS epitope score from 3.6% to 6.2% (improved immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23271" "A570D" "NC_045512.2:g.1709C>A" "YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated that there is very little free energy change (ddG. -0.02 kcal/mol) for this variant (i.e. approx. same stability as wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23373" "T604I" "NC_045512.2:g.1811C>T" "YP_009724390.1:p.Thr604Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Pseudotyped D614G virus has reduced neutralization activity vs wild type: 1.2x (37 sera Pfizer median 9 days post 2nd dose, 37 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA." "" "" "" "Garcia-Beltran" "2021" "https://doi.org/10.1016/j.cell.2021.03.013" "doi:10.1016/j.cell.2021.03.013" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.53x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a lentivirus virus pseudotyped with D614G Spike, sera from vaccinated individuals who received the second dose (9–11 days post-second dose of Pfizer) exhibited a robust neutralizing potential, with a mean NT50 value of 99,000. This was an average of a 2-fold increase, relative to sera drawn from the individuals who received one dose of vaccination—mean NT50 dilution of 51,300. Importantly, a 6-fold increase in mean NT50 dilution was obtained when sera from the first vaccination dose was compared to convalescent sera from cohort with severe disease (NT50 51,000 vs 8,700) 21 to 63 days post-onset." "" "" "" "Kuzmina" "2021" "https://doi.org/10.1016/j.chom.2021.03.008" "doi:10.1016/j.chom.2021.03.008" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 1.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 2.5 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "CryoEM shows increased proportion of 'one-up' trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Yurkovetskiy" "2020" "https://doi.org/10.1016/j.cell.2020.09.032" "doi:10.1016/j.cell.2020.09.032" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Negative stain EM shows increased proportion of 'one-up' trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2." "" "" "" "Weissman" "2020" "https://doi.org/10.1101/2020.07.22.20159905" "doi:10.1101/2020.07.22.20159905" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.97x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD mutation conferred a 4.85x drop in neutralization (NT50)." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "transmissibility" "" "" "Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 conferred a nearly two-fold infectivity advantage to the spike particles." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "In four cell lines (including 293T-hACE2 cells), this mutation combination increases infectivity vs D614G alone" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "Zhang" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion." "" "" "" "" "2020" "https://doi.org/10.1038/s41467-020-19808-4" "doi:10.1038/s41467-020-19808-4" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.05x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.45x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.35x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "tissue specific neutralization" "" "" "The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract." "" "" "" "Planas" "2021" "https://doi.org/10.1038/s41591-021-01318-5" "doi:10.1038/s41591-021-01318-5" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to wild type, D614G showed increased infectivity (ie. cold stability) after storage at -20°C for up to 30 days." "" "" "" "Huang" "2021" "https://doi.org/10.1128/msphere.00104-21" "doi:10.1128/msphere.00104-21" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation (a.k.a. 'Doug') outside the receptor binding domain, while highly favorable to improved human-human transmission, decreases transduction in naked mole-rat (Heterocephalus glaber) fibroblast and Japanese pipistrelle bat (Pipistrellus abramus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "The increased transduction with Spike D614G ranged from 1.3- to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2 and from 1.5- to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction." "" "" "" "Daniloski" "2021" "https://doi.org/10.7554/eLife.65365" "doi:10.7554/eLife.65365" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Studying 94 COVID-19 extended infection cases with genomics April 1 to October 17, 2020, one case developed 23 mutations in a 19 day period, including this combination in Spike." "" "" "" "Landis" "2021" "https://doi.org/10.1101/2021.05.08.21256775" "doi:10.1101/2021.05.08.21256775" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3)." "" "" "" "Kim" "2021" "https://doi.org/10.3390/v13040633" "doi:10.3390/v13040633" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "viral load" "" "" "Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission." "" "" "" "Plante" "2020" "https://doi.org/10.1038/s41586-020-2895-3" "doi:10.1038/s41586-020-2895-3" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses." "" "" "" "Ozono" "2020" "https://doi.org/10.1038/s41467-021-21118-2" "doi:10.1038/s41467-021-21118-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "syncytium formation" "" "" "Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation." "" "" "" "Mishra" "2021" "https://doi.org/10.1101/2021.10.04.463028" "doi:10.1101/2021.10.04.463028" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a slight decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403" "D614G,D614G,D614G,D614G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.43x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575" "D614G,D614G,D614G,D614G,L5F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.1x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575" "D614G,D614G,D614G,D614G,L5F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575" "D614G,D614G,D614G,D614G,L5F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.23x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664" "D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.526) showed a 1.78x increase in binding (KD) relative to D614G, even though each variant independently decreases binding." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664" "D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.526) showed a 1.34x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21575,21846,22317,22319,22320,23012,23664" "D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.13C>T,NC_045512.2:g.284C>T,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.526) showed a 1.02x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600" "D614G,D614G,D614G,D614G,S13I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600" "D614G,D614G,D614G,D614G,S13I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600" "D614G,D614G,D614G,D614G,S13I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.42x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600,22018,22915,22916,22917" "D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. [Stark contrast to 2.15x increase in binding by convalescent plasma 8 months post infection, presumably via memory B cell affinity maturation against L452R effects] 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600,22018,22915,22916,22917" "D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.429 aka Epsilon) showed a 2.82x increase in binding (KD) relative to D614G, indicating a strong marginal effect for L452R." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21600,22018,22915,22916,22917" "D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.38G>T,NC_045512.2:g.456G>T,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, indicating ablated marginal effect from L452R." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614" "D614G,D614G,D614G,D614G,L18F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.66x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Compare to decreased binding in full Spike variant complements for major lineages containing this variant subset: 0.96x (B.1.351 aka Beta), 0.77x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614" "D614G,D614G,D614G,D614G,L18F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.30x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.28x increase (B.1.351 aka Beta), and 1.14x decrease (P.1 aka Gamma). 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.17x increase (B.1.351 aka Beta), and 1.47x decrease (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614" "D614G,D614G,D614G,D614G,L18F" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.07x decrease in binding (KD) relative to D614G. Compare to increased binding in full Spike variant complements for major lineages containing this variant subset: 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing P.1 aka Gamma) showed a 4.24x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing P.1 aka Gamma) showed a 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21621,21638,21974,22132,22812,23012,23060,23061,23062,23063,23521,23522,23524,23525,24642" "D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.59C>A,NC_045512.2:g.76C>T,NC_045512.2:g.412G>T,NC_045512.2:g.570G>T,NC_045512.2:g.1250A>C,NC_045512.2:g.1450G>A,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing P.1 aka Gamma) showed a 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664" "D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing B.1.351 aka Beta) showed a 1.28x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. It shows a 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664" "D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.351 aka Beta) showed a 3.56x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21614,21801,23060,23061,23062,23063,22206,22810,22811,22812,22813,22813,23012,23664" "D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,E484K,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.52C>T,NC_045512.2:g.239A>C,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.644A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1450G>A,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing B.1.351 aka Beta) showed a 1.04x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, in contrast to the largely positive binding values for each individual mutation that comprises the set." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21621" "D614G,D614G,D614G,D614G,T20N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.39x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21621" "D614G,D614G,D614G,D614G,T20N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21621" "D614G,D614G,D614G,D614G,T20N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.59C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.96x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21638" "D614G,D614G,D614G,D614G,P26S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.23x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21638" "D614G,D614G,D614G,D614G,P26S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.58x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21638" "D614G,D614G,D614G,D614G,P26S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.76C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.33x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.51x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "This variant combination (representing B.1.1.7 aka Alpha) showed no change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.28x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.1.7 aka Alpha) had 5.43x increased binding relative to D614G alone." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21762,21763,21764,21765,21766,21766,21761,23060,23061,23062,23063,23271,23604,23709,24506,24914" "D614G,D614G,D614G,D614G,H69del,H69del,H69del,H69del,H69del,H69del,V70del,N501Y,N501Y,N501Y,N501Y,A570D,P681H,T716I,S982A,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1709C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.2147C>T,NC_045512.2:g.2944T>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "This variant combination (representing B.1.1.7 aka Alpha) showed a 1.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21801" "D614G,D614G,D614G,D614G,D80A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination showed no change relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21801" "D614G,D614G,D614G,D614G,D80A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.64x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.35x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21801" "D614G,D614G,D614G,D614G,D80A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.239A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21846" "D614G,D614G,D614G,D614G,T95I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21846" "D614G,D614G,D614G,D614G,T95I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21846" "D614G,D614G,D614G,D614G,T95I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.284C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21974" "D614G,D614G,D614G,D614G,D138Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21974" "D614G,D614G,D614G,D614G,D138Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,21974" "D614G,D614G,D614G,D614G,D138Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.412G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.32x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22018" "D614G,D614G,D614G,D614G,W152C" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.03x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22018" "D614G,D614G,D614G,D614G,W152C" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.15x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22018" "D614G,D614G,D614G,D614G,W152C" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.456G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22132" "D614G,D614G,D614G,D614G,R190S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.59x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22132" "D614G,D614G,D614G,D614G,R190S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22132" "D614G,D614G,D614G,D614G,R190S" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.570G>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.82x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22206" "D614G,D614G,D614G,D614G,D215G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.79x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22206" "D614G,D614G,D614G,D614G,D215G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.19x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22206" "D614G,D614G,D614G,D614G,D215G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.644A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D253G,D253G,D253G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.08x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D253G,D253G,D253G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22317,22319,22320" "D614G,D614G,D614G,D614G,D253G,D253G,D253G" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G,NC_045512.2:g.758A>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22810,22811,22812,22813,22813" "D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.76x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.75x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22810,22811,22812,22813,22813" "D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22810,22811,22812,22813,22813" "D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22812" "D614G,D614G,D614G,D614G,K417T" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22812" "D614G,D614G,D614G,D614G,K417T" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.28x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22812" "D614G,D614G,D614G,D614G,K417T" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1250A>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "2.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273)." "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.66x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.05x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.16x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,22915,22916,22917" "D614G,D614G,D614G,D614G,L452R,L452R,L452R" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G,NC_045512.2:g.1355T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by convalescent plasma [no cohort details provided]" "" "" "" "Wilhelm" "2021" "https://doi.org/10.1101/2021.08.09.21261704" "doi:10.1101/2021.08.09.21261704" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 4.2x-fold lower (95% CI: 0.15x-0.20x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 6.2-fold lower (95% CI: 11.8x-14.3x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 28.7x-fold lower (95% CI: 0.03x-0.05) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "4th antigenic exposure with Omicron (B.1.1.529 [BA.1])(n=29) infection increased variant specific plasma antibody and memory B cell responses as well as overall increased strain specific memory in individuals aged 22 –79 years, median age=33.5 years. Data collected 2.4 months after 3rd vaccination." "" "" "" "Wang" "2022" "https://doi.org/10.1101/2022.08.11.503601" "doi:10.1101/2022.08.11.503601" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 3.4-fold lower (95% CI: 3.2x-3.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23048,21762,21763,21764,21765,21766,21766,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,24130,23604,23039,23040,23053,23054,23055,22679,22686,22992,21846,22992,22995,21761,21987,21990,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G496S,H69del,H69del,H69del,H69del,H69del,H69del,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N856K,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,S373P,S375F,S477N,T95I,T478K,T478K,V70del,Y145del,Y145del,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1486G>A,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.204_209del,NC_045512.2:g.205_210del,NC_045512.2:g.204_209del,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2568C>A,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.284C>T,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.204_209del,NC_045512.2:g.432_434del,NC_045512.2:g.432_434del,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "paired testing of vaccine sera against ancestral virus compared to Omicron BA.1 shows that 3-dose vaccine regimen provides over 50x fold increase in protection against Omicron(B.1.1.529 [BA.1]) compared to a 2-dose regimen." "" "" "" "Hao" "2022" "https://doi.org/10.1101/2022.08.12.22278720" "doi:10.1101/2022.08.12.22278720" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 3.9x-fold lower (95% CI: 0.14x-0.17x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 4.5-fold lower (95% CI: 4.3x-4.7x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 78fM for binding to the Omicron BA.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold." "" "" "" "Uhal B" "2022" "https://doi.org/10.1101/2022.06.23.497326" "doi:10.1101/2022.06.23.497326" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 4.2-fold lower (95% CI: 5.8x-6.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23009,23010,23012,23013,21971,21972,21974,21976,21979,21981,21982,21984,21985,21986,21987,22576,22577,22578,23521,23522,23524,23525,22810,22811,22812,22813,22813,22917,22879,22881,22882,22882,23060,23061,23062,23063,23604,23039,23040,23053,23054,23055,22783,22784,22785,22786,22786,22679,22686,22992,22992,22995,23071,23074,23075" "D614G,D614G,D614G,D614G,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,P681H,Q493R,Q493R,Q498R,Q498R,Q498R,R408S,R408S,R408S,R408S,R408S,S373P,S375F,S477N,T478K,T478K,Y505H,Y505H,Y505H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.1451A>C,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.425G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1016G>A,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>T,NC_045512.2:g.1251G>C,NC_045512.2:g.1355T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>G,NC_045512.2:g.1320T>A,NC_045512.2:g.1320T>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.2042C>A,NC_045512.2:g.1478A>G,NC_045512.2:g.1478A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1493A>G,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>C,NC_045512.2:g.1224A>T,NC_045512.2:g.1224A>C,NC_045512.2:g.1117T>C,NC_045512.2:g.1124C>T,NC_045512.2:g.1430G>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1433C>A,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C,NC_045512.2:g.1513T>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 3.9x-fold lower (95% CI: 0.14x-0.18x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020." "" "" "" "Kurhade" "2022" "https://doi.org/10.1101/2022.06.05.494889" "doi:10.1101/2022.06.05.494889" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23012" "D614G,D614G,D614G,D614G,E484K" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.42x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23012" "D614G,D614G,D614G,D614G,E484K" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23012" "D614G,D614G,D614G,D614G,E484K" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1450G>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This variant appears twice in the experiments, with slightly different affinities (both ~1.2x decrease in binding relative to D614G) using flow cytometry and ACE2 ectodomains-Fc portion IgG complex." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23060,23061,23062,23063" "D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23060,23061,23062,23063" "D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23060,23061,23062,23063" "D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T,NC_045512.2:g.1501A>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.52x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis). Compare to full Spike variant complements for major lineages containing this variant subset: 5.43x (B.1.1.7 aka Alpha), 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23271" "D614G,D614G,D614G,D614G,A570D" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23271" "D614G,D614G,D614G,D614G,A570D" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.18x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23271" "D614G,D614G,D614G,D614G,A570D" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1709C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23521,23522,23524,23525" "D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.48x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23521,23522,23524,23525" "D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23521,23522,23524,23525" "D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.21x increase in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccine neutralization efficacy" "" "" "No significant change in virus neutralzation by 18 Pfizer two dose vaccinee sera compared to B.1.1.7. [results without including the used mutation A27S likely generalizable, as this is not a lineage defining mutation]" "" "" "" "Zuckerman" "2021" "https://doi.org/10.1101/2021.03.25.21253908" "doi:10.1101/2021.03.25.21253908" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23604" "D614G,D614G,D614G,D614G,P681H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2042C>A" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.26x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23664" "D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23664" "D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23664" "D614G,D614G,D614G,D614G,A701V" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2102C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed essentially no change in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23709" "D614G,D614G,D614G,D614G,T716I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23709" "D614G,D614G,D614G,D614G,T716I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.58x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,23709" "D614G,D614G,D614G,D614G,T716I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2147C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.12x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24506" "D614G,D614G,D614G,D614G,S982A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24506" "D614G,D614G,D614G,D614G,S982A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24506" "D614G,D614G,D614G,D614G,S982A" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.2944T>G" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.3x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24642" "D614G,D614G,D614G,D614G,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.56x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24642" "D614G,D614G,D614G,D614G,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.69x decrease in binding (KD) relative to D614G." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24642" "D614G,D614G,D614G,D614G,T1027I" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3080C>T" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.22x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24914" "D614G,D614G,D614G,D614G,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "vaccinee plasma binding" "" "" "1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24914" "D614G,D614G,D614G,D614G,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis)." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23399,23401,23402,23403,24914" "D614G,D614G,D614G,D614G,D1118H" "NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma binding" "" "" "1.96x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset." "" "" "" "Gong" "2021" "https://doi.org/10.1101/2021.08.04.455140" "doi:10.1101/2021.08.04.455140" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23429" "A623T" "NC_045512.2:g.1867G>A" "YP_009724390.1:p.Ala623Thr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain increases the virus transduction rate in tree shrew (Tupaia belangeri), (as it does in humans) according to pseudotyped VSV experiments." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Six minks were intranasally infected with WA1 isolate, all developed this mutation during infection." "" "" "" "Esclera" "2021" "https://doi.org/10.1101/2021.08.05.455290" "doi:10.1101/2021.08.05.455290" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 0.87 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23521,23522,23524,23525" "H655Y,H655Y,H655Y,H655Y" "NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T,NC_045512.2:g.1963C>T" "YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23587,23587" "Q675H,Q675H" "NC_045512.2:g.2025G>C,NC_045512.2:g.2025G>T" "YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly enhanced the ability of the pseudotyped VSV to infect fat-tailed gerbil (Pachyuromys duprasi) kidney cell cultures, with a transduction rate of 13.4%, close to the 15.7% in epithelial-like human Huh-7 cells while starting from a significantly lower wildtype (Wuhan-Hu-1 Spike VSVdeltaG psuedotype) rate." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "pharmaceutical effectiveness" "" "" "This individual mutation found in the epitope from Sotrovimab causes a 0.9x reduction in neutralization efficacy using a VSV model on Vero E6 cells." "" "" "" "Cathcart" "2021" "https://doi.org/10.1101/2021.03.09.434607v9" "doi:10.1101/2021.03.09.434607v9" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681R" "NC_045512.2:g.2042C>G" "YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. [PG: Inferred by conservative AA substitution of described P681H]" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681R" "NC_045512.2:g.2042C>G" "YP_009724390.1:p.Pro681Arg" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). [Inference from similar positively charged substitution P681H actually described in the work]" "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing NO statistically significant infection rate change amongst the cells, suggesting that furin cleavage typically used for cell entry is not affected by this change one amino acid upstream of the RXXR recognition pattern." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry)." "" "" "" "" "2021" "https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication" "" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676." "" "" "" "Chen" "2021" "https://doi.org/10.1038/s41591-021-01294-w" "doi:10.1038/s41591-021-01294-w" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "In the absence of N501Y, this Alpha lineage change in the furin clevage site did NOT show significant increase in infectivity relative to wild type, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters." "" "" "" "Liu" "2021" "https://doi.org/10.1101/2021.03.08.434499" "doi:10.1101/2021.03.08.434499" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic." "" "" "" "Johnson" "2020" "https://doi.org/10.1101/2020.08.26.268854" "doi:10.1101/2020.08.26.268854" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604" "P681H" "NC_045512.2:g.2042C>A" "YP_009724390.1:p.Pro681His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "While the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC)." "" "" "" "Lubinski" "2021" "https://doi.org/10.1101/2021.04.06.438731" "doi:10.1101/2021.04.06.438731" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23604,23399,23401,23402,23403" "P681R,D614G,D614G,D614G,D614G" "NC_045512.2:g.2042C>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G,NC_045512.2:g.1841A>G" "YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Quantification of the band intensities showed that the P681R mutation, which lies near the proteolytic processing site, caused a small increase in proteolytic processing as measured by a 2-fold decrease in the ratio of S/S2." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.05.14.444076" "doi:10.1101/2021.05.14.444076" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23664" "A701V" "NC_045512.2:g.2102C>T" "YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23664" "A701V" "NC_045512.2:g.2102C>T" "YP_009724390.1:p.Ala701Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is -0.33 kcal/mol (i.e. destabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant increases PIWAS epitope score from 0.69% to 2.3% Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Observed first in a single tiger (cohort of 5), potential adaptation." "" "" "" "McAloose" "2020" "https://doi.org/10.1128/mBio.02220-20" "doi:10.1128/mBio.02220-20" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain showed a decreased capacity to transduce PK-15 (pig kidney, Sus scrofa) and PaKi (black flying fox kidney, Pteropus alecto) cell line cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23709" "T716I" "NC_045512.2:g.2147C>T" "YP_009724390.1:p.Thr716Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. T716I was expressed at significantly lower level, accounting for the decreased infectivity of this spike protein. This property may be specific to spike protein biosynthesis in 293T cells and is not likely to reflect the situation in vivo given the reported increase in infectivity of the B.1.1.7 virus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23897" "Q779K" "NC_045512.2:g.2335C>A" "YP_009724390.1:p.Gln779Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "monoclonal antibody serial passage escape" "" "" "Escape variant 20% appearance in 2 passages against Regeneron monoclonal antibody RGN10989 @ 50ug/mL" "" "" "" "Baum" "2020" "https://doi.org/10.1126/science.abd0831" "doi:10.1126/science.abd0831" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "23948" "D796H" "NC_045512.2:g.2386G>C" "YP_009724390.1:p.Asp796His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Fatal COVID-19 complications in immunocomprimised patient after immune escape from convalescent plasma" "" "" "" "Kemp" "2020" "https://doi.org/10.1101/2020.12.05.20241927" "doi:10.1101/2020.12.05.20241927" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24000" "S813I" "NC_045512.2:g.2438G>T" "YP_009724390.1:p.Ser813Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape)" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Resistent to neutralizing mAb B38" "" "" "" "Li" "2020" "https://doi.org/10.1016/j.cell.2020.07.012" "doi:10.1016/j.cell.2020.07.012" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24054" "A831V" "NC_045512.2:g.2492C>T" "YP_009724390.1:p.Ala831Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry)" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24077" "D839Y" "NC_045512.2:g.2515G>T" "YP_009724390.1:p.Asp839Tyr" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry." "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24077" "D839N" "NC_045512.2:g.2515G>A" "YP_009724390.1:p.Asp839Asn" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry." "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24130" "N856K" "NC_045512.2:g.2568C>A" "YP_009724390.1:p.Asn856Lys" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "branch specific selection pressure" "" "" "Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch." "" "" "" "Lucaci" "2021" "https://observablehq.com/@aglucaci/sc2-omicron" "" "" "" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24170" "I870V" "NC_045512.2:g.2608A>G" "YP_009724390.1:p.Ile870Val" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Appeared at same time as T478K,S494P but listed separately due to distance and different domains affected in the Spike (i.e. putatively an independent mutation from a functional standpoint since the former are from S1, the latter from S2)." "" "" "" "Choi" "2020" "https://doi.org/10.1056/NEJMc2031364" "doi:10.1056/NEJMc2031364" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24377,24378" "S939F,S939F" "NC_045512.2:g.2816C>T,NC_045512.2:g.2816C>T" "YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay." "" "" "" "Li" "2023" "https://doi.org/10.1038/s41396-023-01368-2" "doi:10.1038/s41396-023-01368-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (70%) increase in infection rate amongst the cells, hence this individual variant is likely to significantly contribute to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "environmental condition stability" "" "" "Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour" "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "ACE2 receptor binding affinity" "" "" "This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "The neutralizing activity of 6/20 convalescent sera was significantly lower against this single variant pseudotyped virus model, showing similar patterns to the pseudotyped virus model of B.1.1.7." "" "" "" "Wang" "2021" "https://doi.org/10.1038/s41586-021-03398-2" "doi:10.1038/s41586-021-03398-2" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24506" "S982A" "NC_045512.2:g.2944T>G" "YP_009724390.1:p.Ser982Ala" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24642" "T1027I" "NC_045512.2:g.3080C>T" "YP_009724390.1:p.Thr1027Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "virion structure" "" "" "Estimated free energy change (ddG) for this variant is 1.51 kcal/mol (i.e. stabilizing relative to wild type)" "" "" "" "Spratt" "2021" "https://doi.org/10.1101/2021.03.24.436850" "doi:10.1101/2021.03.24.436850" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "T cell evasion" "" "" "Mutation is predicted to lose the T cell epitope for people carrying DRB1*0301 and DRB1*0401, but not for example in those who are DRB1*0701 or DRB1*1501 who would be predicted to show an enhanced response. This is also observed in a study of 26 each post-infection and post first dose HCWs." "" "" "" "Reynolds" "2021" "https://doi.org/10.1126/science.abh1282" "doi:10.1126/science.abh1282" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "24914" "D1118H" "NC_045512.2:g.3352G>C" "YP_009724390.1:p.Asp1118His" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "antibody epitope effects" "" "" "Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25046" "P1162S" "NC_045512.2:g.3484C>T" "YP_009724390.1:p.Pro1162Ser" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "convalescent plasma escape" "" "" "Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection." "" "" "" "Schmidt" "2021" "https://doi.org/10.1101/2021.08.06.455491" "doi:10.1101/2021.08.06.455491" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25249,25249,25249" "M1229I,M1229I,M1229I" "NC_045512.2:g.3687G>C,NC_045512.2:g.3687G>A,NC_045512.2:g.3687G>T" "YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness." "" "" "" "Tada" "2021" "https://doi.org/10.1101/2021.02.05.430003" "doi:10.1101/2021.02.05.430003" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25350" "P1263L" "NC_045512.2:g.3788C>T" "YP_009724390.1:p.Pro1263Leu" "" "surface glycoprotein gene (SARS-CoV-2)" "s gene (SARS-CoV-2)" "surface glycoprotein (SARS-CoV-2)" "S protein (SARS-CoV-2)" "trafficking" "" "" "Circulating variant in the cytoplasmic tail, shown in vitro to increase Spike subunit fusion required for cell entry" "" "" "" "Barrett" "2021" "https://doi.org/10.1101/2021.01.24.428007" "doi:10.1101/2021.01.24.428007" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "25855" "D155Y" "NC_045512.2:g.463G>T" "YP_009724391.1:p.Asp155Tyr" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "caveolin binding" "" "" "In silico, this mutation is the only one weakening ORF3a's binding affinity for caveolin-1 (essential for entry and endomembrane trafficking of SARS-CoV-2). This mutation is a widespread homoplasy in 20A and 20B lineages." "" "" "" "Gupta" "2021" "https://doi.org/10.1101/2021.03.26.437194" "doi:10.1101/2021.03.26.437194" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26029" "Q213K" "NC_045512.2:g.637C>A" "YP_009724391.1:p.Gln213Lys" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*01:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26029" "Q213K" "NC_045512.2:g.637C>A" "YP_009724391.1:p.Gln213Lys" "" "open reading frame 3a gene (SARS-CoV-2)" "orf3a gene (SARS-CoV-2)" "open reading frame 3a protein (SARS-CoV-2)" "Orf3a protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*01:01-restricted CD8+ ORF3a epitope, which is otherwise 'consistently dominant and of high magnitude'." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26256" "F4F" "NC_045512.2:g.12C>T" "YP_009724392.1:p.Phe4Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26268,26269,26270" "T9I,T9I,T9I" "NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T" "YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~300 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26268,26269,26270" "T9I,T9I,T9I" "NC_045512.2:g.26C>T,NC_045512.2:g.26C>T,NC_045512.2:g.26C>T" "YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26296" "L18I" "NC_045512.2:g.52C>A" "YP_009724392.1:p.Leu18Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (47x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26299" "L19F" "NC_045512.2:g.55C>T" "YP_009724392.1:p.Leu19Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26312" "F23C" "NC_045512.2:g.68T>G" "YP_009724392.1:p.Phe23Cys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~8.8 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26314" "V24M" "NC_045512.2:g.70G>A" "YP_009724392.1:p.Val24Met" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26319" "V25V" "NC_045512.2:g.75A>G" "YP_009724392.1:p.Val25Val" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (45x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26333" "T30I" "NC_045512.2:g.89C>T" "YP_009724392.1:p.Thr30Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26353" "L37F" "NC_045512.2:g.109C>T" "YP_009724392.1:p.Leu37Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26395" "L51I" "NC_045512.2:g.151C>A" "YP_009724392.1:p.Leu51Ile" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (47x overrepresentation vs expected count of ~24 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26416" "V58L" "NC_045512.2:g.172G>C" "YP_009724392.1:p.Val58Leu" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26428" "V62F" "NC_045512.2:g.184G>T" "YP_009724392.1:p.Val62Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (18x overrepresentation vs expected count of ~333 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26442" "N66K" "NC_045512.2:g.198T>G" "YP_009724392.1:p.Asn66Lys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~23 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26447" "S68F" "NC_045512.2:g.203C>T" "YP_009724392.1:p.Ser68Phe" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26447" "S68C" "NC_045512.2:g.203C>G" "YP_009724392.1:p.Ser68Cys" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (58x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26456" "P71R" "NC_045512.2:g.212C>G" "YP_009724392.1:p.Pro71Arg" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26467" "V75L" "NC_045512.2:g.223G>C" "YP_009724392.1:p.Val75Leu" "" "envelope gene (SARS-CoV-2)" "e gene (SARS-CoV-2)" "envelope protein (SARS-CoV-2)" "E protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (3762.7x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526" "A2S" "NC_045512.2:g.4G>T" "YP_009724393.1:p.Ala2Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (38x overrepresentation vs expected count of ~334 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526" "A2S" "NC_045512.2:g.4G>T" "YP_009724393.1:p.Ala2Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Emergent as 16% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing." "" "" "" "Avanzato" "2020" "https://doi.org/10.1016/j.cell.2020.10.049" "doi:10.1016/j.cell.2020.10.049" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26526,26527,26529" "D3H,D3H,D3H" "NC_045512.2:g.7G>C,NC_045512.2:g.7G>C,NC_045512.2:g.7G>C" "YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (227x overrepresentation vs expected count of ~14 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26528,26528,26528" "A2A,A2A,A2A" "NC_045512.2:g.6A>T,NC_045512.2:g.6A>G,NC_045512.2:g.6A>C" "YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (25x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26530" "D3G" "NC_045512.2:g.8A>G" "YP_009724393.1:p.Asp3Gly" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (31x overrepresentation vs expected count of ~53 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26542" "T7I" "NC_045512.2:g.20C>T" "YP_009724393.1:p.Thr7Ile" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26546" "I8I" "NC_045512.2:g.24T>C" "YP_009724393.1:p.Ile8Ile" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~80 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26573,26576,26577" "Q19E,Q19E,Q19E" "NC_045512.2:g.55C>G,NC_045512.2:g.55C>G,NC_045512.2:g.55C>G" "YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~8 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26620" "C33S" "NC_045512.2:g.98G>C" "YP_009724393.1:p.Cys33Ser" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~32 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26645" "N41N" "NC_045512.2:g.123C>T" "YP_009724393.1:p.Asn41Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (19x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26681" "F53F" "NC_045512.2:g.159C>T" "YP_009724393.1:p.Phe53Phe" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (163x overrepresentation vs expected count of ~567 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26730" "V70L" "NC_045512.2:g.208G>C" "YP_009724393.1:p.Val70Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26748" "I76V" "NC_045512.2:g.226A>G" "YP_009724393.1:p.Ile76Val" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26748" "I76L" "NC_045512.2:g.226A>C" "YP_009724393.1:p.Ile76Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~9 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26749" "I76T" "NC_045512.2:g.227T>C" "YP_009724393.1:p.Ile76Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (19x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26767" "I82T" "NC_045512.2:g.245T>C" "YP_009724393.1:p.Ile82Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "homoplasy" "" "" "This mutation presents mainly within the B.1 (44.0%) and B.1.525 (38.1%) lineages. Currently, 99.7% of the B.1.525 lineage isolates carry the M:I82T mutation. While this mutation is scattered across multiple phylogenetic clades, most cases cluster in two recent clades, suggesting a likely selective advantage in certain haplotype backgrounds." "" "" "" "Shen" "2021" "https://doi.org/10.1080/22221751.2021.1922097" "doi:10.1080/22221751.2021.1922097" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26767" "I82T" "NC_045512.2:g.245T>C" "YP_009724393.1:p.Ile82Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (67x overrepresentation vs expected count of ~42 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26801,26801,26801" "L93L,L93L,L93L" "NC_045512.2:g.279C>G,NC_045512.2:g.279C>A,NC_045512.2:g.279C>T" "YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~628 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26855,26858" "F112F,F112F" "NC_045512.2:g.336C>T,NC_045512.2:g.336C>T" "YP_009724393.1:p.Phe112Phe,YP_009724393.1:p.Phe112Phe" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~463 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26861" "N113N" "NC_045512.2:g.339T>C" "YP_009724393.1:p.Asn113Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (57x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26873" "N117N" "NC_045512.2:g.351C>T" "YP_009724393.1:p.Asn117Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26882,26882" "L120L,L120L" "NC_045512.2:g.360C>A,NC_045512.2:g.360C>T" "YP_009724393.1:p.Leu120Leu,YP_009724393.1:p.Leu120Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26894,26894" "L124L,L124L" "NC_045512.2:g.372C>T,NC_045512.2:g.372C>G" "YP_009724393.1:p.Leu124Leu,YP_009724393.1:p.Leu124Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26895" "H125Y" "NC_045512.2:g.373C>T" "YP_009724393.1:p.His125Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARA_CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26895" "H125Y" "NC_045512.2:g.373C>T" "YP_009724393.1:p.His125Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (22x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26907,26909,26909" "L129L,L129L,L129L" "NC_045512.2:g.385C>T,NC_045512.2:g.387G>A,NC_045512.2:g.387G>T" "YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26927" "E135E" "NC_045512.2:g.405A>G" "YP_009724393.1:p.Glu135Glu" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (232x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26951,26951,26951" "V143V,V143V,V143V" "NC_045512.2:g.429G>C,NC_045512.2:g.429G>A,NC_045512.2:g.429G>T" "YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~508 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26966" "H148H" "NC_045512.2:g.444T>C" "YP_009724393.1:p.His148His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26972" "R150R" "NC_045512.2:g.450T>C" "YP_009724393.1:p.Arg150Arg" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~89 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26985" "H155N" "NC_045512.2:g.463C>A" "YP_009724393.1:p.His155Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (20x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "26987" "H155H" "NC_045512.2:g.465T>C" "YP_009724393.1:p.His155His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27021" "E167Q" "NC_045512.2:g.499G>C" "YP_009724393.1:p.Glu167Gln" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27035,27038" "T172T,T172T" "NC_045512.2:g.516A>G,NC_045512.2:g.516A>G" "YP_009724393.1:p.Thr172Thr,YP_009724393.1:p.Thr172Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27059" "Y179Y" "NC_045512.2:g.537C>T" "YP_009724393.1:p.Tyr179Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27112" "S197T" "NC_045512.2:g.590G>C" "YP_009724393.1:p.Ser197Thr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (18x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27134" "Y204Y" "NC_045512.2:g.612T>C" "YP_009724393.1:p.Tyr204Tyr" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (29x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27143" "N207N" "NC_045512.2:g.621C>T" "YP_009724393.1:p.Asn207Asn" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27147" "D209H" "NC_045512.2:g.625G>C" "YP_009724393.1:p.Asp209His" "" "membrane glycoprotein gene (SARS-CoV-2)" "m gene (SARS-CoV-2)" "membrane glycoprotein (SARS-CoV-2)" "M protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (81x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "27367" "Q56X" "NC_045512.2:g.166C>T" "YP_009724394.1:p.Gln56Xaa" "" "open reading frame 6 gene (SARS-CoV-2)" "orf6 gene (SARS-CoV-2)" "open reading frame 6 protein (SARS-CoV-2)" "Orf6 protein (SARS-CoV-2)" "IFN activity" "" "" "The residues listed are determinants of the potent IFN-antagonistic activity of SARS-CoV-2 ORF6 (via blocking mRNA nuclear export)" "" "" "" "Kimura" "2020" "https://doi.org/10.2139/ssrn.3690468" "doi:10.2139/ssrn.3690468" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28144" "L84S" "NC_045512.2:g.251T>C" "YP_009724396.1:p.Leu84Ser" "" "open reading frame 8 gene (SARS-CoV-2)" "orf8 gene (SARS-CoV-2)" "open reading frame 8 protein (SARS-CoV-2)" "Orf8 protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28307,28309,28310,28311" "P13L,P13L,P13L,P13L" "NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T" "YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13)." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28307,28309,28310,28311" "P13L,P13L,P13L,P13L" "NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T,NC_045512.2:g.38C>T" "YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28310" "P13S" "NC_045512.2:g.37C>T" "YP_009724397.2:p.Pro13Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*27:05." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28310" "P13S" "NC_045512.2:g.37C>T" "YP_009724397.2:p.Pro13Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13)." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28769" "T166A" "NC_045512.2:g.496A>G" "YP_009724397.2:p.Thr166Ala" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "Confers a significant PIWAS value decrease (reduced antigenicity)" "" "" "" "Haynes" "2020" "https://doi.org/10.1101/2020.11.23.20235002" "doi:10.1101/2020.11.23.20235002" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28853" "S194T" "NC_045512.2:g.580T>A" "YP_009724397.2:p.Ser194Thr" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "anthropozoonotic events" "" "" "Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains." "" "" "" "Rathnasinghe" "2021" "https://doi.org/10.1101/2021.01.19.21249592" "doi:10.1101/2021.01.19.21249592" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28854" "S194L" "NC_045512.2:g.581C>T" "YP_009724397.2:p.Ser194Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "outcome hazard ratio" "" "" "In March 2021 this variant had an allele frequency of 47.62 and 7.25% in deceased patients, compared to 35.16 and 3.20% of the same variant in recovered patients, from the Gujarat and global datasets." "" "" "" "Joshi" "2021" "https://doi.org/10.3389/fgene.2021.586569" "doi:10.3389/fgene.2021.586569" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28854" "S194L" "NC_045512.2:g.581C>T" "YP_009724397.2:p.Ser194Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "Mutation with a population frequency of 30% in a Mexican dataset, primarily of lineage 20B, but also present in a substantial number of 20A lineage sequences, suggesting convergent evolution." "" "" "" "Barona-Gomez" "2021" "https://doi.org/10.1101/2021.05.18.21256128" "doi:10.1101/2021.05.18.21256128" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28869" "P199L" "NC_045512.2:g.596C>T" "YP_009724397.2:p.Pro199Leu" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28879" "S202R" "NC_045512.2:g.606T>G" "YP_009724397.2:p.Ser202Arg" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows major increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28881" "R203M" "NC_045512.2:g.608G>T" "YP_009724397.2:p.Arg203Met" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "RNA binding" "" "" "Northern blot analysis of novel mutant virus-like-particles (VLPs) shows most increase in RNA content of any N mutation tested, suggesting that this mutation improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP)." "" "" "" "Syed" "2021" "https://doi.org/10.1101/2021.08.05.455082" "doi:10.1101/2021.08.05.455082" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "28977" "S235F" "NC_045512.2:g.704C>T" "YP_009724397.2:p.Ser235Phe" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "variant linear antibody epitope effects" "" "" "Substantially increases epitope and antigen scores in 2 of 579 individuals (should increase immune response). In the B1.1.7 lineage this is largely counteracted by the D3L mutation, which decreases PIWAS signal significantly in 1.5% of COVID patients, for a net neutral effect at the population level." "" "" "" "Haynes" "2021" "https://doi.org/10.1101/2021.01.06.20248960" "doi:10.1101/2021.01.06.20248960" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29239,29239" "M322I,M322I" "NC_045512.2:g.966G>A,NC_045512.2:g.966G>T" "YP_009724397.2:p.Met322Ile,YP_009724397.2:p.Met322Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "Agerer" "2021" "https://doi.org/10.1126/sciimmunol.abg6461" "doi:10.1126/sciimmunol.abg6461" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29247" "T325I" "NC_045512.2:g.974C>T" "YP_009724397.2:p.Thr325Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29247" "T325I" "NC_045512.2:g.974C>T" "YP_009724397.2:p.Thr325Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes partial loss of T cell line responsiveness and CTL killing ability by B*40:01-restricted CD8+ N epitope MEVTPSGTWL 322-331." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29266,29266" "L331F,L331F" "NC_045512.2:g.993G>T,NC_045512.2:g.993G>C" "YP_009724397.2:p.Leu331Phe,YP_009724397.2:p.Leu331Phe" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01." "" "" "" "Agerer" "2021" "https://doi.org/10.1126/sciimmunol.abg6461" "doi:10.1126/sciimmunol.abg6461" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is 'consistently dominant and of high magnitude'." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29358" "T362I" "NC_045512.2:g.1085C>T" "YP_009724397.2:p.Thr362Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is 'consistently dominant and of high magnitude'." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29366" "P365S" "NC_045512.2:g.1093C>T" "YP_009724397.2:p.Pro365Ser" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "T cell evasion" "" "" "This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01." "" "" "" "de Silva" "2021" "https://doi.org/10.1101/2021.04.08.438904" "doi:10.1101/2021.04.08.438904" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "29409" "T379I" "NC_045512.2:g.1136C>T" "YP_009724397.2:p.Thr379Ile" "" "nucleocapsid phosphoprotein gene (SARS-CoV-2)" "n gene (SARS-CoV-2)" "nucleocapsid phosphoprotein (SARS-CoV-2)" "N protein (SARS-CoV-2)" "homoplasy" "" "" "In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent." "" "" "" "Borges" "2021" "https://doi.org/10.1101/2021.05.19.444774" "doi:10.1101/2021.05.19.444774" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "335" "R24C" "NC_045512.2:g.70C>T" "YP_009724389.1:p.Arg24Cys" "YP_009724389.1:Arg24Cys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (25x overrepresentation vs expected count of 514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "347" "V28I" "NC_045512.2:g.82G>A" "YP_009724389.1:p.Val28Ile" "YP_009724389.1:Val28Ile" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (30x overrepresentation vs expected count of 143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "383" "S40P" "NC_045512.2:g.118T>C" "YP_009724389.1:p.Ser40Pro" "YP_009724389.1:Ser40Pro" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (16x overrepresentation vs expected count of ~58 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "396" "Q44L" "NC_045512.2:g.131A>T" "YP_009724389.1:p.Gln44Leu" "YP_009724389.1:Gln44Leu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (11x overrepresentation vs expected count of ~19 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "443" "V60I" "NC_045512.2:g.178G>A" "YP_009724389.1:p.Val60Ile" "YP_009724389.1:Val60Ile" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "489" "D75G" "NC_045512.2:g.224A>G" "YP_009724389.1:p.Asp75Gly" "YP_009724389.1:Asp75Gly" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "490,490" "D75E,D75E" "NC_045512.2:g.225T>G,NC_045512.2:g.225T>A" "YP_009724389.1:p.Asp75Glu,YP_009724389.1:p.Asp75Glu" "YP_009724389.1:Asp75Glu,YP_009724389.1:Asp75Glu" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (15x overrepresentation vs expected count of ~20 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "immunosuppression variant emergence" "" "" "Emergent as 22% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing." "" "" "" "Avanzato" "2020" "https://doi.org/10.1016/j.cell.2020.10.049" "doi:10.1016/j.cell.2020.10.049" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 500-523) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-517) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520" "M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del" "NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.252_254del,NC_045512.2:g.253_255del,NC_045512.2:g.253_255del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del,NC_045512.2:g.257_259del" "YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del" "YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Met85del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del,YP_009724389.1:Val86del" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "IFN activity" "" "" "Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-523) was tested in vitro for IFN response." "" "" "" "Lin" "2021" "https://doi.org/10.1016/j.chom.2021.01.015" "doi:10.1016/j.chom.2021.01.015" "" "true" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "507,509,518" "M85V,M85V,M85V" "NC_045512.2:g.253A>G,NC_045512.2:g.253A>G,NC_045512.2:g.253A>G" "YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val" "YP_009724389.1:Met85Val,YP_009724389.1:Met85Val,YP_009724389.1:Met85Val" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "508" "H81Q" "NC_045512.2:g.243T>A" "YP_009724389.1:p.His81Gln" "YP_009724389.1:His81Gln" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (30x overrepresentation vs expected count of ~20 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "510" "M85K" "NC_045512.2:g.254T>A" "YP_009724389.1:p.Met85Lys" "YP_009724389.1:Met85Lys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~12 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "561" "R99H" "NC_045512.2:g.296G>A" "YP_009724389.1:p.Arg99His" "YP_009724389.1:Arg99His" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (17x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "563" "S100C" "NC_045512.2:g.298A>T" "YP_009724389.1:p.Ser100Cys" "YP_009724389.1:Ser100Cys" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (33x overrepresentation vs expected count of ~19 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "593" "H110Y" "NC_045512.2:g.328C>T" "YP_009724389.1:p.His110Tyr" "YP_009724389.1:His110Tyr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (22x overrepresentation vs expected count of ~514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "593" "H110D" "NC_045512.2:g.328C>G" "YP_009724389.1:p.His110Asp" "YP_009724389.1:His110Asp" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (12x overrepresentation vs expected count of ~11 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "606" "I114T" "NC_045512.2:g.341T>C" "YP_009724389.1:p.Ile114Thr" "YP_009724389.1:Ile114Thr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (155x overrepresentation vs expected count of ~58 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "657" "A131V" "NC_045512.2:g.392C>T" "YP_009724389.1:p.Ala131Val" "YP_009724389.1:Ala131Val" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~514 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "677" "A138T" "NC_045512.2:g.412G>A" "YP_009724389.1:p.Ala138Thr" "YP_009724389.1:Ala138Thr" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (14x overrepresentation vs expected count of ~143 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "761" "S166G" "NC_045512.2:g.496A>G" "YP_009724389.1:p.Ser166Gly" "YP_009724389.1:Ser166Gly" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (132x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" -"Severe acute respiratory syndrome coronavirus 2" "NC_045512.2" "RefSeq" "798" "N178S" "NC_045512.2:g.533A>G" "YP_009724389.1:p.Asn178Ser" "YP_009724389.1:Asn178Ser" "open reading frame 1ab gene (SARS-CoV-2)" "orf1ab gene (SARS-CoV-2)" "open reading frame 1a polyprotein (SARS-CoV-2)" "Orf1a protein (SARS-CoV-2)" "frequency based fitness" "" "" "Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets)" "" "" "" "" "2023" "https://doi.org/10.1101/2023.01.30.526314" "doi:10.1101/2023.01.30.526314" "" "false" "Paul Gordon" "Pokay" From 99f27fc517d3087b9e1c11a804edde33588b090e Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 10:36:34 -0800 Subject: [PATCH 097/161] update Mpox workflow --- poxmvp_clinical_params.yaml | 13 +++++++++++ workflows/poxmvp.nf | 45 ++++++++++++++++++++----------------- 2 files changed, 37 insertions(+), 21 deletions(-) create mode 100644 poxmvp_clinical_params.yaml diff --git a/poxmvp_clinical_params.yaml b/poxmvp_clinical_params.yaml new file mode 100644 index 00000000..4c40c236 --- /dev/null +++ b/poxmvp_clinical_params.yaml @@ -0,0 +1,13 @@ +prefix: "poxmvp-2024-05-21" +mode: "reference" +grouping_criteria: "lineage" +skip_classification: true +skip_postprocessing: false +skip_posting: true +skip_harmonize: false +start_date: "2020-01-01" +end_date: "2024-05-21" +metadata_source: "ViralAi_EpiCoV" +metadata_config: "assets/metadata_conf/metadata.yaml" +outdir: "results/covidmvp" +mutation_indexfile: "results/covidmvp/covidmvp-2024-05-13/MUTATION_INDEX/2024-05-13.index.tsv" diff --git a/workflows/poxmvp.nf b/workflows/poxmvp.nf index 8d907af8..9d72d156 100644 --- a/workflows/poxmvp.nf +++ b/workflows/poxmvp.nf @@ -1,7 +1,6 @@ #!/usr/bin/env nextflow nextflow.enable.dsl = 2 - // include subworkflows include {PREPROCESSING } from '../subworkflows/local/virusmvp_preprocessing' include {VARIANT_CALLING } from '../subworkflows/local/virusmvp_variantcalling' @@ -9,7 +8,7 @@ include {ANNOTATION } from '../subworkflows/local/virusmvp_annot include {surveillance } from '../subworkflows/local/virusmvp_surveillance' include {GVF_PROCESSING_ANNOTATION } from '../subworkflows/local/virusmvp_gvf_processing_annotations' include {QUALITYCONTROL } from '../subworkflows/local/virusmvp_qc' -include {VIRALAI } from '../subworkflows/local/viralai_datadownload' +//include {VIRALAI } from '../subworkflows/local/viralai/viralai_datadownload' include {CLASSIFICATION } from '../subworkflows/local/virusmvp_classification' include {POSTPROCESSING } from '../subworkflows/local/virusmvp_postprocessing' @@ -27,17 +26,19 @@ workflow POXMVP { main: ch_voc = Channel.empty() + skip_variant_calling = false + seq = file(params.seq, checkIfExists: true) id = seq.getSimpleName() sequences = [ [ id:id ], seq ] - - if (params.mode == "reference"){ - meta = file(params.meta, checkIfExists: true) - id = meta.getSimpleName() - metadata = [ [ id:id ], meta ] + if (params.mode == "reference"){ + meta = file(params.meta, checkIfExists: true) + id = meta.getSimpleName() + metadata = [ [ id:id ], meta ] + if (!params.skip_harmonize){ config = file(params.metadata_config, checkIfExists: true) dataset = params.metadata_source @@ -47,7 +48,6 @@ workflow POXMVP { else{ metadata=metadata } - if (!params.skip_classification){ CLASSIFICATION(metadata, sequences) metadata=CLASSIFICATION.out.metadata @@ -77,29 +77,32 @@ workflow POXMVP { } } else{ - if(!params.skip_qc){ + if(seq.getExtension() == "vcf"){ + skip_variant_calling = true + annotation_vcf = [ [ id:seq.getBaseName() ], seq ] + ch_stats = [] + } + else{ + if(!params.skip_qc){ QUALITYCONTROL(sequences, sequences) sequences_grouped=QUALITYCONTROL.out.sequences_grouped ch_stats=QUALITYCONTROL.out.stats - } + } + } + } + if (!skip_variant_calling==true){ + VARIANT_CALLING(sequences_grouped, params.viral_genome, params.viral_genome_fai) + annotation_vcf=VARIANT_CALLING.out.vcf } - VARIANT_CALLING(sequences_grouped, params.viral_genome, params.viral_genome_fai) - annotation_vcf=VARIANT_CALLING.out.vcf ANNOTATION(annotation_vcf, ch_snpeff_db, ch_snpeff_config, params.viral_genome, ch_stats, ch_json) annotation_gvf=ANNOTATION.out.gvf GVF_PROCESSING_ANNOTATION(annotation_gvf) - + annotated_gvf = GVF_PROCESSING_ANNOTATION.out.annotation_gvf if(!params.skip_postprocessing){ - GVF_PROCESSING_ANNOTATION.out.annotation_gvf - .map { [it[1]] } - .collect() - .map { gvfs -> [ [id:"postprocessing"], gvfs ] } - .set { ch_collected_gvfs} - POSTPROCESSING(ch_collected_gvfs,PREPROCESSING.out.logfile) + POSTPROCESSING(annotated_gvf,PREPROCESSING.out.logfile) } - //surveillance(ch_gvf_surveillance, ch_variant, ch_stats, ch_surveillanceIndicators, ch_metadata ) - + //surveillance(ch_gvf_surveillance, ch_variant, ch_stats, ch_surveillanceIndicators, ch_metadata ) } \ No newline at end of file From e03e34a887a8ecd065e588afe1eb94339286b450 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 10:38:14 -0800 Subject: [PATCH 098/161] updated configuration workflow --- subworkflows/local/virusmvp_config.nf | 36 +++++++++++++-------------- 1 file changed, 18 insertions(+), 18 deletions(-) diff --git a/subworkflows/local/virusmvp_config.nf b/subworkflows/local/virusmvp_config.nf index 868a78e0..8ebec441 100644 --- a/subworkflows/local/virusmvp_config.nf +++ b/subworkflows/local/virusmvp_config.nf @@ -3,7 +3,7 @@ nextflow.enable.dsl = 2 // import modules -include { CONVERTGFFTOJSON } from '../../modules/local/convertgff2json' +//include { CONVERTGFFTOJSON } from '../../modules/local/convertgff2json' include { SNPEFF_BUILD } from '../../modules/local/snpeff_build' include { SAMTOOLS_FAIDX } from '../../modules/nf-core/samtools/faidx/main' @@ -11,27 +11,27 @@ include { SAMTOOLS_FAIDX } from '../../modules/nf-core/samtools/faidx workflow CONFIGURE_VIRUSMVP { take: - gff + //gff main: - ch_json = Channel.empty() + //ch_json = Channel.empty() ch_snpeff_db = Channel.empty() ch_snpeff_config = Channel.empty() ch_viral_fai = Channel.empty() - if (params.gene_color) { - color = file(params.gene_color, checkIfExists: true) - } else { - color = [] - } - if (params.gene_alias) { - alias = file(params.gene_alias, checkIfExists: true) - } else { - alias = [] - } - - CONVERTGFFTOJSON(gff, color, alias) - ch_json = CONVERTGFFTOJSON.out.json + // if (params.gene_color) { + // color = file(params.gene_color, checkIfExists: true) + // } else { + // color = [] + // } + // if (params.gene_alias) { + // alias = file(params.gene_alias, checkIfExists: true) + // } else { + // alias = [] + // } + + // CONVERTGFFTOJSON(gff, color, alias) + // ch_json = CONVERTGFFTOJSON.out.json SNPEFF_BUILD ( params.viral_genome, @@ -40,12 +40,12 @@ workflow CONFIGURE_VIRUSMVP { ch_snpeff_db = SNPEFF_BUILD.out.db ch_snpeff_config = SNPEFF_BUILD.out.config - + SAMTOOLS_FAIDX([[id: params.virus_accession_id], params.viral_genome], [[],[]]) ch_viral_fai=SAMTOOLS_FAIDX.out.fai emit: - ch_json + //ch_json ch_snpeff_db ch_snpeff_config ch_viral_fai From d01bd08fd7e73fcb6bc0e49f6d63dc94f5fed22f Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 10:39:20 -0800 Subject: [PATCH 099/161] updated configurations --- conf/eagle.config | 31 +++++++++++++++++++++++++++++++ conf/nf-ncov-voc.config | 4 ++-- conf/profiles.config | 3 +-- 3 files changed, 34 insertions(+), 4 deletions(-) create mode 100644 conf/eagle.config diff --git a/conf/eagle.config b/conf/eagle.config new file mode 100644 index 00000000..d321bca6 --- /dev/null +++ b/conf/eagle.config @@ -0,0 +1,31 @@ +/* +~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ + Nextflow config file for Eagle +~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ + Defines input files and everything required to run a fast and simple pipeline test. + + Use as follows: + nextflow run main.nf -profile eagle, --outdir + +---------------------------------------------------------------------------------------- +*/ + +params { + config_profile_name = 'eagle' + config_profile_description = 'eagle' + + // Define max resource allocations based on available compute resources on Eagle + max_cpus = 8 + max_memory = '12.GB' + max_time = '6.h' + +} + +process { + clusterOptions = { "--account=def-sponsor00" } + executor = 'slurm' +} + +executor { + queueSize = 12 +} diff --git a/conf/nf-ncov-voc.config b/conf/nf-ncov-voc.config index 25b2458d..a86823db 100644 --- a/conf/nf-ncov-voc.config +++ b/conf/nf-ncov-voc.config @@ -28,7 +28,7 @@ params { viral_gff = "$baseDir/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2.gff" mutation_indexfile = "$baseDir/assets/virus_mutation_index/NC_045512.2/mutation_index.tsv" config = "$baseDir/assets/config.ini" - gene_alias = "$baseDir/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json" + //gene_alias = "$baseDir/assets/virus_genomeAnnotation/NC_045512.2/NC_045512.2_key.json" /* ---------------------------------------------------------------------------- @@ -152,7 +152,7 @@ params { // problematic SARS-COV-2 sites probvcf = "$baseDir/assets/virus_problematicSites/NC_045512.2/problematic_sites_sarsCov2.vcf" - funcannot = "$baseDir/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v1.0.tsv" + funcannot = "$baseDir/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.1.tsv" skip_problematics_sites = false skip_peptide_annottaion = false genecoord = "$baseDir/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json" diff --git a/conf/profiles.config b/conf/profiles.config index abe07fa2..b7292ccc 100644 --- a/conf/profiles.config +++ b/conf/profiles.config @@ -64,6 +64,5 @@ profiles { executor.cpus = 16 executor.memory = 60.GB } - test { includeConfig 'conf/test.config' } - test_full { includeConfig 'conf/test_full.config' } + eagle { includeConfig 'eagle.config' } } \ No newline at end of file From 876879abebb2faed3df8dc62bcabfd724cd8e6b5 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 10:39:36 -0800 Subject: [PATCH 100/161] updated README --- README.md | 55 +++++++++++++++++++++++++++++++------------------------ 1 file changed, 31 insertions(+), 24 deletions(-) diff --git a/README.md b/README.md index 01621837..14fc8b08 100644 --- a/README.md +++ b/README.md @@ -7,19 +7,37 @@ ## Introduction -**nf-ncov-voc** is a bioinformatics analysis workflow used for -performing variant calling on SARS-CoV-2 genomes to identify and -profile mutations in Variants of Concern (VOCs), Variants of -Interest (VOIs) and Variants under Monitoring (VUMs). This workflow has -four main stages - **Preprocessing**, **Genomic Analysis (Variant -Calling)** , **Functional Annotation** and **Surveillance**. +**nf-ncov-voc** is a bioinformatics workflow developed to process viral genomes and integrate the contextual data. +The workflow was intially designed for processing SARS-CoV-2 for COVID-19 pandemic response and has been later adapted for more priority viruses e.g., Mpox and Influenza. The workflow is developed in a modular structure with several modules and sub-workflows leveraged from [nf-core](https://nf-co.re). These modules and sub-workflows are assembled in a plug-n-play manner based on the data and viral charatceristics. Each virus supported by the workflow has its own workflow file that directs the assembly of sub-workflows and modules. + +The workflow is built using [Nextflow](https://www.nextflow.io)- [DSL2](https://www.nextflow.io/docs/latest/dsl2.html), a workflow tool to run tasks across multiple compute infrastructures in a very portable manner. It can use `conda`/`Docker`/`Singularity` containers making installation trivial and results highly reproducible. + **nf-ncov-voc** workflow can be used in combination with an interactive -visualization tool [COVID-MVP](https://github.com/cidgoh/COVID-MVP) -or as a stand-alone high-throughput analysis tool to produce -mutation profiles and surveillance reports. +visualization tool [VIRUS-MVP](https://github.com/cidgoh/VIRUS-MVP) or as a stand-alone high-throughput analysis tool to produce mutation profiles and surveillance reports. + +A detailed structure and each module of the workflow is presented +below in the dataflow diagram + +### nf-ncov-voc Dataflow + +![DataFlow](figs/COVIDMVP.drawio.png) + +### Functional Annotation + +**nf-ncov-voc** offers a unique opportunity to integrate the contextual data with genomics data. Variant Called File (VCF) generated for each group or sample is then converted to a Genome Variant File (GVF) to integrate the functions associated to different mutations. For more information of how the functions are curated and structured see the dedicated repository [_Pokay_](https://github.com/nodrogluap/pokay) + +**nf-ncov-voc** with the help of functional data in _Pokay_, produces surveillance reports that are developed in collaboration with the Public Health partners and offers a high-level yet comprehensive report on each mutation its associated functions in literature. + +### Input data + +As an input, **nf-ncov-voc** can accept different formats, Whole Genome Sequences (WGS) in `FASTA` format with a Metadata file in `TSV` format; paired-end short read sequences in `FASTQ` format with a Metadata file in `TSV` format. Additionally, the input can also be `VCF` file that contains variants called. + +### Grouping data + +### Quality control + +### Variant Calling -As an input, **nf-ncov-voc** workflow requires SARS-CoV-2 consensus -sequences in `FASTA` format and Metadata file in `TSV` format. Sequences in pre-processing stage are filtered using Metadata variables, quality filtered and assigned lineages. Sequences assigned as VOCs, VOIs and VUMs are then mapped to SARS-CoV-2 genome, @@ -35,19 +53,6 @@ summarized using functional indicators to highlight key functions and mutations responsible for them for e.g. **P618H** role in _convalescent plasma escape_. -The workflow is built using [Nextflow](https://www.nextflow.io)- -[DSL2](https://www.nextflow.io/docs/latest/dsl2.html), a workflow -tool to run tasks across multiple compute infrastructures in a very -portable manner. It can use `conda`/`Docker`/`Singularity` -containers making installation trivial and results highly reproducible. - -A detailed structure and each module of the workflow is presented -below in the dataflow diagram - -### nf-ncov-voc Dataflow - -![DataFlow](figs/COVIDMVP.drawio.png) - ### Pre-Processing This module offers two ways to get lineage information for each @@ -121,6 +126,8 @@ See the [parameters](https://github.com/cidgoh/nf-ncov-voc/blob/master/docs/PARAMETERS.md) docs for all available options when running the workflow. +** Further developments will continue to adapt nf-ncov-voc to other viruses in near furture. ** + ## Usage 1. Install [`Nextflow`](https://www.nextflow.io/docs/latest/getstarted.html#installation) (`>=21.04.0`) From 25013e05dfa88afbefbb5929e0a626d487b54e82 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 10:50:41 -0800 Subject: [PATCH 101/161] updated SARS-CoV-2 workflow --- .../NC_045512.2/variants_classification.tsv | 2 +- covidmvp_clinical_params.yaml | 10 ++++------ 2 files changed, 5 insertions(+), 7 deletions(-) diff --git a/assets/virus_variants/NC_045512.2/variants_classification.tsv b/assets/virus_variants/NC_045512.2/variants_classification.tsv index 732623bc..28d6aaf7 100644 --- a/assets/virus_variants/NC_045512.2/variants_classification.tsv +++ b/assets/virus_variants/NC_045512.2/variants_classification.tsv @@ -11,4 +11,4 @@ Iota B.1.526 VOI 24-Mar-2021 n/a n/a de_escalated Kappa B.1.617.1 VOI 04-Apr-2021 n/a n/a de_escalated Lambda C.37 VOI 14-Jun-2021 n/a n/a de_escalated Mu B.1.621,BB.2 VOI 30-Aug-2021 n/a n/a de_escalated -Omicron B[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],C[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],D[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],E[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],F[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],G[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],H[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],J[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],K[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],L[A|B|C|D|E|F|G],X[E|G|H|J|K|L|M|N|P|Q|R|T|U|V|W|Y|Z|AC|AD|AE|AF|AG|AH|AJ|AK|AL|AM|AN|AP|AQ|AS|AT|AU|AV|AZ|BB|BD|BE|BF|BG|BH|BJ|BK|BL|BM|BN|BP|BQ|BR|BS|BT|BU|BV|BW|BY|BZ|CA|CB|CC|CD|CE|CF|CG|CH|CJ|CK|CL|CM|CN|CP|CQ|CR|CS|CT|CU|CV|CW|CY|CZ|DA|DB|DC|DD|DE|DF|DG|DH] VOC n/a 26-Nov-2021 24-Nov-2021 actively_circulating +Omicron B[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],C[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],D[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],E[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],F[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],G[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],H[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],J[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],K[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],L[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],M[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q|R|S|T|U|V|W|Y|Z],N[A|B|C|D|E|F|G|H|J|K|L|M|N|P|Q],X[E|G|H|J|K|L|M|N|P|Q|R|T|U|V|W|Y|Z|AC|AD|AE|AF|AG|AH|AJ|AK|AL|AM|AN|AP|AQ|AS|AT|AU|AV|AZ|BB|BD|BE|BF|BG|BH|BJ|BK|BL|BM|BN|BP|BQ|BR|BS|BT|BU|BV|BW|BY|BZ|CA|CB|CC|CD|CE|CF|CG|CH|CJ|CK|CL|CM|CN|CP|CQ|CR|CS|CT|CU|CV|CW|CY|CZ|DA|DB|DC|DD|DE|DF|DG|DH] VOC n/a 26-Nov-2021 24-Nov-2021 actively_circulating diff --git a/covidmvp_clinical_params.yaml b/covidmvp_clinical_params.yaml index 1c3a47b1..a0e22714 100644 --- a/covidmvp_clinical_params.yaml +++ b/covidmvp_clinical_params.yaml @@ -1,16 +1,14 @@ -prefix: "covidmvp-2024-05-21" mode: "reference" grouping_criteria: "lineage" viralai: true virusseq: true -virusseq_update: true +virusseq_update: false skip_classification: true skip_postprocessing: false skip_posting: true skip_harmonize: false start_date: "2020-01-01" -end_date: "2024-05-21" +end_date: "2024-10-25" metadata_source: "ViralAi_EpiCoV" -metadata_config: "assets/metadata_conf/metadata.yaml" -outdir: "results/covidmvp" -mutation_indexfile: "results/covidmvp/covidmvp-2024-05-13/MUTATION_INDEX/2024-05-13.index.tsv" +metadata_config: "/project/def-virusmvp/mzanwar/nf-ncov-voc/assets/metadata_conf/metadata.yaml" +outdir: "/project/def-virusmvp/mzanwar/nf-ncov-voc/results/covidmvp" From ca2de6a3373dfd3c839b55fa8038845cb29583cc Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 10:50:59 -0800 Subject: [PATCH 102/161] updated main workflow file --- main.nf | 45 +++++++++++++++------------------------------ 1 file changed, 15 insertions(+), 30 deletions(-) diff --git a/main.nf b/main.nf index 1afc23ba..4397b19b 100644 --- a/main.nf +++ b/main.nf @@ -7,7 +7,7 @@ script_files = "$baseDir/bin" // include workflows include { COVIDMVP } from './workflows/covidmvp' -//include { POXMVP } from './workflows/poxmvp' +include { POXMVP } from './workflows/poxmvp' include { WASTEWATER } from './workflows/virusmvp_wastewater' //include { FLUMVP } from './workflows/flumvp' @@ -20,7 +20,6 @@ include {cidgohHeader } from './modules/local/header' include {workflowHeader } from './modules/local/wf_header' - if (params.help){ log.info cidgohHeader() log.info workflowHeader() @@ -44,8 +43,6 @@ if ( !params.prefix ) { } } - - // main workflow workflow { main: @@ -60,22 +57,14 @@ workflow { } } - // Building configuration file for COVID-MVP - if(!params.skip_configuration){ - gff_file = file(params.viral_gff, checkIfExists: true) - gff = [ [ id:params.virus_accession_id ], gff_file ] - CONFIGURE_VIRUSMVP(gff) - ch_json=CONFIGURE_VIRUSMVP.out.ch_json - ch_snpeff_db=CONFIGURE_VIRUSMVP.out.ch_snpeff_db - ch_snpeff_config=CONFIGURE_VIRUSMVP.out.ch_snpeff_config - ch_viral_fai=CONFIGURE_VIRUSMVP.out.ch_viral_fai - } - else{ - ch_json = file(params.ch_json) - ch_snpeff_db = file(params.ch_snpeff_db) - ch_snpeff_config = file(params.ch_snpeff_config) - ch_viral_fai = file(params.ch_viral_fai) - } + CONFIGURE_VIRUSMVP() + json_file = file(params.genecoord, checkIfExists: true) + ch_json = [ [ id:params.virus_accession_id ], [ json_file ] ] + + ch_snpeff_db=CONFIGURE_VIRUSMVP.out.ch_snpeff_db + ch_snpeff_config=CONFIGURE_VIRUSMVP.out.ch_snpeff_config + ch_viral_fai=CONFIGURE_VIRUSMVP.out.ch_viral_fai + if (params.virus_accession_id = "NC_045512.2"){ println("Executing COVID-MVP") if (params.wastewater){ @@ -84,19 +73,15 @@ workflow { else{ COVIDMVP(ch_json, ch_snpeff_db, ch_snpeff_config, ch_viral_fai) } - - } else if (params.virus_accession_id = "NC_063383.1"){ println("Executing POX-MVP") - //POXMVP(ch_json, ch_snpeff_db, ch_snpeff_config, ch_viral_fai) - } - else { - println("Executing FLU-MVP") - //FLUMVP() + if (params.wastewater){ + WASTEWATER(ch_json, ch_snpeff_db, ch_snpeff_config, ch_viral_fai) + } + else{ + POXMVP(ch_json, ch_snpeff_db, ch_snpeff_config, ch_viral_fai) + } } - - - } From a9a67644226ee2da2a9f66ea5ad411ace4124bc4 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 10:51:39 -0800 Subject: [PATCH 103/161] updated ViralAi module --- modules/local/viralai/processViralai_metadata.nf | 1 - 1 file changed, 1 deletion(-) diff --git a/modules/local/viralai/processViralai_metadata.nf b/modules/local/viralai/processViralai_metadata.nf index 10a68722..bb4d1e1f 100644 --- a/modules/local/viralai/processViralai_metadata.nf +++ b/modules/local/viralai/processViralai_metadata.nf @@ -12,7 +12,6 @@ process PROCESS_VIRALAI_METADATA { output: tuple val(meta), path("*.csv.gz"), emit: gz - script: """ From fed4883a012f89e57cd9982bbb631887a6e7f46b Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 10:52:54 -0800 Subject: [PATCH 104/161] updated annotation sub-workflow --- subworkflows/local/virusmvp_annotation.nf | 6 +++--- 1 file changed, 3 insertions(+), 3 deletions(-) diff --git a/subworkflows/local/virusmvp_annotation.nf b/subworkflows/local/virusmvp_annotation.nf index 42107ebd..94c3203b 100644 --- a/subworkflows/local/virusmvp_annotation.nf +++ b/subworkflows/local/virusmvp_annotation.nf @@ -51,13 +51,13 @@ workflow ANNOTATION { //VCF to GVF transformation - if (ch_json == []){ + /*if (ch_json == []){ json_file = file(params.genecoord, checkIfExists: true) json = [ [ id:params.virus_accession_id ], [ json_file ] ] } else{ json = ch_json - } + }*/ threshold=0.75 if (params.wastewater){ lineage = [] @@ -79,7 +79,7 @@ workflow ANNOTATION { annotation_vcf, ch_stats, threshold, - json, + ch_json, lineage, wastewater_data, data_description, From 0637c473ab8b96e8a75ec2a4baf14a77c5777c77 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 10:53:11 -0800 Subject: [PATCH 105/161] updated ignored files --- .gitignore | 4 ++-- 1 file changed, 2 insertions(+), 2 deletions(-) diff --git a/.gitignore b/.gitignore index ac4c4b8d..beb9fbed 100644 --- a/.gitignore +++ b/.gitignore @@ -19,5 +19,5 @@ data/* hMPXV_* bin/web.log assets/config.ini -*-params.yaml -*.xz \ No newline at end of file +*.xz +*.log \ No newline at end of file From 6ff1b0c8d09efc8644664f6907edaca61a6a2c72 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 10:53:33 -0800 Subject: [PATCH 106/161] added vscode plugins --- .vscode/extensions.json | 3 +++ .vscode/settings.json | 7 +++++++ 2 files changed, 10 insertions(+) create mode 100644 .vscode/extensions.json create mode 100644 .vscode/settings.json diff --git a/.vscode/extensions.json b/.vscode/extensions.json new file mode 100644 index 00000000..2ba2749e --- /dev/null +++ b/.vscode/extensions.json @@ -0,0 +1,3 @@ +{ + "recommendations": ["nextflow.nextflow"] +} diff --git a/.vscode/settings.json b/.vscode/settings.json new file mode 100644 index 00000000..666a01db --- /dev/null +++ b/.vscode/settings.json @@ -0,0 +1,7 @@ +{ + "cSpell.words": [ + "bioinformatics" + ], + "nextflow.debug": true, + "nextflow.formatting.harshilAlignment": true +} From a0e9e1362dc8af93650fab18efde9453da6fedff Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 22:51:23 -0800 Subject: [PATCH 107/161] updated nextflow formatting --- bin/gvf2tsv.py | 3 +- conf/modules.config | 6 +- main.nf | 15 +- modules/local/addFunctionalAnnotation.nf | 29 +- modules/local/archive/custom.nf | 160 ++++++++ modules/local/archive/seqkit.nf | 20 +- modules/local/archive/seqkitstats.nf | 17 +- modules/local/archive/update_log_index.nf | 29 +- modules/local/convertgff2json.nf | 33 +- modules/local/custom.nf | 185 --------- modules/local/extractMetadata.nf | 32 +- modules/local/extractVariants.nf | 50 ++- modules/local/gvftoindexandlog.nf | 28 +- modules/local/mergeIndices.nf | 27 +- modules/local/mergeLogfiles.nf | 51 ++- modules/local/merge_classification_report.nf | 26 +- modules/local/post_log.nf | 19 +- modules/local/vcftogvf.nf | 60 ++- modules/local/viralai/viralai_multifasta.nf | 13 +- modules/nf-core/bwa/index/main.nf | 19 +- modules/nf-core/samtools/mpileup/main.nf | 22 +- modules/nf-core/samtools/view/main.nf | 63 ++-- subworkflows/local/virusmvp_classification.nf | 72 ++-- subworkflows/local/virusmvp_config.nf | 57 +-- subworkflows/local/virusmvp_preprocessing.nf | 109 +++--- subworkflows/local/virusmvp_qc.nf | 25 +- subworkflows/local/virusmvp_surveillance.nf | 30 +- subworkflows/local/virusmvp_variantcalling.nf | 111 +++--- workflows/covidmvp.nf | 186 +++++---- workflows/poxmvp.nf | 178 +++++---- workflows/virusmvp_wastewater.nf | 357 +++++++++--------- 31 files changed, 966 insertions(+), 1066 deletions(-) create mode 100644 modules/local/archive/custom.nf delete mode 100644 modules/local/custom.nf diff --git a/bin/gvf2tsv.py b/bin/gvf2tsv.py index ef1f2f1b..430fd26b 100755 --- a/bin/gvf2tsv.py +++ b/bin/gvf2tsv.py @@ -49,8 +49,7 @@ def gvf2tsv(gvf): df.columns = df.columns.str.replace("#", "") # drop unwanted columns - df = df.drop(labels=['seqid', 'type', 'end', - 'strand', 'score', 'phase', 'id'], axis=1) + df = df.drop(labels=['seqid', 'type', 'end', 'strand', 'score', 'phase', 'id'], axis=1) # rename 'dp' column to 'sequence_depth', make 'viral_lineage' # plural diff --git a/conf/modules.config b/conf/modules.config index fe67ccab..ab66e8ed 100644 --- a/conf/modules.config +++ b/conf/modules.config @@ -37,12 +37,12 @@ process { } - withName: COVIDMVP:QUALITYCONTROL:SEQKIT_STATS { + withName: SEQKIT_STATS { ext.args = "--all" ext.prefix = { "combined_stats" } } - withName: COVIDMVP:VARIANT_CALLING:MINIMAP2_ALIGN { + withName: MINIMAP2_ALIGN { ext.args = '-ax asm5' } @@ -56,7 +56,7 @@ process { mode: params.publish_dir_mode, saveAs: { filename -> filename.equals('versions.yml') ? null : filename } ] - ext.args = ext.args = "-p ${params.ploidy} \ + ext.args = "-p ${params.ploidy} \ -F ${params.var_MinFreqThreshold} \ -C 1 \ --min-coverage ${params.var_MinDepth} \ diff --git a/main.nf b/main.nf index 4397b19b..0cd773cd 100644 --- a/main.nf +++ b/main.nf @@ -51,11 +51,16 @@ workflow { log.info workflowHeader() if (!params.skip_permissions) { - allFiles = listOfFiles = file("$script_files/*") - for( def file : allFiles ) { - file.setPermissions('rwxr-x--x') - } - } + try { + def scriptFiles = file("$script_files/*") + scriptFiles.each { file -> + if (file.isFile()) { + file.setPermissions('rwxr-xr-x') // 755 in octal, more standard permissions + } + } + } catch (Exception e) { + log.warn "Unable to set permissions for files in $script_files: ${e.message}"} + } CONFIGURE_VIRUSMVP() json_file = file(params.genecoord, checkIfExists: true) diff --git a/modules/local/addFunctionalAnnotation.nf b/modules/local/addFunctionalAnnotation.nf index 9a269260..e0da9db4 100644 --- a/modules/local/addFunctionalAnnotation.nf +++ b/modules/local/addFunctionalAnnotation.nf @@ -1,30 +1,25 @@ process FUNCTIONALANNOTATION { - - tag "$meta.id" - + tag "${meta.id}" conda "conda-forge::pandas=1.4.3" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/pandas:1.4.3': - 'amancevice/pandas:1.4.3' }" - + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' + : 'amancevice/pandas:1.4.3'}" + input: - tuple val(meta), path(gvf) - tuple val(meta2), path(tsv) - + tuple val(meta), path(gvf) + tuple val(meta2), path(tsv) + output: - tuple val(meta), path("*.gvf"), emit: gvf + tuple val(meta), path("*.gvf"), emit: gvf script: - - def args = task.ext.args ?: '' def prefix = task.ext.prefix ?: "${meta.id}" """ addfunctions2gvf.py \\ - --ingvf $gvf \\ + --ingvf ${gvf} \\ --outgvf ${prefix}.annotated.gvf \\ - --functional_annotations $tsv + --functional_annotations ${tsv} """ - -} \ No newline at end of file +} diff --git a/modules/local/archive/custom.nf b/modules/local/archive/custom.nf new file mode 100644 index 00000000..16a42ece --- /dev/null +++ b/modules/local/archive/custom.nf @@ -0,0 +1,160 @@ +process virusseqMapLineage { + tag { "Mapping VirusSeq dataset to GISAID for lineages" } + publishDir "${params.outdir}/${params.prefix}/${task.process.replaceAll(":", "_")}", pattern: "*.tsv", mode: 'copy' + + input: + tuple val(meta), path(metadata) + tuple val(meta2), path(gisaid_metadata) + + output: + path ("VirusSeq_Mapped.tsv"), emit: mapped + + script: + """ + map_virusseq_GISAID.py --virusseq ${metadata} --gisaid ${gisaid_metadata} --output VirusSeq_Mapped.tsv + + """ +} + +process grabIndex { + tag { "grabing_SARS-CoV-2_index" } + + input: + path index_folder + + output: + file "*.fasta.*" + + script: + """ + ln -sf ${index_folder}/*.fasta.* ./ + """ +} + +process IVAR_VARIANTS_TO_VCF { + tag "${meta.id}" + conda "conda-forge::python=3.9.5 conda-forge::matplotlib=3.5.1 conda-forge::pandas=1.3.5 conda-forge::r-sys=3.4 conda-forge::regex=2021.11.10 conda-forge::scipy=1.7.3 conda-forge::biopython=1.79" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/mulled-v2-ff46c3f421ca930fcc54e67ab61c8e1bcbddfe22:1ad3da14f705eb0cdff6b5a44fea4909307524b4-0' + : 'quay.io/biocontainers/mulled-v2-ff46c3f421ca930fcc54e67ab61c8e1bcbddfe22:1ad3da14f705eb0cdff6b5a44fea4909307524b4-0'}" + + input: + tuple val(meta), path(tsv) + + output: + tuple val(meta), path("*.vcf"), emit: vcf + tuple val(meta), path("*.log"), emit: log + path "versions.yml", emit: versions + + when: + task.ext.when == null || task.ext.when + + script: + // This script is bundled with the pipeline, in nf-core/viralrecon/bin/ + def args = task.ext.args ?: '' + def prefix = task.ext.prefix ?: "${meta.id}" + """ + ivar_variants_to_vcf.py \\ + ${tsv} \\ + ${prefix}.vcf \\ + ${args} \\ + > ${prefix}.variant_counts.log + cat <<-END_VERSIONS > versions.yml + "${task.process}": + python: \$(python --version | sed 's/Python //g') + END_VERSIONS + """ +} + +process processGVCF { + tag "${meta.id}" + publishDir "${params.outdir}/${params.prefix}/${task.process.replaceAll(":", "_")}", pattern: "*variants.vcf", mode: 'copy' + + input: + tuple val(meta), path(gvcf) + + output: + tuple val(meta), path("*.vcf"), emit: vcf + tuple val(meta), path("*.log"), emit: log + path "versions.yml", emit: versions + + when: + gvcf.size() > 0 + + script: + """ + process_gvcf.py -d ${params.var_MinDepth} \ + -l ${params.lower_ambiguityFrequency} \ + -u ${params.upper_ambiguityFrequency} \ + -m ${gvcf.baseName}.mask.txt \ + -v ${gvcf.baseName}.variants.vcf \ + -c ${gvcf.baseName}.consensus.vcf ${gvcf} + """ +} + + +process surveillanceRawTsv { + tag { "Generating Raw Surveillance Data (TSV)" } + publishDir "${params.outdir}/${params.prefix}/${task.process.replaceAll(":", "_")}", pattern: "*.tsv", mode: 'copy' + + input: + path gvf + tuple path(variants), path(stats) + + output: + path ('*.tsv'), emit: surveillancetsv + + script: + if (params.mode == 'user') { + """ + gvf2tsv.py --gvf_files ${gvf} \ + --user + """ + } + else { + """ + gvf2tsv.py --gvf_files ${gvf} \ + --clades ${variants} \ + --table ${stats} \ + --all_variants + + """ + } +} + +process surveillancePDF { + tag { "Generating Surveillance reports PDF" } + publishDir "${params.outdir}/${params.prefix}/${task.process.replaceAll(":", "_")}", pattern: "*.pdf", mode: 'copy' + + input: + each tsv + path surveillanceindicators + path metadata + + output: + path ("*.pdf"), emit: surveillance_pdf + + script: + if (params.mode == 'reference') { + + """ + surveillance_report_pdf.py --tsv ${tsv} \ + --functions_table ${surveillanceindicators} \ + --metadata ${metadata} \ + --virusseq True > ${tsv.baseName}.tex + + tectonic -X compile ${tsv.baseName}.tex --reruns 3 --keep-intermediates --keep-logs + + + """ + } + else { + """ + surveillance_report_pdf.py --tsv ${tsv} \ + --functions_table ${surveillanceindicators} > ${tsv.baseName}.tex + + tectonic -X compile ${tsv.baseName}.tex --reruns 3 --keep-intermediates --keep-logs + + """ + } +} diff --git a/modules/local/archive/seqkit.nf b/modules/local/archive/seqkit.nf index 6dff724a..0e8c9462 100644 --- a/modules/local/archive/seqkit.nf +++ b/modules/local/archive/seqkit.nf @@ -1,18 +1,16 @@ process SEQKIT { - publishDir "${params.outdir}/${params.prefix}/${task.process.replaceAll(":","_")}", pattern: "*.fasta", mode: 'copy' + publishDir "${params.outdir}/${params.prefix}/${task.process.replaceAll(":", "_")}", pattern: "*.fasta", mode: 'copy' + tag { "${ids.Name}" } + label 'dev_env' - tag { "${ids.Name}" } + input: + tuple val(meta), path(ids) + tuple val(meta2), path(sequence) - label 'dev_env' + output: + tuple val(meta), path("*.fasta"), emit: fasta - input: - tuple val(meta), path(ids) - tuple val(meta), path(sequence) - - output: - tuple val(meta), path("*.fasta"), emit: fasta - - script: + script: """ seqkit grep -n -f ${ids} ${sequence} -j ${task.cpus} -o ${ids.baseName}.fasta -w 0 """ diff --git a/modules/local/archive/seqkitstats.nf b/modules/local/archive/seqkitstats.nf index 9e6dff10..edf72a42 100644 --- a/modules/local/archive/seqkitstats.nf +++ b/modules/local/archive/seqkitstats.nf @@ -1,20 +1,19 @@ process SEQKITSTATS { - tag "$meta.id" + tag "${meta.id}" label 'process_low' - conda "bioconda::seqkit=2.2.0" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/seqkit:2.2.0--h9ee0642_0': - 'biocontainers/seqkit:2.2.0--h9ee0642_0' }" - + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/seqkit:2.2.0--h9ee0642_0' + : 'biocontainers/seqkit:2.2.0--h9ee0642_0'}" + input: - path(samples) + tuple val(meta), path(samples) output: - path("samples_stats.tsv"), emit: stats + path ("samples_stats.tsv"), emit: stats script: - """ + """ seqkit stats ${samples} -o samples_stats.tsv """ diff --git a/modules/local/archive/update_log_index.nf b/modules/local/archive/update_log_index.nf index 8d99c8d0..d4e50927 100644 --- a/modules/local/archive/update_log_index.nf +++ b/modules/local/archive/update_log_index.nf @@ -1,26 +1,20 @@ process UPDATE_INDEX_LOG { - - tag "$meta.id" - + tag "${meta.id}" conda "conda-forge::pandas=1.4.3" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' : '' }" - + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' + : ''}" input: - tuple val(meta), path(gvfs) - tuple val(meta), path(log_file) - tuple val(meta), path(index) - + tuple val(meta), path(gvfs) + tuple val(meta2), path(log_file) + tuple val(meta3), path(index) + output: - tuple val(meta), path("*.tsv"), emit: tsv - tuple val(meta), path("*.log"), emit: log - + tuple val(meta), path("*.tsv"), emit: tsv + tuple val(meta), path("*.log"), emit: log script: - - def args = task.ext.args ?: '' - def prefix = task.ext.prefix ?: "${meta.id}" def log_date = "${params.end_date}" """ @@ -32,5 +26,4 @@ process UPDATE_INDEX_LOG { --log_savefile ${log_date}.log """ - -} \ No newline at end of file +} diff --git a/modules/local/convertgff2json.nf b/modules/local/convertgff2json.nf index b2319933..4dfa2a38 100644 --- a/modules/local/convertgff2json.nf +++ b/modules/local/convertgff2json.nf @@ -4,31 +4,30 @@ // Define the process to run process CONVERTGFFTOJSON { - tag "$meta.id" - + tag "${meta.id}" conda "conda-forge::pandas=1.4.3" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/pandas:1.4.3': - 'amancevice/pandas:1.4.3' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' + : 'amancevice/pandas:1.4.3'}" input: - tuple val(meta), path(gff) - path(color) - path(alias) - + tuple val(meta), path(gff) + path color + path alias + output: - tuple val(meta), path("*.json"), emit: json + tuple val(meta), path("*.json"), emit: json script: - def prefix = task.ext.prefix ?: "${meta.id}" - def color = color ? "--color_file ${color}" : '' - def alias = alias ? "--alias_file ${alias}" : '' - - """ + def prefix = task.ext.prefix ?: "${meta.id}" + def val_color = color ? "--color_file ${color}" : '' + def val_alias = alias ? "--alias_file ${alias}" : '' + + """ gff2json.py \\ --gff_file ${gff} \\ - $color \\ - $alias \\ + ${val_color} \\ + ${val_alias} \\ --json_file ${prefix}.json """ diff --git a/modules/local/custom.nf b/modules/local/custom.nf deleted file mode 100644 index f1c5f4ae..00000000 --- a/modules/local/custom.nf +++ /dev/null @@ -1,185 +0,0 @@ - - -/*process virusseqMapLineage{ - - tag {"Mapping VirusSeq dataset to GISAID for lineages"} - publishDir "${params.outdir}/${params.prefix}/${task.process.replaceAll(":","_")}", pattern: "*.tsv", mode: 'copy' - - input: - tuple val(meta), path(metadata) - tuple val(meta), path(gisaid_metadata) - - output: - path("VirusSeq_Mapped.tsv"), emit: mapped - - script: - """ - map_virusseq_GISAID.py --virusseq ${metadata} --gisaid ${gisaid_metadata} --output VirusSeq_Mapped.tsv - - """ -}*/ - - - - - -process grabIndex { - - tag { "grabing_SARS-CoV-2_index" } - - input: - path(index_folder) - - output: - file("*.fasta.*") - - script: - """ - ln -sf $index_folder/*.fasta.* ./ - """ -} - - - - -process IVAR_VARIANTS_TO_VCF { - tag "$meta.id" - - conda "conda-forge::python=3.9.5 conda-forge::matplotlib=3.5.1 conda-forge::pandas=1.3.5 conda-forge::r-sys=3.4 conda-forge::regex=2021.11.10 conda-forge::scipy=1.7.3 conda-forge::biopython=1.79" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/mulled-v2-ff46c3f421ca930fcc54e67ab61c8e1bcbddfe22:1ad3da14f705eb0cdff6b5a44fea4909307524b4-0' : - 'quay.io/biocontainers/mulled-v2-ff46c3f421ca930fcc54e67ab61c8e1bcbddfe22:1ad3da14f705eb0cdff6b5a44fea4909307524b4-0' }" - - input: - tuple val(meta), path(tsv) - - output: - tuple val(meta), path("*.vcf"), emit: vcf - tuple val(meta), path("*.log"), emit: log - path "versions.yml" , emit: versions - - when: - task.ext.when == null || task.ext.when - - script: // This script is bundled with the pipeline, in nf-core/viralrecon/bin/ - def args = task.ext.args ?: '' - def prefix = task.ext.prefix ?: "${meta.id}" - """ - ivar_variants_to_vcf.py \\ - $tsv \\ - ${prefix}.vcf \\ - $args \\ - > ${prefix}.variant_counts.log - cat <<-END_VERSIONS > versions.yml - "${task.process}": - python: \$(python --version | sed 's/Python //g') - END_VERSIONS - """ -} - -process processGVCF { - - tag {"${gvcf.baseName}"} - - publishDir "${params.outdir}/${params.prefix}/${task.process.replaceAll(":","_")}", pattern: "*variants.vcf", mode: 'copy' - - input: - path(gvcf) - - - output: - tuple val(meta), path("*.vcf"), emit: vcf - tuple val(meta), path("*.log"), emit: log - path "versions.yml" , emit: versions - - output: - path("*.variants.vcf"), emit: vcf - path("*.consensus.vcf") - path("*.txt") - - when: - gvcf.size()>0 - - script: - """ - process_gvcf.py -d ${params.var_MinDepth} \ - -l ${params.lower_ambiguityFrequency} \ - -u ${params.upper_ambiguityFrequency} \ - -m ${gvcf.baseName}.mask.txt \ - -v ${gvcf.baseName}.variants.vcf \ - -c ${gvcf.baseName}.consensus.vcf ${gvcf} - """ -} - - -process surveillanceRawTsv { - - tag {"Generating Raw Surveillance Data (TSV)"} - - publishDir "${params.outdir}/${params.prefix}/${task.process.replaceAll(":","_")}", pattern: "*.tsv", mode: 'copy' - - input: - path(gvf) - tuple(path(variants), path(stats)) - - output: - path ('*.tsv'), emit: surveillancetsv - - script: - if( params.mode == 'user' ){ - """ - gvf2tsv.py --gvf_files ${gvf} \ - --user - """ - } - else{ - """ - gvf2tsv.py --gvf_files ${gvf} \ - --clades ${variants} \ - --table ${stats} \ - --all_variants - - """ - } - - -} - -process surveillancePDF { - - tag {"Generating Surveillance reports PDF"} - - publishDir "${params.outdir}/${params.prefix}/${task.process.replaceAll(":","_")}", pattern: "*.pdf", mode: 'copy' - - input: - each tsv - path(surveillanceindicators) - path(metadata) - - output: - path("*.pdf"), emit: surveillance_pdf - - script: - if( params.mode == 'reference' ){ - - """ - surveillance_report_pdf.py --tsv ${tsv} \ - --functions_table ${surveillanceindicators} \ - --metadata ${metadata} \ - --virusseq True > ${tsv.baseName}.tex - - tectonic -X compile ${tsv.baseName}.tex --reruns 3 --keep-intermediates --keep-logs - - - """ - } - else{ - """ - surveillance_report_pdf.py --tsv ${tsv} \ - --functions_table ${surveillanceindicators} > ${tsv.baseName}.tex - - tectonic -X compile ${tsv.baseName}.tex --reruns 3 --keep-intermediates --keep-logs - - """ - } -} diff --git a/modules/local/extractMetadata.nf b/modules/local/extractMetadata.nf index f057a27b..69568909 100644 --- a/modules/local/extractMetadata.nf +++ b/modules/local/extractMetadata.nf @@ -1,30 +1,28 @@ process EXTRACTMETADATA { - tag "$meta.id" - + tag "${meta.id}" conda "conda-forge::pandas=1.4.3" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/pandas:1.4.3': - 'amancevice/pandas:1.4.3' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' + : 'amancevice/pandas:1.4.3'}" input: - tuple val(meta), path(metadata) - tuple val(meta2), val(x) - val time - + tuple val(meta), path(metadata) + tuple val(meta2), val(x) + val time + output: - - tuple val(meta2), path("*.tsv.gz"), emit: tsv - tuple val(meta2), path("*.txt"), emit: txt + tuple val(meta2), path("*.tsv.gz"), emit: tsv + tuple val(meta2), path("*.txt"), emit: txt script: - def prefix = task.ext.prefix ?: "${meta2.id}" - def time = time ? "--start_date ${params.start_date} --end_date ${params.end_date} " : '' - """ + def prefix = task.ext.prefix ?: "${meta2.id}" + def val_time = time ? "--start_date ${params.start_date} --end_date ${params.end_date} " : '' + """ extract_metadata.py \\ - $time \\ + ${val_time} \\ --group ${x} \\ --table ${metadata} \\ --outtable ${prefix}_metadata.tsv.gz \\ --outids ${prefix}.txt """ -} \ No newline at end of file +} diff --git a/modules/local/extractVariants.nf b/modules/local/extractVariants.nf index 92949c3f..b4baaeab 100644 --- a/modules/local/extractVariants.nf +++ b/modules/local/extractVariants.nf @@ -1,43 +1,41 @@ process EXTRACTVARIANTS { - tag "$meta.id" - + tag "${meta.id}" conda "conda-forge::pandas=1.4.3" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/pandas:1.4.3': - 'amancevice/pandas:1.4.3' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' + : 'amancevice/pandas:1.4.3'}" input: - tuple val(meta), path(variants) - tuple val(meta2), path(metadata) - val variant_file - val virusseq - val criteria - val variable - val time - + tuple val(meta), path(variants) + tuple val(meta2), path(metadata) + val variant_file + val virusseq + val criteria + val variable + val time + output: - tuple val(meta2), path("*.txt"), emit: txt - tuple val(meta2), path("*.log"), emit: log, optional: true + tuple val(meta2), path("*.txt"), emit: txt + tuple val(meta2), path("*.log"), emit: log, optional: true script: - def args = task.ext.args ?: '' def prefix = task.ext.prefix ?: "${meta2.id}" - def variant_file = variant_file ? "--variants $variants" : '' + def val_variant_file = variant_file ? "--variants ${variants}" : '' def virusseq_update = virusseq ? "--virusseq" : '' - def time = time ? "--start_date ${params.start_date} --end_date ${params.end_date}" : '' - def variable = variable ? "--variable ${params.variable}" : '' - def criteria = criteria ? "--criteria $criteria" : '' + def val_time = time ? "--start_date ${params.start_date} --end_date ${params.end_date}" : '' + def val_variable = variable ? "--variable ${params.variable}" : '' + def val_criteria = criteria ? "--criteria ${criteria}" : '' """ parse_variants.py \\ - $variant_file \\ - $virusseq_update \\ - $variable \\ - $time \\ - $criteria \\ + ${val_variant_file} \\ + ${virusseq_update} \\ + ${val_variable} \\ + ${val_time} \\ + ${val_criteria} \\ --metadata ${metadata} \\ --outfile ${prefix}_variants.txt \\ --logfile ${prefix}_web.log """ -} \ No newline at end of file +} diff --git a/modules/local/gvftoindexandlog.nf b/modules/local/gvftoindexandlog.nf index affe3412..2ec147dc 100644 --- a/modules/local/gvftoindexandlog.nf +++ b/modules/local/gvftoindexandlog.nf @@ -1,24 +1,18 @@ process GVF_TO_INDEX_LOG { - - tag "$meta.id" - + tag "${meta.id}" conda "conda-forge::dask=2023.10.1" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'biocontainers/dask:2023.10.1-py11-ol9_cv1' : - 'quay.io/biocontainers/dask:2023.10.1-py11-ol9_cv1' }" - + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'biocontainers/dask:2023.10.1-py11-ol9_cv1' + : 'quay.io/biocontainers/dask:2023.10.1-py11-ol9_cv1'}" input: - tuple val(meta), path(gvf) - + tuple val(meta), path(gvf) + output: - tuple val(meta), path("*.tsv"), emit: index - tuple val(meta), path("*.log"), emit: log - + tuple val(meta), path("*.tsv"), emit: index + tuple val(meta), path("*.log"), emit: log script: - - def args = task.ext.args ?: '' def prefix = task.ext.prefix ?: "${meta.id}" def end_date = "${params.end_date}" @@ -26,8 +20,6 @@ process GVF_TO_INDEX_LOG { gvf2indexandlog.py \\ --gvf_file ${gvf} \\ --index_savefile ${prefix}.${end_date}.index.tsv \\ - --log_savefile ${prefix}.${end_date}.log - + --log_savefile ${prefix}.${end_date}.log """ - -} \ No newline at end of file +} diff --git a/modules/local/mergeIndices.nf b/modules/local/mergeIndices.nf index a100ab72..0b46e0eb 100644 --- a/modules/local/mergeIndices.nf +++ b/modules/local/mergeIndices.nf @@ -1,32 +1,25 @@ process MERGE_INDICES { - - tag "$meta.id" - + tag "${meta.id}" conda "conda-forge::dask=2023.10.1" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'biocontainers/dask:2023.10.1-py11-ol9_cv1' : - 'quay.io/biocontainers/dask:2023.10.1-py11-ol9_cv1' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'biocontainers/dask:2023.10.1-py11-ol9_cv1' + : 'quay.io/biocontainers/dask:2023.10.1-py11-ol9_cv1'}" input: - tuple val(meta), path(index) - tuple val(meta2), path(previndex) - + tuple val(meta), path(index) + tuple val(meta2), path(previndex) + output: - tuple val(meta), path("*.tsv"), emit: updated_index + tuple val(meta), path("*.tsv"), emit: updated_index script: - - def args = task.ext.args ?: '' - def prefix = task.ext.prefix ?: "${meta.id}" def end_date = "${params.end_date}" def last_index = previndex ? "--original_index ${previndex}" : '' """ merge_indices.py \\ --gvf_indices ${index} \\ - $last_index \\ + ${last_index} \\ --index_savefile ${end_date}.index.tsv - """ - -} \ No newline at end of file +} diff --git a/modules/local/mergeLogfiles.nf b/modules/local/mergeLogfiles.nf index d5760400..0b66edf1 100644 --- a/modules/local/mergeLogfiles.nf +++ b/modules/local/mergeLogfiles.nf @@ -1,34 +1,25 @@ process MERGE_LOGFILES { +tag "${meta.id}" +conda "conda-forge::dask=2023.10.1" +container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container? +'biocontainers/dask:2023.10.1-py11-ol9_cv1': 'quay.io/biocontainers/dask:2023.10.1-py11-ol9_cv1'}" - tag "$meta.id" +input: +tuple val(meta), path(log_header) +tuple val(meta2), path(logs) +tuple val(meta3), path(index) - conda "conda-forge::dask=2023.10.1" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'biocontainers/dask:2023.10.1-py11-ol9_cv1' : - 'quay.io/biocontainers/dask:2023.10.1-py11-ol9_cv1' }" - +output: +tuple val(meta), path("*.tsv"), emit: merged_logfile - input: - tuple val(meta), path(log_header) - tuple val(meta2), path(logs) - tuple val(meta3), path(index) - - output: - tuple val(meta), path("*.tsv"), emit: merged_logfile - - script: - - def args = task.ext.args ?: '' - def prefix = task.ext.prefix ?: "${meta.id}" - def end_date = "${params.end_date}" - def last_index = index ? "--original_index ${index}" : '' - - """ - merge_logfiles.py \\ - --log_header ${log_header} \\ - --gvf_log ${logs} \\ - $last_index \\ - --log_savefile ${end_date}.log.tsv - """ - -} \ No newline at end of file +script: +def end_date = "${params.end_date}" +def last_index = index ? "--original_index ${index}" : '' +""" +merge_logfiles.py \\ +--log_header ${log_header} \\ +--gvf_log ${logs} \\ +${last_index} \\ +--log_savefile ${end_date}.log.tsv +""" +} diff --git a/modules/local/merge_classification_report.nf b/modules/local/merge_classification_report.nf index 403d3a4f..b40a2704 100644 --- a/modules/local/merge_classification_report.nf +++ b/modules/local/merge_classification_report.nf @@ -1,21 +1,19 @@ -process MERGE_CLASSIFFICATION_METADATA{ - tag "$meta.id" - +process MERGE_CLASSIFFICATION_METADATA { + tag "${meta.id}" conda "conda-forge::pandas=1.4.3" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/pandas:1.4.3': - 'amancevice/pandas:1.4.3' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' + : 'amancevice/pandas:1.4.3'}" input: - tuple val(meta), path(metadata) - tuple val(meta), path(classifier_report) + tuple val(meta), path(metadata) + tuple val(meta2), path(classifier_report) output: - tuple val(meta), path("Metadata_lineage.tsv"), emit: tsv + tuple val(meta), path("Metadata_lineage.tsv"), emit: tsv script: - """ - merge_classification_metadata.py --metadata ${metadata} --classifier ${pangolin_report} --output Metadata_lineage.tsv - - """ -} \ No newline at end of file + """ + merge_classification_metadata.py --metadata ${metadata} --classifier ${classifier_report} --output Metadata_lineage.tsv + """ +} diff --git a/modules/local/post_log.nf b/modules/local/post_log.nf index 97a1a72c..482e8af9 100644 --- a/modules/local/post_log.nf +++ b/modules/local/post_log.nf @@ -1,19 +1,15 @@ process POST_LOG { - - tag "$meta.id" - + tag "${meta.id}" conda "conda-forge::pandas=1.4.3" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/requests:2.26.0' : '' }" - + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/requests:2.26.0' + : ''}" input: - tuple val(meta), path(log_file) - path(config) + tuple val(meta), path(log_file) + path config script: - - def args = task.ext.args ?: '' def prefix = task.ext.prefix ?: "${meta.id}" def log_date = "${params.end_date}" @@ -25,5 +21,4 @@ process POST_LOG { -r ${config} """ - -} \ No newline at end of file +} diff --git a/modules/local/vcftogvf.nf b/modules/local/vcftogvf.nf index 9a7bac1e..4b8d25ee 100644 --- a/modules/local/vcftogvf.nf +++ b/modules/local/vcftogvf.nf @@ -1,46 +1,42 @@ process VCFTOGVF { - - tag "$meta.id" - + tag "${meta.id}" conda "conda-forge::pandas=1.4.3" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/pandas:1.4.3': - 'amancevice/pandas:1.4.3' }" - + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' + : 'amancevice/pandas:1.4.3'}" + input: - tuple val(meta), path(vcf) - path stats - val threshold - tuple val(meta2), path(json) - val lineage - val wastewater - val sampledesc - + tuple val(meta), path(vcf) + path stats + val threshold + tuple val(meta2), path(json) + val lineage + val wastewater + val sampledesc + output: - tuple val(meta), path("*.gvf"), emit: gvf + tuple val(meta), path("*.gvf"), emit: gvf script: def args = task.ext.args ?: '' def prefix = task.ext.prefix ?: "${meta.id}" def strain = lineage ? "--strain ${prefix}" : '' - def stat = stats ? "--size_stats ${stats}" : '' - def wastewater = wastewater ? "--wastewater" : '' - def group = "--sample_group ${meta.id}" - + def stat = stats ? "--size_stats ${stats}" : '' + def val_wastewater = wastewater ? "--wastewater" : '' + def group = "--sample_group ${meta.id}" """ - vcf2gvf.py --vcffile $vcf \\ - $stat \\ - --clades_threshold $threshold \\ - --gene_positions $json \\ - $wastewater \\ - $strain \\ - --sample_desc $sampledesc \\ - $group \\ - $args \\ - --outgvf ${prefix}.gvf + vcf2gvf.py --vcffile ${vcf} \\ + ${stat} \\ + --clades_threshold ${threshold} \\ + --gene_positions ${json} \\ + ${val_wastewater} \\ + ${strain} \\ + --sample_desc ${sampledesc} \\ + ${group} \\ + ${args} \\ + --outgvf ${prefix}.gvf """ - -} \ No newline at end of file +} diff --git a/modules/local/viralai/viralai_multifasta.nf b/modules/local/viralai/viralai_multifasta.nf index 1680cfaf..50b38f58 100644 --- a/modules/local/viralai/viralai_multifasta.nf +++ b/modules/local/viralai/viralai_multifasta.nf @@ -1,18 +1,17 @@ process DOWNLOAD_VIRALAI_MULTIFASTA { - - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'docker://cidgoh/virus-mvp-viralai:latest': '' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'docker://cidgoh/virus-mvp-viralai:latest' + : ''}" output: - path("*.xz"), emit: xz - + path ("*.xz"), emit: xz + + script: """ #!/usr/bin/env bash dnastack config set collections.url "${params.collections_api_url}" dnastack config set drs.url "${params.collections_drs_url}" dnastack collections query ${params.collection_slug_name} "SELECT * FROM viralai.${params.collection_slug_name}.files WHERE NAME LIKE 'CanCOGeN/multifasta_compressed/%' ORDER BY created_time DESC LIMIT 1" | jq -r '.[].drs_url' > test.txt dnastack files download -i test.txt - """ - } diff --git a/modules/nf-core/bwa/index/main.nf b/modules/nf-core/bwa/index/main.nf index 969f60b2..b369a07f 100644 --- a/modules/nf-core/bwa/index/main.nf +++ b/modules/nf-core/bwa/index/main.nf @@ -1,32 +1,31 @@ process BWA_INDEX { - tag "$fasta" + tag "${fasta}" label 'process_single' - conda "${moduleDir}/environment.yml" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/bwa:0.7.17--hed695b0_7' : - 'quay.io/biocontainers/bwa:0.7.17--hed695b0_7' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/bwa:0.7.17--hed695b0_7' + : 'quay.io/biocontainers/bwa:0.7.17--hed695b0_7'}" input: tuple val(meta), path(fasta) output: - tuple val(meta), path(bwa) , emit: index - path "versions.yml" , emit: versions + tuple val(meta), path(bwa), emit: index + path "versions.yml", emit: versions when: task.ext.when == null || task.ext.when script: def prefix = task.ext.prefix ?: "${fasta.baseName}" - def args = task.ext.args ?: '' + def args = task.ext.args ?: '' """ mkdir bwa bwa \\ index \\ - $args \\ + ${args} \\ -p bwa/${prefix} \\ - $fasta + ${fasta} cat <<-END_VERSIONS > versions.yml "${task.process}": diff --git a/modules/nf-core/samtools/mpileup/main.nf b/modules/nf-core/samtools/mpileup/main.nf index 24bc769e..370af10f 100644 --- a/modules/nf-core/samtools/mpileup/main.nf +++ b/modules/nf-core/samtools/mpileup/main.nf @@ -1,18 +1,18 @@ process SAMTOOLS_MPILEUP { - tag "$meta.id" + tag "${meta.id}" label 'process_single' - conda "${moduleDir}/environment.yml" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/samtools:1.19.2--h50ea8bc_0' : - 'quay.io/biocontainers/samtools:1.19.2--h50ea8bc_0' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/samtools:1.19.2--h50ea8bc_0' + : 'quay.io/biocontainers/samtools:1.19.2--h50ea8bc_0'}" + input: tuple val(meta), path(input), path(intervals) - path fasta + path fasta output: tuple val(meta), path("*.mpileup.gz"), emit: mpileup - path "versions.yml" , emit: versions + path "versions.yml", emit: versions when: task.ext.when == null || task.ext.when @@ -23,11 +23,11 @@ process SAMTOOLS_MPILEUP { def intervals = intervals ? "-l ${intervals}" : "" """ samtools mpileup \\ - --fasta-ref $fasta \\ + --fasta-ref ${fasta} \\ --output ${prefix}.mpileup \\ - $args \\ - $intervals \\ - $input + ${args} \\ + ${intervals} \\ + ${input} bgzip ${prefix}.mpileup cat <<-END_VERSIONS > versions.yml "${task.process}": diff --git a/modules/nf-core/samtools/view/main.nf b/modules/nf-core/samtools/view/main.nf index c326b894..eaed28fb 100644 --- a/modules/nf-core/samtools/view/main.nf +++ b/modules/nf-core/samtools/view/main.nf @@ -1,11 +1,10 @@ process SAMTOOLS_VIEW { - tag "$meta.id" + tag "${meta.id}" label 'process_low' - conda "${moduleDir}/environment.yml" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/samtools:1.19.2--h50ea8bc_0' : - 'quay.io/biocontainers/samtools:1.19.2--h50ea8bc_0' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/samtools:1.19.2--h50ea8bc_0' + : 'quay.io/biocontainers/samtools:1.19.2--h50ea8bc_0'}" input: tuple val(meta), path(input), path(index) @@ -13,13 +12,13 @@ process SAMTOOLS_VIEW { path qname output: - tuple val(meta), path("*.bam"), emit: bam, optional: true - tuple val(meta), path("*.cram"), emit: cram, optional: true - tuple val(meta), path("*.sam"), emit: sam, optional: true - tuple val(meta), path("*.bai"), emit: bai, optional: true - tuple val(meta), path("*.csi"), emit: csi, optional: true - tuple val(meta), path("*.crai"), emit: crai, optional: true - path "versions.yml", emit: versions + tuple val(meta), path("*.bam"), emit: bam, optional: true + tuple val(meta), path("*.cram"), emit: cram, optional: true + tuple val(meta), path("*.sam"), emit: sam, optional: true + tuple val(meta), path("*.bai"), emit: bai, optional: true + tuple val(meta), path("*.csi"), emit: csi, optional: true + tuple val(meta), path("*.crai"), emit: crai, optional: true + path "versions.yml", emit: versions when: task.ext.when == null || task.ext.when @@ -29,22 +28,27 @@ process SAMTOOLS_VIEW { def args2 = task.ext.args2 ?: '' def prefix = task.ext.prefix ?: "${meta.id}" def reference = fasta ? "--reference ${fasta}" : "" - def readnames = qname ? "--qname-file ${qname}": "" - def file_type = args.contains("--output-fmt sam") ? "sam" : - args.contains("--output-fmt bam") ? "bam" : - args.contains("--output-fmt cram") ? "cram" : - input.getExtension() - if ("$input" == "${prefix}.${file_type}") error "Input and output names are the same, use \"task.ext.prefix\" to disambiguate!" + def readnames = qname ? "--qname-file ${qname}" : "" + def file_type = args.contains("--output-fmt sam") + ? "sam" + : args.contains("--output-fmt bam") + ? "bam" + : args.contains("--output-fmt cram") + ? "cram" + : input.getExtension() + if ("${input}" == "${prefix}.${file_type}") { + error("Input and output names are the same, use \"task.ext.prefix\" to disambiguate!") + } """ samtools \\ view \\ - --threads ${task.cpus-1} \\ + --threads ${task.cpus - 1} \\ ${reference} \\ ${readnames} \\ - $args \\ + ${args} \\ -o ${prefix}.${file_type} \\ - $input \\ - $args2 + ${input} \\ + ${args2} cat <<-END_VERSIONS > versions.yml "${task.process}": @@ -55,11 +59,16 @@ process SAMTOOLS_VIEW { stub: def args = task.ext.args ?: '' def prefix = task.ext.prefix ?: "${meta.id}" - def file_type = args.contains("--output-fmt sam") ? "sam" : - args.contains("--output-fmt bam") ? "bam" : - args.contains("--output-fmt cram") ? "cram" : - input.getExtension() - if ("$input" == "${prefix}.${file_type}") error "Input and output names are the same, use \"task.ext.prefix\" to disambiguate!" + def file_type = args.contains("--output-fmt sam") + ? "sam" + : args.contains("--output-fmt bam") + ? "bam" + : args.contains("--output-fmt cram") + ? "cram" + : input.getExtension() + if ("${input}" == "${prefix}.${file_type}") { + error("Input and output names are the same, use \"task.ext.prefix\" to disambiguate!") + } def index = args.contains("--write-index") ? "touch ${prefix}.csi" : "" diff --git a/subworkflows/local/virusmvp_classification.nf b/subworkflows/local/virusmvp_classification.nf index f6b85f7c..d64f8b8f 100644 --- a/subworkflows/local/virusmvp_classification.nf +++ b/subworkflows/local/virusmvp_classification.nf @@ -5,53 +5,49 @@ nextflow.enable.dsl = 2 // Check input samplesheet and get read channels // -include { PANGOLIN } from '../../modules/nf-core/pangolin' +include { PANGOLIN } from '../../modules/nf-core/pangolin' include { MERGE_CLASSIFFICATION_METADATA } from '../../modules/local/merge_classification_report' -include { NEXTCLADE_RUN } from '../../modules/nf-core/nextclade/run' -include { NEXTCLADE_DATASETGET } from '../../modules/nf-core/nextclade/datasetget' +include { NEXTCLADE_RUN } from '../../modules/nf-core/nextclade/run' +include { NEXTCLADE_DATASETGET } from '../../modules/nf-core/nextclade/datasetget' // Define the workflow -workflow CLASSIFICATION{ - +workflow CLASSIFICATION { take: - metadata - sequences + metadata + sequences main: - - // Run pangolin - if (!params.skip_pangolin){ - PANGOLIN( sequences ) - pangolin_report = PANGOLIN.out.report - if (metadata != 'NO_FILE'){ - MERGE_PANGOLIN_METADATA(metadata, pangolin_report) - metadata = MERGE_PANGOLIN_METADATA.out.tsv - merged_metadata = metadata - } + + // Run pangolin + if (!params.skip_pangolin) { + PANGOLIN(sequences) + pangolin_report = PANGOLIN.out.report + if (metadata != 'NO_FILE') { + MERGE_CLASSIFFICATION_METADATA(metadata, pangolin_report) + metadata = MERGE_CLASSIFFICATION_METADATA.out.tsv + merged_metadata = metadata + } + } + + // RUN NEXTCLADE + if (!params.skip_nextclade) { + if (params.virus_accession_id == "NC_045512.2") { + dataset = 'sars-cov-2' + reference = 'MN908947' + tag = '2021-06-01T12:00:00Z' + } + else if (params.virus_accession_id == "NC_063383.1") { + dataset = "hMPXV" + reference = "NC_063383.1" + tag = "2023-08-01T12:00:00Z" } - - // RUN NEXTCLADE - if (!params.skip_nextclade){ - if (params.virus_accession_id == "NC_045512.2"){ - dataset = 'sars-cov-2' - reference = 'MN908947' - tag = '2021-06-01T12:00:00Z' - } - else if(params.virus_accession_id == "NC_063383.1"){ - dataset = "hMPXV" - reference = "NC_063383.1" - tag = "2023-08-01T12:00:00Z" - } - NEXTCLADE_DATASETGET ( dataset, reference, tag ) - NEXTCLADE_RUN ( sequences, NEXTCLADE_DATASETGET.out.dataset ) - //metadata = MERGE_PANGOLIN_METADATA(metadata, PANGOLIN.out.report) - //merged_metadata = metadata - } - merged_metadata = metadata + NEXTCLADE_DATASETGET(dataset, reference, tag) + NEXTCLADE_RUN(sequences, NEXTCLADE_DATASETGET.out.dataset) + } + merged_metadata = metadata emit: - merged_metadata - sequences + merged_metadata } diff --git a/subworkflows/local/virusmvp_config.nf b/subworkflows/local/virusmvp_config.nf index 8ebec441..ad3d0668 100644 --- a/subworkflows/local/virusmvp_config.nf +++ b/subworkflows/local/virusmvp_config.nf @@ -4,49 +4,28 @@ nextflow.enable.dsl = 2 // import modules //include { CONVERTGFFTOJSON } from '../../modules/local/convertgff2json' -include { SNPEFF_BUILD } from '../../modules/local/snpeff_build' -include { SAMTOOLS_FAIDX } from '../../modules/nf-core/samtools/faidx/main' - +include { SNPEFF_BUILD } from '../../modules/local/snpeff_build' +include { SAMTOOLS_FAIDX } from '../../modules/nf-core/samtools/faidx/main' workflow CONFIGURE_VIRUSMVP { - - take: - //gff - main: - //ch_json = Channel.empty() - ch_snpeff_db = Channel.empty() - ch_snpeff_config = Channel.empty() - ch_viral_fai = Channel.empty() + ch_snpeff_db = Channel.empty() + ch_snpeff_config = Channel.empty() + ch_viral_fai = Channel.empty() + + SNPEFF_BUILD( + params.viral_genome, + params.viral_gbk + ) + + ch_snpeff_db = SNPEFF_BUILD.out.db + ch_snpeff_config = SNPEFF_BUILD.out.config - // if (params.gene_color) { - // color = file(params.gene_color, checkIfExists: true) - // } else { - // color = [] - // } - // if (params.gene_alias) { - // alias = file(params.gene_alias, checkIfExists: true) - // } else { - // alias = [] - // } - - // CONVERTGFFTOJSON(gff, color, alias) - // ch_json = CONVERTGFFTOJSON.out.json - - SNPEFF_BUILD ( - params.viral_genome, - params.viral_gbk - ) + SAMTOOLS_FAIDX([[id: params.virus_accession_id], params.viral_genome], [[], []]) + ch_viral_fai = SAMTOOLS_FAIDX.out.fai - ch_snpeff_db = SNPEFF_BUILD.out.db - ch_snpeff_config = SNPEFF_BUILD.out.config - - SAMTOOLS_FAIDX([[id: params.virus_accession_id], params.viral_genome], [[],[]]) - ch_viral_fai=SAMTOOLS_FAIDX.out.fai - emit: - //ch_json - ch_snpeff_db - ch_snpeff_config - ch_viral_fai + ch_snpeff_db + ch_snpeff_config + ch_viral_fai } diff --git a/subworkflows/local/virusmvp_preprocessing.nf b/subworkflows/local/virusmvp_preprocessing.nf index fef04539..18791a96 100644 --- a/subworkflows/local/virusmvp_preprocessing.nf +++ b/subworkflows/local/virusmvp_preprocessing.nf @@ -3,69 +3,68 @@ nextflow.enable.dsl = 2 // import modules -include { EXTRACTVARIANTS } from '../../modules/local/extractVariants' -include { EXTRACTMETADATA } from '../../modules/local/extractMetadata' -include { SEQKIT_GREP } from '../../modules/nf-core/seqkit/grep/main' +include { EXTRACTVARIANTS } from '../../modules/local/extractVariants' +include { EXTRACTMETADATA } from '../../modules/local/extractMetadata' +include { SEQKIT_GREP } from '../../modules/nf-core/seqkit/grep/main' workflow PREPROCESSING { take: - metadata - sequences - + metadata + sequences main: - variant = file(params.variant, checkIfExists: true) - variants = [ [ id:params.virus_accession_id ], variant ] - - - if(params.virusseq_update){ - virusseq=true - } - else{ - virusseq=false - } + variant = file(params.variant, checkIfExists: true) + variants = [[id: params.virus_accession_id], variant] + + + if (params.virusseq_update) { + virusseq = true + } + else { + virusseq = false + } + + if (params.skip_variantparsing) { + variantfile = [] + } + else { + variantfile = true + } + + if (params.variable) { + variable = params.variable + } + else { + variable = [] + } + + criteria = Channel.of(params.grouping_criteria) + EXTRACTVARIANTS(variants, metadata, variantfile, virusseq, criteria, variable, true) + + EXTRACTVARIANTS.out.txt + .splitText() + .map { id, voc -> tuple([[id: voc.tokenize(':')[1].replaceAll(" ", "_").trim()], voc.replaceAll(" ", "_").trim()]) } + .set { ch_group } + - if(params.skip_variantparsing){ - variantfile = [] - } - else{ - variantfile = true - } + if (EXTRACTVARIANTS.out.log) { + logfile = EXTRACTVARIANTS.out.log + } + EXTRACTMETADATA(metadata, ch_group, true) - if(params.variable){ - variable = params.variable - } - else{ - variable = [] - } + if (params.grouping_criteria == "time") { + ids_channel = EXTRACTMETADATA.out.txt.map { it -> it[1] }.flatten() + ids_channel.view() + } + else { + ids = EXTRACTMETADATA.out.txt + ids_channel = ids.map { it[1] } + } + SEQKIT_GREP(sequences, ids_channel) - criteria = Channel.of(params.grouping_criteria) - EXTRACTVARIANTS(variants, metadata, variantfile, virusseq, criteria, variable, time=true) - - EXTRACTVARIANTS.out.txt - .splitText() - .map{id, voc -> tuple([[id:voc.tokenize(':')[1].replaceAll(" ", "_").trim()], voc.replaceAll(" ", "_").trim()])} - .set{ ch_group } - - - if(EXTRACTVARIANTS.out.log){ - logfile = EXTRACTVARIANTS.out.log - } - EXTRACTMETADATA(metadata, ch_group, time=true) - - if (params.grouping_criteria == "time"){ - ids_channel = EXTRACTMETADATA.out.txt.map {it-> it[1]} .flatten() - ids_channel.view() - } - else{ - ids = EXTRACTMETADATA.out.txt - ids_channel = ids.map{it[1]} - } - SEQKIT_GREP(sequences, ids_channel) - emit: - metadata = EXTRACTMETADATA.out.tsv - sequences = SEQKIT_GREP.out.filter - logfile = logfile + metadata = EXTRACTMETADATA.out.tsv + sequences = SEQKIT_GREP.out.filter + logfile = logfile } diff --git a/subworkflows/local/virusmvp_qc.nf b/subworkflows/local/virusmvp_qc.nf index 076fab5e..6e1b4227 100644 --- a/subworkflows/local/virusmvp_qc.nf +++ b/subworkflows/local/virusmvp_qc.nf @@ -3,24 +3,19 @@ nextflow.enable.dsl = 2 // import modules - - -include { BBMAP } from '../../modules/local/bbmap_reformat' -include { SEQKIT_STATS } from '../../modules/nf-core/seqkit/stats/main' - - +include { BBMAP } from '../../modules/local/bbmap_reformat' +include { SEQKIT_STATS } from '../../modules/nf-core/seqkit/stats/main' workflow QUALITYCONTROL { - take: - sequences_grouped - ch_collected_sequences + take: + sequences_grouped + ch_collected_sequences main: - BBMAP(sequences_grouped) - SEQKIT_STATS(ch_collected_sequences) - - emit: - sequences_grouped = BBMAP.out.fasta - stats = SEQKIT_STATS.out.stats + BBMAP(sequences_grouped) + SEQKIT_STATS(ch_collected_sequences) + emit: + sequences_grouped = BBMAP.out.fasta + stats = SEQKIT_STATS.out.stats } diff --git a/subworkflows/local/virusmvp_surveillance.nf b/subworkflows/local/virusmvp_surveillance.nf index 95074c18..c2abb9c6 100644 --- a/subworkflows/local/virusmvp_surveillance.nf +++ b/subworkflows/local/virusmvp_surveillance.nf @@ -4,24 +4,22 @@ nextflow.enable.dsl = 2 // import modules -include { surveillanceRawTsv } from '../../modules/local/custom' -include { surveillancePDF } from '../../modules/local/custom' - +include { surveillanceRawTsv } from '../../modules/local/archive/custom' +include { surveillancePDF } from '../../modules/local/archive/custom' workflow surveillance { - take: - ch_gvf - ch_variant - ch_stats - ch_surveillanceIndicators - ch_metadata + take: + ch_gvf + ch_variant + ch_stats + ch_surveillanceIndicators + ch_metadata - main: - surveillanceRawTsv(ch_gvf, ch_variant.combine(ch_stats)) - surveillancePDF(surveillanceRawTsv.out.surveillancetsv.flatten(), ch_surveillanceIndicators, ch_metadata) - ch_surv=surveillancePDF.out.surveillance_pdf - - emit: - ch_surv + main: + surveillanceRawTsv(ch_gvf, ch_variant.combine(ch_stats)) + surveillancePDF(surveillanceRawTsv.out.surveillancetsv.flatten(), ch_surveillanceIndicators, ch_metadata) + ch_surv = surveillancePDF.out.surveillance_pdf + emit: + ch_surv } diff --git a/subworkflows/local/virusmvp_variantcalling.nf b/subworkflows/local/virusmvp_variantcalling.nf index 842bd142..0b45954f 100644 --- a/subworkflows/local/virusmvp_variantcalling.nf +++ b/subworkflows/local/virusmvp_variantcalling.nf @@ -3,77 +3,70 @@ nextflow.enable.dsl = 2 // import modules -include { IVAR } from '../../modules/local/ivar' -//include { tsvTovcf } from '../modules/local/custom' -include { BWA_INDEX } from '../../modules/nf-core/bwa/index/main' -include { BWA_MEM } from '../../modules/nf-core/bwa/mem/main' -include { MINIMAP2_ALIGN } from '../../modules/nf-core/minimap2/align/main' -include { GUNZIP } from '../../modules/nf-core/gunzip/main' -include { TABIX_BGZIPTABIX } from '../../modules/nf-core/tabix/bgziptabix/main' -include { BCFTOOLS_NORM } from '../../modules/nf-core/bcftools/norm/main' +include { IVAR } from '../../modules/local/ivar' +include { IVAR_VARIANTS_TO_VCF } from '../../modules/local/archive/custom' +include { BWA_INDEX } from '../../modules/nf-core/bwa/index/main' +include { BWA_MEM } from '../../modules/nf-core/bwa/mem/main' +include { MINIMAP2_ALIGN } from '../../modules/nf-core/minimap2/align/main' +include { GUNZIP } from '../../modules/nf-core/gunzip/main' +include { TABIX_BGZIPTABIX } from '../../modules/nf-core/tabix/bgziptabix/main' +include { BCFTOOLS_NORM } from '../../modules/nf-core/bcftools/norm/main' // import sub-workflows -include { BAM_VARIANT_CALLING_SORT_FREEBAYES_BCFTOOLS } from '../nf-core/bam_variant_calling_sort_freebayes_bcftools/main' -include { BAM_SORT_STATS_SAMTOOLS } from '../nf-core/bam_sort_stats_samtools/main' +include { BAM_VARIANT_CALLING_SORT_FREEBAYES_BCFTOOLS } from '../nf-core/bam_variant_calling_sort_freebayes_bcftools/main' +include { BAM_SORT_STATS_SAMTOOLS } from '../nf-core/bam_sort_stats_samtools/main' workflow VARIANT_CALLING { take: - sequences_grouped - viral_genome - viral_genome_fai + sequences_grouped + viral_genome + viral_genome_fai main: - - fasta = Channel.value([[params.virus_accession_id], file(viral_genome, checkIfExists: true)]) - - if (params.viral_aligner == "bwa"){ - BWA_INDEX([[id: params.virus_accession_id], viral_genome]) - // BWA_MEM(sequences_grouped, BWA_INDEX.out.index, false ) - // bam=BWA_MEM.out.bam - } - else{ - MINIMAP2_ALIGN(sequences_grouped, [[id: params.virus_accession_id], viral_genome], true, false, false) - bam=MINIMAP2_ALIGN.out.bam - } - - BAM_SORT_STATS_SAMTOOLS(bam,fasta) - sorted_bam=BAM_SORT_STATS_SAMTOOLS.out.bam - bam_index=BAM_SORT_STATS_SAMTOOLS.out.bai - bam_bai = bam_index.join(sorted_bam).map{meta, bai, bam -> [meta, bam, bai, [] , [] , [] ]} - - if(params.ivar){ - IVAR(ch_bam.combine(ch_ref).combine(ch_refgff)) - tsvTovcf(IVAR.out.variants) - //ch_vcf=tsvTovcf.out.vcf - } - else{ - - genome =Channel.value([[id : params.virus_accession_id], - file(viral_genome, checkIfExists: true), - file(viral_genome_fai, checkIfExists: true) - ]) - BAM_VARIANT_CALLING_SORT_FREEBAYES_BCFTOOLS(bam_bai , genome , [[],[]], [[],[]], [[],[]] ) - GUNZIP(BAM_VARIANT_CALLING_SORT_FREEBAYES_BCFTOOLS.out.vcf) - } + fasta = Channel.value([[params.virus_accession_id], file(viral_genome, checkIfExists: true)]) - TABIX_BGZIPTABIX( - GUNZIP.out.gunzip - ) + if (params.viral_aligner == "bwa") { + BWA_INDEX([[id: params.virus_accession_id], viral_genome]) + } + else { + MINIMAP2_ALIGN(sequences_grouped, [[id: params.virus_accession_id], viral_genome], true, false, false) + ch_bam = MINIMAP2_ALIGN.out.bam + } + + BAM_SORT_STATS_SAMTOOLS(ch_bam, fasta) + sorted_bam = BAM_SORT_STATS_SAMTOOLS.out.bam + bam_index = BAM_SORT_STATS_SAMTOOLS.out.bai + bam_bai = bam_index.join(sorted_bam).map { meta, bai, bam -> [meta, bam, bai, [], [], []] } - BCFTOOLS_NORM( - TABIX_BGZIPTABIX.out.gz_tbi, - [[id: params.virus_accession_id], viral_genome] + if (params.ivar) { + IVAR(ch_bam.combine(viral_genome).combine(params.ch_refgff)) + IVAR_VARIANTS_TO_VCF(IVAR.out.variants) + } + else { + + genome = Channel.value( + [ + [id: params.virus_accession_id], + file(viral_genome, checkIfExists: true), + file(viral_genome_fai, checkIfExists: true) + ] ) - vcf=BCFTOOLS_NORM.out.vcf - + BAM_VARIANT_CALLING_SORT_FREEBAYES_BCFTOOLS(bam_bai, genome, [[], []], [[], []], [[], []]) + GUNZIP(BAM_VARIANT_CALLING_SORT_FREEBAYES_BCFTOOLS.out.vcf) + } - emit: - vcf - - + TABIX_BGZIPTABIX( + GUNZIP.out.gunzip + ) -} + BCFTOOLS_NORM( + TABIX_BGZIPTABIX.out.gz_tbi, + [[id: params.virus_accession_id], viral_genome] + ) + vcf = BCFTOOLS_NORM.out.vcf - \ No newline at end of file + emit: + vcf +} diff --git a/workflows/covidmvp.nf b/workflows/covidmvp.nf index 1bb8709e..83276dd9 100644 --- a/workflows/covidmvp.nf +++ b/workflows/covidmvp.nf @@ -2,114 +2,108 @@ nextflow.enable.dsl = 2 // include subworkflows -include {PREPROCESSING } from '../subworkflows/local/virusmvp_preprocessing' -include {VARIANT_CALLING } from '../subworkflows/local/virusmvp_variantcalling' -include {ANNOTATION } from '../subworkflows/local/virusmvp_annotation' -include {surveillance } from '../subworkflows/local/virusmvp_surveillance' -include {GVF_PROCESSING_ANNOTATION } from '../subworkflows/local/virusmvp_gvf_processing_annotations' -include {QUALITYCONTROL } from '../subworkflows/local/virusmvp_qc' -include {VIRALAI } from '../subworkflows/local/viralai/viralai_datadownload' -include {CLASSIFICATION } from '../subworkflows/local/virusmvp_classification' -include {POSTPROCESSING } from '../subworkflows/local/virusmvp_postprocessing' +include { PREPROCESSING } from '../subworkflows/local/virusmvp_preprocessing' +include { VARIANT_CALLING } from '../subworkflows/local/virusmvp_variantcalling' +include { ANNOTATION } from '../subworkflows/local/virusmvp_annotation' +include { surveillance } from '../subworkflows/local/virusmvp_surveillance' +include { GVF_PROCESSING_ANNOTATION } from '../subworkflows/local/virusmvp_gvf_processing_annotations' +include { QUALITYCONTROL } from '../subworkflows/local/virusmvp_qc' +include { VIRALAI } from '../subworkflows/local/viralai/viralai_datadownload' +include { CLASSIFICATION } from '../subworkflows/local/virusmvp_classification' +include { POSTPROCESSING } from '../subworkflows/local/virusmvp_postprocessing' // include modules include { METADATA_HARMONIZER } from '../modules/local/harmonize_metadata' workflow COVIDMVP { - take: - ch_json - ch_snpeff_db - ch_snpeff_config - ch_viral_fai - - main: - ch_voc = Channel.empty() - skip_variant_calling = false - if(params.viralai){ - VIRALAI() - metadata=VIRALAI.out.meta - sequences=VIRALAI.out.seq + ch_json + ch_snpeff_db + ch_snpeff_config + + main: + //ch_voc = Channel.empty() + skip_variant_calling = false + if (params.viralai) { + VIRALAI() + metadata = VIRALAI.out.meta + sequences = VIRALAI.out.seq + } + else { + seq = file(params.seq, checkIfExists: true) + id = seq.getSimpleName() + sequences = [[id: id], seq] + } + + if (params.mode == "reference") { + if (!params.viralai) { + meta = file(params.meta, checkIfExists: true) + id = meta.getSimpleName() + metadata = [[id: id], meta] + } + + if (!params.skip_harmonize) { + config = file(params.metadata_config, checkIfExists: true) + dataset = params.metadata_source + METADATA_HARMONIZER(metadata, config, dataset) + metadata = METADATA_HARMONIZER.out.gz } - else{ - seq = file(params.seq, checkIfExists: true) - id = seq.getSimpleName() - sequences = [ [ id:id ], seq ] + else { + metadata = metadata + } + if (!params.skip_classification) { + CLASSIFICATION(metadata, sequences) + metadata = CLASSIFICATION.out.metadata } - if (params.mode == "reference"){ - if (!params.viralai){ - meta = file(params.meta, checkIfExists: true) - id = meta.getSimpleName() - metadata = [ [ id:id ], meta ] - } - - if (!params.skip_harmonize){ - config = file(params.metadata_config, checkIfExists: true) - dataset = params.metadata_source - METADATA_HARMONIZER(metadata, config, dataset) - metadata=METADATA_HARMONIZER.out.gz - } - else{ - metadata=metadata - } - if (!params.skip_classification){ - CLASSIFICATION(metadata, sequences) - metadata=CLASSIFICATION.out.metadata - sequences=CLASSIFICATION.out.sequences - } - PREPROCESSING(metadata, sequences) - - metadata =PREPROCESSING.out.metadata - sequences=PREPROCESSING.out.sequences - - sequences - .map { key, fasta_files -> - tuple( [[id:fasta_files.getBaseName(2)], [fasta_files]] ) - } - .set{sequences_grouped} - - sequences - .map { [it[1]] } - .collect() - .map { sequences -> [ [id:"seqkit_stat"], sequences ] } - .set { ch_collected_sequences} - - if(!params.skip_qc){ - QUALITYCONTROL(sequences_grouped, ch_collected_sequences) - sequences_grouped=QUALITYCONTROL.out.sequences_grouped - ch_stats=QUALITYCONTROL.out.stats + PREPROCESSING(metadata, sequences) + metadata = PREPROCESSING.out.metadata + sequences = PREPROCESSING.out.sequences + + sequences + .map { fasta_files -> + tuple([[id: fasta_files.getBaseName(2)], [fasta_files]]) } + .set { sequences_grouped } + + sequences + .map { [it[1]] } + .collect() + .map { sequences -> [[id: "seqkit_stat"], sequences] } + .set { ch_collected_sequences } + + if (!params.skip_qc) { + QUALITYCONTROL(sequences_grouped, ch_collected_sequences) + sequences_grouped = QUALITYCONTROL.out.sequences_grouped + ch_stats = QUALITYCONTROL.out.stats } - else{ - if(seq.getExtension() == "vcf"){ - skip_variant_calling = true - annotation_vcf = [ [ id:seq.getBaseName() ], seq ] - ch_stats = [] - } - else{ - if(!params.skip_qc){ - QUALITYCONTROL(sequences, sequences) - sequences_grouped=QUALITYCONTROL.out.sequences_grouped - ch_stats=QUALITYCONTROL.out.stats - } - } + } + else { + if (seq.getExtension() == "vcf") { + skip_variant_calling = true + annotation_vcf = [[id: seq.getBaseName()], seq] + ch_stats = [] } - if (!skip_variant_calling==true){ - VARIANT_CALLING(sequences_grouped, params.viral_genome, params.viral_genome_fai) - annotation_vcf=VARIANT_CALLING.out.vcf + else { + if (!params.skip_qc) { + QUALITYCONTROL(sequences, sequences) + sequences_grouped = QUALITYCONTROL.out.sequences_grouped + ch_stats = QUALITYCONTROL.out.stats + } } - - ANNOTATION(annotation_vcf, ch_snpeff_db, ch_snpeff_config, params.viral_genome, ch_stats, ch_json) - annotation_gvf=ANNOTATION.out.gvf + } + if (!skip_variant_calling == true) { + VARIANT_CALLING(sequences_grouped, params.viral_genome, params.viral_genome_fai) + annotation_vcf = VARIANT_CALLING.out.vcf + } - GVF_PROCESSING_ANNOTATION(annotation_gvf) - annotated_gvf = GVF_PROCESSING_ANNOTATION.out.annotation_gvf - if(!params.skip_postprocessing){ - POSTPROCESSING(annotated_gvf,PREPROCESSING.out.logfile) - } - - //surveillance(ch_gvf_surveillance, ch_variant, ch_stats, ch_surveillanceIndicators, ch_metadata ) - -} \ No newline at end of file + ANNOTATION(annotation_vcf, ch_snpeff_db, ch_snpeff_config, params.viral_genome, ch_stats, ch_json) + annotation_gvf = ANNOTATION.out.gvf + + GVF_PROCESSING_ANNOTATION(annotation_gvf) + annotated_gvf = GVF_PROCESSING_ANNOTATION.out.annotation_gvf + if (!params.skip_postprocessing) { + POSTPROCESSING(annotated_gvf, PREPROCESSING.out.logfile) + } +} diff --git a/workflows/poxmvp.nf b/workflows/poxmvp.nf index 9d72d156..a7d16e0a 100644 --- a/workflows/poxmvp.nf +++ b/workflows/poxmvp.nf @@ -2,107 +2,103 @@ nextflow.enable.dsl = 2 // include subworkflows -include {PREPROCESSING } from '../subworkflows/local/virusmvp_preprocessing' -include {VARIANT_CALLING } from '../subworkflows/local/virusmvp_variantcalling' -include {ANNOTATION } from '../subworkflows/local/virusmvp_annotation' -include {surveillance } from '../subworkflows/local/virusmvp_surveillance' -include {GVF_PROCESSING_ANNOTATION } from '../subworkflows/local/virusmvp_gvf_processing_annotations' -include {QUALITYCONTROL } from '../subworkflows/local/virusmvp_qc' +include { PREPROCESSING } from '../subworkflows/local/virusmvp_preprocessing' +include { VARIANT_CALLING } from '../subworkflows/local/virusmvp_variantcalling' +include { ANNOTATION } from '../subworkflows/local/virusmvp_annotation' +include { surveillance } from '../subworkflows/local/virusmvp_surveillance' +include { GVF_PROCESSING_ANNOTATION } from '../subworkflows/local/virusmvp_gvf_processing_annotations' +include { QUALITYCONTROL } from '../subworkflows/local/virusmvp_qc' //include {VIRALAI } from '../subworkflows/local/viralai/viralai_datadownload' -include {CLASSIFICATION } from '../subworkflows/local/virusmvp_classification' -include {POSTPROCESSING } from '../subworkflows/local/virusmvp_postprocessing' +include { CLASSIFICATION } from '../subworkflows/local/virusmvp_classification' +include { POSTPROCESSING } from '../subworkflows/local/virusmvp_postprocessing' // include modules include { METADATA_HARMONIZER } from '../modules/local/harmonize_metadata' workflow POXMVP { - take: - ch_json - ch_snpeff_db - ch_snpeff_config - ch_viral_fai - - main: - ch_voc = Channel.empty() - skip_variant_calling = false - - - seq = file(params.seq, checkIfExists: true) - id = seq.getSimpleName() - sequences = [ [ id:id ], seq ] - - - if (params.mode == "reference"){ - meta = file(params.meta, checkIfExists: true) - id = meta.getSimpleName() - metadata = [ [ id:id ], meta ] - - if (!params.skip_harmonize){ - config = file(params.metadata_config, checkIfExists: true) - dataset = params.metadata_source - METADATA_HARMONIZER(metadata, config, dataset) - metadata=METADATA_HARMONIZER.out.gz - } - else{ - metadata=metadata - } - if (!params.skip_classification){ - CLASSIFICATION(metadata, sequences) - metadata=CLASSIFICATION.out.metadata - sequences=CLASSIFICATION.out.sequences - } - PREPROCESSING(metadata, sequences) - - metadata =PREPROCESSING.out.metadata - sequences=PREPROCESSING.out.sequences - - sequences - .map { key, fasta_files -> - tuple( [[id:fasta_files.getBaseName(2)], [fasta_files]] ) - } - .set{sequences_grouped} - - sequences - .map { [it[1]] } - .collect() - .map { sequences -> [ [id:"seqkit_stat"], sequences ] } - .set { ch_collected_sequences} - - if(!params.skip_qc){ - QUALITYCONTROL(sequences_grouped, ch_collected_sequences) - sequences_grouped=QUALITYCONTROL.out.sequences_grouped - ch_stats=QUALITYCONTROL.out.stats - } + ch_json + ch_snpeff_db + ch_snpeff_config + + main: + //ch_voc = Channel.empty() + skip_variant_calling = false + + + seq = file(params.seq, checkIfExists: true) + id = seq.getSimpleName() + sequences = [[id: id], seq] + + + if (params.mode == "reference") { + meta = file(params.meta, checkIfExists: true) + id = meta.getSimpleName() + metadata = [[id: id], meta] + + if (!params.skip_harmonize) { + config = file(params.metadata_config, checkIfExists: true) + dataset = params.metadata_source + METADATA_HARMONIZER(metadata, config, dataset) + metadata = METADATA_HARMONIZER.out.gz } - else{ - if(seq.getExtension() == "vcf"){ - skip_variant_calling = true - annotation_vcf = [ [ id:seq.getBaseName() ], seq ] - ch_stats = [] + else { + metadata = metadata + } + if (!params.skip_classification) { + CLASSIFICATION(metadata, sequences) + metadata = CLASSIFICATION.out.metadata + sequences = CLASSIFICATION.out.sequences + } + PREPROCESSING(metadata, sequences) + + metadata = PREPROCESSING.out.metadata + sequences = PREPROCESSING.out.sequences + + sequences + .map { key, fasta_files -> + tuple([[id: fasta_files.getBaseName(2)], [fasta_files]]) } - else{ - if(!params.skip_qc){ - QUALITYCONTROL(sequences, sequences) - sequences_grouped=QUALITYCONTROL.out.sequences_grouped - ch_stats=QUALITYCONTROL.out.stats - } - } + .set { sequences_grouped } + + sequences + .map { [it[1]] } + .collect() + .map { sequences -> [[id: "seqkit_stat"], sequences] } + .set { ch_collected_sequences } + + if (!params.skip_qc) { + QUALITYCONTROL(sequences_grouped, ch_collected_sequences) + sequences_grouped = QUALITYCONTROL.out.sequences_grouped + ch_stats = QUALITYCONTROL.out.stats } - if (!skip_variant_calling==true){ - VARIANT_CALLING(sequences_grouped, params.viral_genome, params.viral_genome_fai) - annotation_vcf=VARIANT_CALLING.out.vcf + } + else { + if (seq.getExtension() == "vcf") { + skip_variant_calling = true + annotation_vcf = [[id: seq.getBaseName()], seq] + ch_stats = [] } - - ANNOTATION(annotation_vcf, ch_snpeff_db, ch_snpeff_config, params.viral_genome, ch_stats, ch_json) - annotation_gvf=ANNOTATION.out.gvf - - GVF_PROCESSING_ANNOTATION(annotation_gvf) - annotated_gvf = GVF_PROCESSING_ANNOTATION.out.annotation_gvf - if(!params.skip_postprocessing){ - POSTPROCESSING(annotated_gvf,PREPROCESSING.out.logfile) + else { + if (!params.skip_qc) { + QUALITYCONTROL(sequences, sequences) + sequences_grouped = QUALITYCONTROL.out.sequences_grouped + ch_stats = QUALITYCONTROL.out.stats + } } - - //surveillance(ch_gvf_surveillance, ch_variant, ch_stats, ch_surveillanceIndicators, ch_metadata ) -} \ No newline at end of file + } + if (!skip_variant_calling == true) { + VARIANT_CALLING(sequences_grouped, params.viral_genome, params.viral_genome_fai) + annotation_vcf = VARIANT_CALLING.out.vcf + } + + ANNOTATION(annotation_vcf, ch_snpeff_db, ch_snpeff_config, params.viral_genome, ch_stats, ch_json) + annotation_gvf = ANNOTATION.out.gvf + + GVF_PROCESSING_ANNOTATION(annotation_gvf) + annotated_gvf = GVF_PROCESSING_ANNOTATION.out.annotation_gvf + if (!params.skip_postprocessing) { + POSTPROCESSING(annotated_gvf, PREPROCESSING.out.logfile) + } +} diff --git a/workflows/virusmvp_wastewater.nf b/workflows/virusmvp_wastewater.nf index 34e44cec..54edea88 100644 --- a/workflows/virusmvp_wastewater.nf +++ b/workflows/virusmvp_wastewater.nf @@ -1,195 +1,214 @@ // Importing the modules required for the sub-workflow -include { FASTP as WW_FASTP } from '../modules/nf-core/fastp/main' -include { SEQKIT_STATS as WW_SEQKIT_STATS } from '../modules/nf-core/seqkit/stats/main' -include { MINIMAP2_ALIGN as MINIMAP2_ALIGN_HOST } from '../modules/nf-core/minimap2/align/main' -include { MINIMAP2_ALIGN as MINIMAP2_ALIGN_VIRAL } from '../modules/nf-core/minimap2/align/main' -include { BWA_INDEX as WW_BWA_INDEX_HOST } from '../modules/nf-core/bwa/index/main' -include { BWA_INDEX as WW_BWA_INDEX_VIRAL } from '../modules/nf-core/bwa/index/main' -include { SAMTOOLS_INDEX as WW_SAMTOOLS_INDEX_HOST } from '../modules/nf-core/samtools/index/main' -include { SAMTOOLS_INDEX as WW_SAMTOOLS_INDEX_VIRAL } from '../modules/nf-core/samtools/index/main' -include { BWA_MEM as WW_BWA_MEM_HOST } from '../modules/nf-core/bwa/mem/main' -include { BWA_MEM as WW_BWA_MEM_VIRAL } from '../modules/nf-core/bwa/mem/main' -include { SAMTOOLS_FLAGSTAT as WW_SAMTOOLS_FLAGSTAT_HOST } from '../modules/nf-core/samtools/flagstat/main' -include { SAMTOOLS_FLAGSTAT as WW_SAMTOOLS_FLAGSTAT_VIRAL } from '../modules/nf-core/samtools/flagstat/main' -include { SAMTOOLS_VIEW as WW_SAMTOOLS_VIEW } from '../modules/nf-core/samtools/view/main' -include { SAMTOOLS_FASTQ as WW_SAMTOOLS_FASTQ } from '../modules/nf-core/samtools/fastq/main' -include { SAMTOOLS_SORT as WW_SAMTOOLS_SORT } from '../modules/nf-core/samtools/sort/main' +include { FASTP as WW_FASTP } from '../modules/nf-core/fastp/main' +include { SEQKIT_STATS as WW_SEQKIT_STATS } from '../modules/nf-core/seqkit/stats/main' +include { MINIMAP2_ALIGN as MINIMAP2_ALIGN_HOST } from '../modules/nf-core/minimap2/align/main' +include { MINIMAP2_ALIGN as MINIMAP2_ALIGN_VIRAL } from '../modules/nf-core/minimap2/align/main' +include { BWA_INDEX as WW_BWA_INDEX_HOST } from '../modules/nf-core/bwa/index/main' +include { BWA_INDEX as WW_BWA_INDEX_VIRAL } from '../modules/nf-core/bwa/index/main' +include { SAMTOOLS_INDEX as WW_SAMTOOLS_INDEX_HOST } from '../modules/nf-core/samtools/index/main' +include { SAMTOOLS_INDEX as WW_SAMTOOLS_INDEX_VIRAL } from '../modules/nf-core/samtools/index/main' +include { BWA_MEM as WW_BWA_MEM_HOST } from '../modules/nf-core/bwa/mem/main' +include { BWA_MEM as WW_BWA_MEM_VIRAL } from '../modules/nf-core/bwa/mem/main' +include { SAMTOOLS_FLAGSTAT as WW_SAMTOOLS_FLAGSTAT_HOST } from '../modules/nf-core/samtools/flagstat/main' +include { SAMTOOLS_FLAGSTAT as WW_SAMTOOLS_FLAGSTAT_VIRAL } from '../modules/nf-core/samtools/flagstat/main' +include { SAMTOOLS_VIEW as WW_SAMTOOLS_VIEW } from '../modules/nf-core/samtools/view/main' +include { SAMTOOLS_FASTQ as WW_SAMTOOLS_FASTQ } from '../modules/nf-core/samtools/fastq/main' +include { SAMTOOLS_SORT as WW_SAMTOOLS_SORT } from '../modules/nf-core/samtools/sort/main' //include { SAMTOOLS_INDEX as WW_SAMTOOLS_INDEX_IVAR } from '../../modules/nf-core/samtools/index/main' -include { articDownloadScheme } from '../modules/local/arcticdownloadscheme' -include { IVAR_TRIM as WW_IVAR_TRIM } from '../modules/nf-core/ivar/trim/main' -include { FREEBAYES as WW_FREEBAYES } from '../modules/nf-core/freebayes/main' -include { SNPEFF_BUILD } from '../modules/local/snpeff_build' -include { SAMTOOLS_FAIDX } from '../modules/nf-core/samtools/faidx/main' -include { SAMTOOLS_MPILEUP as WW_SAMTOOLS_MPILEUP } from '../modules/nf-core/samtools/mpileup/main' -include { FREYJA_UPDATE } from '../modules/nf-core/freyja/update/main' -include { FREYJA_DEMIX } from '../modules/nf-core/freyja/demix/main' -include { FREYJA_VARIANTS } from '../modules/nf-core/freyja/variants/main' -include { IVAR_VARIANTS_TO_VCF as WW_IVAR_VARIANTS_TO_VCF } from '../modules/local/custom' -include { XZ_DECOMPRESS } from '../modules/nf-core/xz/decompress/main' - -include {INPUT_CHECK } from '../subworkflows/local/input_check' -include { BAM_VARIANT_DEMIX_BOOT_FREYJA } from '../subworkflows/nf-core/bam_variant_demix_boot_freyja/main' -include { ANNOTATION } from '../subworkflows/local/virusmvp_annotation' -include { GVF_PROCESSING_ANNOTATION } from '../subworkflows/local/virusmvp_gvf_processing_annotations' +include { articDownloadScheme } from '../modules/local/arcticdownloadscheme' +include { IVAR_TRIM as WW_IVAR_TRIM } from '../modules/nf-core/ivar/trim/main' +include { FREEBAYES as WW_FREEBAYES } from '../modules/nf-core/freebayes/main' +include { SNPEFF_BUILD } from '../modules/local/snpeff_build' +include { SAMTOOLS_FAIDX } from '../modules/nf-core/samtools/faidx/main' +include { SAMTOOLS_MPILEUP as WW_SAMTOOLS_MPILEUP } from '../modules/nf-core/samtools/mpileup/main' +include { FREYJA_UPDATE } from '../modules/nf-core/freyja/update/main' +include { FREYJA_DEMIX } from '../modules/nf-core/freyja/demix/main' +include { FREYJA_VARIANTS } from '../modules/nf-core/freyja/variants/main' +include { IVAR_VARIANTS_TO_VCF as WW_IVAR_VARIANTS_TO_VCF } from '../modules/local/archive/custom' +include { XZ_DECOMPRESS } from '../modules/nf-core/xz/decompress/main' + +include { INPUT_CHECK } from '../subworkflows/local/input_check' +include { BAM_VARIANT_DEMIX_BOOT_FREYJA } from '../subworkflows/nf-core/bam_variant_demix_boot_freyja/main' +include { ANNOTATION } from '../subworkflows/local/virusmvp_annotation' +include { GVF_PROCESSING_ANNOTATION } from '../subworkflows/local/virusmvp_gvf_processing_annotations' workflow WASTEWATER { - take: - ch_json - ch_snpeff_db - ch_snpeff_config - ch_viral_fai + ch_json + ch_snpeff_db + ch_snpeff_config main: - ch_short_reads = Channel.empty() - if (params.input) { ch_input = file(params.input) } else { exit 1, 'Input samplesheet not specified!' } - ch_versions = Channel.empty() - INPUT_CHECK ( - ch_input - ) - ch_short_reads=INPUT_CHECK.out.reads - - - ch_voc = Channel.empty() - ch_versions = Channel.empty() - articDownloadScheme() - if (!params.skip_fastp) { - if (params.adapter_fasta) { adapter = file(params.adapter_fasta) - WW_FASTP ( - ch_short_reads, adapter, params.save_trimmed_fail, params.save_merged - ) - } - else{ - WW_FASTP ( - ch_short_reads, [], params.save_trimmed_fail, params.save_merged - ) - } - ch_short_reads = WW_FASTP.out.reads - ch_versions = ch_versions.mix(WW_FASTP.out.versions) + ch_short_reads = Channel.empty() + if (params.input) { + ch_input = file(params.input) + } + else { + exit(1, 'Input samplesheet not specified!') + } + ch_versions = Channel.empty() + INPUT_CHECK( + ch_input + ) + ch_short_reads = INPUT_CHECK.out.reads + + + //ch_voc = Channel.empty() + ch_versions = Channel.empty() + articDownloadScheme() + if (!params.skip_fastp) { + if (params.adapter_fasta) { + adapter = file(params.adapter_fasta) + WW_FASTP( + ch_short_reads, + adapter, + params.save_trimmed_fail, + params.save_merged + ) } - - WW_SEQKIT_STATS(ch_short_reads) - human_genome = [ - [ id:params.host_genome_id, single_end:true ], // meta map - file(params.host_genome, checkIfExists: true) - ] - viral_genome = [ - [ id:params.viral_genome_id, single_end:true ], // meta map - file(params.viral_genome, checkIfExists: true) - ] - if (!params.skip_dehosting){ - if (params.dehost_aligner=='bwa') { - XZ_DECOMPRESS(human_genome) - human_genome = XZ_DECOMPRESS.out.file - WW_BWA_INDEX_HOST(human_genome) - human_genome_index = WW_BWA_INDEX_HOST.out.index - reads = ch_short_reads - sorted=params.bwa_sort_bam - WW_BWA_MEM_HOST( - reads, - human_genome_index, - human_genome, - sorted - ) - ch_mapped_bam=WW_BWA_MEM_HOST.out.bam - } - else { - - reads = ch_short_reads - bam_format = params.bam_format //true - cigar_paf_format = params.cigar_paf_format //false - cigar_bam = params.cigar_bam //false - MINIMAP2_ALIGN_HOST ( - reads, - human_genome, - bam_format, - cigar_paf_format, - cigar_bam - ) - ch_mapped_bam=MINIMAP2_ALIGN_HOST.out.bam - } - - WW_SAMTOOLS_INDEX_HOST ( - ch_mapped_bam - ) - bam_index = WW_SAMTOOLS_INDEX_HOST.out.bai - - WW_SAMTOOLS_FLAGSTAT_HOST ( - ch_mapped_bam.combine ( - bam_index, by: 0 - ) - ) - - WW_SAMTOOLS_VIEW( - ch_mapped_bam.combine(bam_index, by: 0), - [[],[]], - []) - interleaved=params.interleaved - WW_SAMTOOLS_FASTQ( - WW_SAMTOOLS_VIEW.out.bam, interleaved) - - ch_short_reads = WW_SAMTOOLS_FASTQ.out.fastq + else { + WW_FASTP( + ch_short_reads, + [], + params.save_trimmed_fail, + params.save_merged + ) } - - if (params.viral_aligner=='bwa') { - WW_BWA_INDEX_VIRAL(viral_genome) - viral_genome_index = WW_BWA_INDEX_VIRAL.out.index + ch_short_reads = WW_FASTP.out.reads + ch_versions = ch_versions.mix(WW_FASTP.out.versions) + } + + WW_SEQKIT_STATS(ch_short_reads) + human_genome = [ + [id: params.host_genome_id, single_end: true], + file(params.host_genome, checkIfExists: true) + ] + viral_genome = [ + [id: params.viral_genome_id, single_end: true], + file(params.viral_genome, checkIfExists: true) + ] + if (!params.skip_dehosting) { + if (params.dehost_aligner == 'bwa') { + XZ_DECOMPRESS(human_genome) + human_genome = XZ_DECOMPRESS.out.file + WW_BWA_INDEX_HOST(human_genome) + human_genome_index = WW_BWA_INDEX_HOST.out.index reads = ch_short_reads - sorted=params.bwa_sort_bam - WW_BWA_MEM_VIRAL( + sorted = params.bwa_sort_bam + WW_BWA_MEM_HOST( reads, - viral_genome_index, - viral_genome, + human_genome_index, + human_genome, sorted ) - ch_viral_bam=WW_BWA_MEM_VIRAL.out.bam + ch_mapped_bam = WW_BWA_MEM_HOST.out.bam } else { - + reads = ch_short_reads - bam_format = params.bam_format //true - cigar_paf_format = params.cigar_paf_format //false - cigar_bam = params.cigar_bam //false - MINIMAP2_ALIGN_VIRAL ( - reads, - viral_genome, - bam_format, - cigar_paf_format, - cigar_bam + bam_format = params.bam_format + //true + cigar_paf_format = params.cigar_paf_format + //false + cigar_bam = params.cigar_bam + //false + MINIMAP2_ALIGN_HOST( + reads, + human_genome, + bam_format, + cigar_paf_format, + cigar_bam ) - ch_viral_bam=MINIMAP2_ALIGN_VIRAL.out.bam + ch_mapped_bam = MINIMAP2_ALIGN_HOST.out.bam } - WW_SAMTOOLS_INDEX_VIRAL( - ch_viral_bam - ) - viral_bam_index = WW_SAMTOOLS_INDEX_VIRAL.out.bai + WW_SAMTOOLS_INDEX_HOST( + ch_mapped_bam + ) + bam_index = WW_SAMTOOLS_INDEX_HOST.out.bai - WW_SAMTOOLS_FLAGSTAT_VIRAL( - ch_viral_bam.combine(viral_bam_index, by: 0) + WW_SAMTOOLS_FLAGSTAT_HOST( + ch_mapped_bam.combine( + bam_index, + by: 0 ) - ch_ivar=ch_viral_bam.combine(viral_bam_index, by: 0) - WW_IVAR_TRIM(ch_ivar, articDownloadScheme.out.bed) - WW_SAMTOOLS_SORT(WW_IVAR_TRIM.out.bam, viral_genome) - - - FREYJA_UPDATE(params.db_name) - ch_barcodes = FREYJA_UPDATE.out.barcodes - ch_lineages_meta = FREYJA_UPDATE.out.lineages_meta - - BAM_VARIANT_DEMIX_BOOT_FREYJA(WW_SAMTOOLS_SORT.out.bam, file(params.viral_genome), 100, params.db_name, ch_barcodes, ch_lineages_meta) - WW_IVAR_VARIANTS_TO_VCF(BAM_VARIANT_DEMIX_BOOT_FREYJA.out.variants) - vcf = WW_IVAR_VARIANTS_TO_VCF.out.vcf - ch_stats = WW_SEQKIT_STATS.out.stats - - ANNOTATION(vcf, ch_snpeff_db, ch_snpeff_config, params.viral_genome, ch_stats, ch_json) - annotatted_vcf = ANNOTATION.out.gvf - - GVF_PROCESSING_ANNOTATION(annotatted_vcf) + ) + + WW_SAMTOOLS_VIEW( + ch_mapped_bam.combine(bam_index, by: 0), + [[], []], + [] + ) + interleaved = params.interleaved + WW_SAMTOOLS_FASTQ( + WW_SAMTOOLS_VIEW.out.bam, + interleaved + ) + + ch_short_reads = WW_SAMTOOLS_FASTQ.out.fastq + } + + if (params.viral_aligner == 'bwa') { + WW_BWA_INDEX_VIRAL(viral_genome) + viral_genome_index = WW_BWA_INDEX_VIRAL.out.index + reads = ch_short_reads + sorted = params.bwa_sort_bam + WW_BWA_MEM_VIRAL( + reads, + viral_genome_index, + viral_genome, + sorted + ) + ch_viral_bam = WW_BWA_MEM_VIRAL.out.bam + } + else { + + reads = ch_short_reads + bam_format = params.bam_format + //true + cigar_paf_format = params.cigar_paf_format + //false + cigar_bam = params.cigar_bam + //false + MINIMAP2_ALIGN_VIRAL( + reads, + viral_genome, + bam_format, + cigar_paf_format, + cigar_bam + ) + ch_viral_bam = MINIMAP2_ALIGN_VIRAL.out.bam + } + + WW_SAMTOOLS_INDEX_VIRAL( + ch_viral_bam + ) + viral_bam_index = WW_SAMTOOLS_INDEX_VIRAL.out.bai + + WW_SAMTOOLS_FLAGSTAT_VIRAL( + ch_viral_bam.combine(viral_bam_index, by: 0) + ) + ch_ivar = ch_viral_bam.combine(viral_bam_index, by: 0) + WW_IVAR_TRIM(ch_ivar, articDownloadScheme.out.bed) + WW_SAMTOOLS_SORT(WW_IVAR_TRIM.out.bam, viral_genome) + + + FREYJA_UPDATE(params.db_name) + ch_barcodes = FREYJA_UPDATE.out.barcodes + ch_lineages_meta = FREYJA_UPDATE.out.lineages_meta + + BAM_VARIANT_DEMIX_BOOT_FREYJA(WW_SAMTOOLS_SORT.out.bam, file(params.viral_genome), 100, params.db_name, ch_barcodes, ch_lineages_meta) + WW_IVAR_VARIANTS_TO_VCF(BAM_VARIANT_DEMIX_BOOT_FREYJA.out.variants) + vcf = WW_IVAR_VARIANTS_TO_VCF.out.vcf + ch_stats = WW_SEQKIT_STATS.out.stats + + ANNOTATION(vcf, ch_snpeff_db, ch_snpeff_config, params.viral_genome, ch_stats, ch_json) + annotatted_vcf = ANNOTATION.out.gvf + + GVF_PROCESSING_ANNOTATION(annotatted_vcf) emit: - versions = ch_versions // channel: [ path(versions.yml) ] + versions = ch_versions // channel: [ path(versions.yml) ] } - From 8de8f18314b364c86c0af19cb4bbf688471d58b0 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 23:30:10 -0800 Subject: [PATCH 108/161] updated main.nf structure --- main.nf | 54 +++++++++++++++++++++++++++--------------------------- 1 file changed, 27 insertions(+), 27 deletions(-) diff --git a/main.nf b/main.nf index 0cd773cd..8cf61977 100644 --- a/main.nf +++ b/main.nf @@ -9,15 +9,14 @@ script_files = "$baseDir/bin" include { COVIDMVP } from './workflows/covidmvp' include { POXMVP } from './workflows/poxmvp' include { WASTEWATER } from './workflows/virusmvp_wastewater' -//include { FLUMVP } from './workflows/flumvp' // include subworkflows include { CONFIGURE_VIRUSMVP } from './subworkflows/local/virusmvp_config' // include modules -include {printHelp } from './modules/local/help' -include {cidgohHeader } from './modules/local/header' -include {workflowHeader } from './modules/local/wf_header' +include { printHelp } from './modules/local/help' +include { cidgohHeader } from './modules/local/header' +include { workflowHeader } from './modules/local/wf_header' if (params.help){ @@ -61,32 +60,33 @@ workflow { } catch (Exception e) { log.warn "Unable to set permissions for files in $script_files: ${e.message}"} } - CONFIGURE_VIRUSMVP() json_file = file(params.genecoord, checkIfExists: true) - ch_json = [ [ id:params.virus_accession_id ], [ json_file ] ] - - ch_snpeff_db=CONFIGURE_VIRUSMVP.out.ch_snpeff_db - ch_snpeff_config=CONFIGURE_VIRUSMVP.out.ch_snpeff_config - ch_viral_fai=CONFIGURE_VIRUSMVP.out.ch_viral_fai - - if (params.virus_accession_id = "NC_045512.2"){ - println("Executing COVID-MVP") - if (params.wastewater){ - WASTEWATER(ch_json, ch_snpeff_db, ch_snpeff_config, ch_viral_fai) - } - else{ - COVIDMVP(ch_json, ch_snpeff_db, ch_snpeff_config, ch_viral_fai) - } - } + ch_json = Channel.of(tuple([id: params.virus_accession_id], json_file)) + ch_snpeff_db = CONFIGURE_VIRUSMVP.out.ch_snpeff_db + ch_snpeff_config = CONFIGURE_VIRUSMVP.out.ch_snpeff_config - else if (params.virus_accession_id = "NC_063383.1"){ + // Debug: Print channel contents + ch_json.view { "ch_json: $it" } + ch_snpeff_db.view { "ch_snpeff_db: $it" } + ch_snpeff_config.view { "ch_snpeff_config: $it" } + + if (params.wastewater) { + println "Running WASTEWATER workflow" + WASTEWATER(ch_json, ch_snpeff_db, ch_snpeff_config) + } else { + switch(params.virus_accession_id) { + case "NC_045512.2": + println("Executing COVID-MVP") + COVIDMVP(ch_json, ch_snpeff_db, ch_snpeff_config) + break + case "NC_063383.1": println("Executing POX-MVP") - if (params.wastewater){ - WASTEWATER(ch_json, ch_snpeff_db, ch_snpeff_config, ch_viral_fai) - } - else{ - POXMVP(ch_json, ch_snpeff_db, ch_snpeff_config, ch_viral_fai) - } + POXMVP(ch_json, ch_snpeff_db, ch_snpeff_config) + break + default: + error "Unsupported virus accession ID: ${params.virus_accession_id}" + } } + } From 2c0101afffd9c39409c394cfd0f7e8512cf40965 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 23:37:39 -0800 Subject: [PATCH 109/161] updated main.nf structure --- main.nf | 105 ++++++++++++++++++++++++++------------------------------ 1 file changed, 49 insertions(+), 56 deletions(-) diff --git a/main.nf b/main.nf index 8cf61977..f6516c22 100644 --- a/main.nf +++ b/main.nf @@ -3,63 +3,61 @@ // enable dsl2 nextflow.enable.dsl = 2 -script_files = "$baseDir/bin" - // include workflows -include { COVIDMVP } from './workflows/covidmvp' -include { POXMVP } from './workflows/poxmvp' -include { WASTEWATER } from './workflows/virusmvp_wastewater' +include { COVIDMVP } from './workflows/covidmvp' +include { POXMVP } from './workflows/poxmvp' +include { WASTEWATER } from './workflows/virusmvp_wastewater' // include subworkflows include { CONFIGURE_VIRUSMVP } from './subworkflows/local/virusmvp_config' // include modules -include { printHelp } from './modules/local/help' -include { cidgohHeader } from './modules/local/header' -include { workflowHeader } from './modules/local/wf_header' - +include { printHelp } from './modules/local/help' +include { cidgohHeader } from './modules/local/header' +include { workflowHeader } from './modules/local/wf_header' -if (params.help){ - log.info cidgohHeader() - log.info workflowHeader() - printHelp() - exit 0 +// main workflow +workflow { + script_files = "${baseDir}/bin" + if (params.help) { + log.info(cidgohHeader()) + log.info(workflowHeader()) + printHelp() + exit(0) } -if (params.profile){ - println("Profile should have a single dash: -profile") - System.exit(1) + if (params.profile) { + println("Profile should have a single dash: -profile") + System.exit(1) } -if ( !params.prefix ) { - println("Please supply a prefix for your output files with --prefix") - println("Use --help to print help") - System.exit(1) -} else { - if ( params.prefix =~ /\// ){ - println("The --prefix that you supplied contains a \"/\", please replace it with another character") + if (!params.prefix) { + println("Please supply a prefix for your output files with --prefix") + println("Use --help to print help") System.exit(1) + } + else { + if (params.prefix =~ /\//) { + println("The --prefix that you supplied contains a \"/\", please replace it with another character") + System.exit(1) } -} - -// main workflow -workflow { - main: - - log.info cidgohHeader() - log.info workflowHeader() + } + log.info(cidgohHeader()) + log.info(workflowHeader()) if (!params.skip_permissions) { try { - def scriptFiles = file("$script_files/*") + def scriptFiles = file("${script_files}/*") scriptFiles.each { file -> if (file.isFile()) { - file.setPermissions('rwxr-xr-x') // 755 in octal, more standard permissions + file.setPermissions('rwxr-xr-x') } } - } catch (Exception e) { - log.warn "Unable to set permissions for files in $script_files: ${e.message}"} - } + } + catch (Exception e) { + log.warn("Unable to set permissions for files in ${script_files}: ${e.message}") + } + } CONFIGURE_VIRUSMVP() json_file = file(params.genecoord, checkIfExists: true) ch_json = Channel.of(tuple([id: params.virus_accession_id], json_file)) @@ -67,26 +65,21 @@ workflow { ch_snpeff_config = CONFIGURE_VIRUSMVP.out.ch_snpeff_config // Debug: Print channel contents - ch_json.view { "ch_json: $it" } - ch_snpeff_db.view { "ch_snpeff_db: $it" } - ch_snpeff_config.view { "ch_snpeff_config: $it" } - + ch_json.view { "ch_json: ${it}" } + ch_snpeff_db.view { "ch_snpeff_db: ${it}" } + ch_snpeff_config.view { "ch_snpeff_config: ${it}" } if (params.wastewater) { - println "Running WASTEWATER workflow" - WASTEWATER(ch_json, ch_snpeff_db, ch_snpeff_config) - } else { - switch(params.virus_accession_id) { - case "NC_045512.2": - println("Executing COVID-MVP") - COVIDMVP(ch_json, ch_snpeff_db, ch_snpeff_config) - break - case "NC_063383.1": - println("Executing POX-MVP") - POXMVP(ch_json, ch_snpeff_db, ch_snpeff_config) - break - default: - error "Unsupported virus accession ID: ${params.virus_accession_id}" - } + log.info("Running WASTEWATER workflow") + WASTEWATER(ch_json, ch_snpeff_db, ch_snpeff_config) } + else { + def mvp_workflow = params.virus_accession_id == "NC_045512.2" + ? COVIDMVP + : params.virus_accession_id == "NC_063383.1" + ? POXMVP + : { error("Unsupported virus accession ID: ${params.virus_accession_id}") } + log.info("Executing ${mvp_workflow.name}") + mvp_workflow(ch_json, ch_snpeff_db, ch_snpeff_config) + } } From c3b8080d6f12120d6f0650138664faf887c57dc8 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 23:49:04 -0800 Subject: [PATCH 110/161] updated main.nf structure --- main.nf | 21 +++++++++++---------- 1 file changed, 11 insertions(+), 10 deletions(-) diff --git a/main.nf b/main.nf index f6516c22..a5144b87 100644 --- a/main.nf +++ b/main.nf @@ -18,7 +18,7 @@ include { workflowHeader } from './modules/local/wf_header' // main workflow workflow { - script_files = "${baseDir}/bin" + //script_files = "${baseDir}/bin" if (params.help) { log.info(cidgohHeader()) log.info(workflowHeader()) @@ -47,7 +47,7 @@ workflow { if (!params.skip_permissions) { try { - def scriptFiles = file("${script_files}/*") + def scriptFiles = file("${baseDir}/bin/*") scriptFiles.each { file -> if (file.isFile()) { file.setPermissions('rwxr-xr-x') @@ -72,14 +72,15 @@ workflow { log.info("Running WASTEWATER workflow") WASTEWATER(ch_json, ch_snpeff_db, ch_snpeff_config) } + else if (params.virus_accession_id == "NC_045512.2") { + log.info("Executing COVIDMVP workflow") + COVIDMVP(ch_json, ch_snpeff_db, ch_snpeff_config) + } + else if (params.virus_accession_id == "NC_063383.1") { + log.info("Executing POXMVP workflow") + POXMVP(ch_json, ch_snpeff_db, ch_snpeff_config) + } else { - def mvp_workflow = params.virus_accession_id == "NC_045512.2" - ? COVIDMVP - : params.virus_accession_id == "NC_063383.1" - ? POXMVP - : { error("Unsupported virus accession ID: ${params.virus_accession_id}") } - - log.info("Executing ${mvp_workflow.name}") - mvp_workflow(ch_json, ch_snpeff_db, ch_snpeff_config) + error "Unsupported virus accession ID: ${params.virus_accession_id}" } } From 08a977b633d6910fdabdb6c59fe8e56a9dd3c4b0 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 15 Nov 2024 23:52:16 -0800 Subject: [PATCH 111/161] updated main.nf structure --- main.nf | 5 ++--- 1 file changed, 2 insertions(+), 3 deletions(-) diff --git a/main.nf b/main.nf index a5144b87..fad44fcd 100644 --- a/main.nf +++ b/main.nf @@ -18,7 +18,6 @@ include { workflowHeader } from './modules/local/wf_header' // main workflow workflow { - //script_files = "${baseDir}/bin" if (params.help) { log.info(cidgohHeader()) log.info(workflowHeader()) @@ -55,7 +54,7 @@ workflow { } } catch (Exception e) { - log.warn("Unable to set permissions for files in ${script_files}: ${e.message}") + log.warn("Unable to set permissions for script files: ${e.message}") } } CONFIGURE_VIRUSMVP() @@ -81,6 +80,6 @@ workflow { POXMVP(ch_json, ch_snpeff_db, ch_snpeff_config) } else { - error "Unsupported virus accession ID: ${params.virus_accession_id}" + error("Unsupported virus accession ID: ${params.virus_accession_id}") } } From 58fb48c6d8de2403833a0c7f0bfa47dc60aa6d0b Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 26 Nov 2024 02:13:28 -0800 Subject: [PATCH 112/161] fix missing file --- bin/convert_pokay_to_virusmvp.py | 4 ++-- 1 file changed, 2 insertions(+), 2 deletions(-) diff --git a/bin/convert_pokay_to_virusmvp.py b/bin/convert_pokay_to_virusmvp.py index 8da78b43..71b1e87a 100755 --- a/bin/convert_pokay_to_virusmvp.py +++ b/bin/convert_pokay_to_virusmvp.py @@ -369,7 +369,7 @@ def write_tsv(dframe): # merge on "mutation" and "protein symbol" in index ("original mutation description" and "protein symbol" in functional annotation file) mutation_index = mutation_index.rename(columns={"mutation": "original mutation description", 'pos':'nucleotide position', 'hgvs_aa_mutation':'amino acid mutation','hgvs_nt_mutation':'nucleotide mutation', - 'hgvs_alias':'amino acid mutation alias', 'gene_symbol':'gene'}) + 'hgvs_alias':'amino acid mutation alias', 'gene_symbol':'gene symbol'}) #print("columns", mutation_index.columns) # remove index columns that don't have a nucleotide mutation entry initial_length = mutation_index.shape[0] @@ -382,7 +382,7 @@ def write_tsv(dframe): # drop duplicate rows from mutation index mutation_index = mutation_index.drop_duplicates(subset=index_cols_to_use) # merge - merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'gene'], how='left') #, 'mat_pep' + merged_dataFrame = pd.merge(dataFrame, mutation_index, on=['original mutation description', 'gene symbol'], how='left') #, 'mat_pep' #dups.to_csv('madeline_testing/dups.tsv', sep='\t', index=False) # keep only specified columns, discarding 'pokay_id' here From 1005647ff46b8f06cda53e2f815c301ee71a1d62 Mon Sep 17 00:00:00 2001 From: miseminger Date: Tue, 26 Nov 2024 02:34:01 -0800 Subject: [PATCH 113/161] try fixing 'alias' missing key --- bin/functions.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/bin/functions.py b/bin/functions.py index f6f2a210..63a88f3c 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -583,7 +583,7 @@ def add_alias_names(df, GENE_PROTEIN_POSITIONS_DICT): df.loc[:, 'alias'] = 'n/a' # get list of all NSP, 3CL, and PlPro proteins in the file: - alias_mask = (df['gene_symbol'].str.contains("ORF1ab")) & (df['mat_pep']!='n/a') + alias_mask = (df['gene_symbol'].str.contains("orf1ab")) & (df['mat_pep']!='n/a') nsps_list = sorted(list(set(df[alias_mask]['mat_pep'].tolist()))) if len(nsps_list) > 0: From 4dffc952ff6570966b73d3ac509d1ee7d4a4a4b2 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Tue, 26 Nov 2024 10:08:14 -0800 Subject: [PATCH 114/161] updated config --- conf/eagle.config | 2 +- conf/modules.config | 10 +++++++++- conf/resources.config | 4 ++-- 3 files changed, 12 insertions(+), 4 deletions(-) diff --git a/conf/eagle.config b/conf/eagle.config index d321bca6..9163f27d 100644 --- a/conf/eagle.config +++ b/conf/eagle.config @@ -27,5 +27,5 @@ process { } executor { - queueSize = 12 + queueSize = 64 } diff --git a/conf/modules.config b/conf/modules.config index ab66e8ed..8c3902ef 100644 --- a/conf/modules.config +++ b/conf/modules.config @@ -33,7 +33,7 @@ process { } withName: BBMAP { - ext.args = "maxns=${params.maxns} minlength=${params.minlength} addunderscore tossjunk overwrite=true -Xmx4g" + ext.args = "maxns=${params.maxns} minlength=${params.minlength} addunderscore tossjunk overwrite=true -da" } @@ -116,6 +116,14 @@ process { saveAs: { filename -> filename.equals('versions.yml') ? null : filename } ] } + withName: GVF2TSV { + publishDir = [ + path: { "${params.outdir}/${params.prefix}/SURVEILLANCE/TSV" }, + mode: params.publish_dir_mode, + saveAs: { filename -> filename.equals('versions.yml') ? null : filename } + ] + } + // Wastewater diff --git a/conf/resources.config b/conf/resources.config index 12f7087a..db5839cb 100644 --- a/conf/resources.config +++ b/conf/resources.config @@ -21,10 +21,10 @@ process { // Process-specific resource requirements // NOTE - Please try and re-use the labels below as much as possible. - // These labels are used and recognised by default in DSL2 files hosted on nf-core/modules. + // These labels are used and recognized by default in DSL2 files hosted on nf-core/modules. // If possible, it would be nice to keep the same label naming convention when // adding in your local modules too. - // TODO nf-core: Customise requirements for specific processes. + // TODO nf-core: Customize requirements for specific processes. // See https://www.nextflow.io/docs/latest/config.html#config-process-selectors withLabel:process_single { cpus = { check_max( 1 , 'cpus' ) } From bf550447bc81103ae91cfb588d1dbd5ce4ab7d80 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Tue, 26 Nov 2024 10:08:42 -0800 Subject: [PATCH 115/161] updated subworkflows --- bin/convert_pokay_to_virusmvp.py | 2 +- bin/functions.py | 11 ++---- bin/gvf2tsv.py | 3 +- bin/merge_indices.py | 28 ++++++++++++--- bin/merge_indices.py.bak | 58 ++++++++++++++++++++++++++++++++ 5 files changed, 85 insertions(+), 17 deletions(-) create mode 100755 bin/merge_indices.py.bak diff --git a/bin/convert_pokay_to_virusmvp.py b/bin/convert_pokay_to_virusmvp.py index 8da78b43..519633a7 100755 --- a/bin/convert_pokay_to_virusmvp.py +++ b/bin/convert_pokay_to_virusmvp.py @@ -16,7 +16,7 @@ from pathlib import Path import pandas as pd import csv -from functions import map_pos_to_gene_protein, unnest_multi +from functions import unnest_multi def parse_args(): diff --git a/bin/functions.py b/bin/functions.py index f6f2a210..bb2692ac 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -21,8 +21,7 @@ empty_attributes = empty_attributes.replace(" ", "") -gvf_columns = ['#seqid', '#source', '#type', '#start', '#end', - '#score', '#strand', '#phase', '#attributes'] +gvf_columns = ['#seqid', '#source', '#type', '#start', '#end', '#score', '#strand', '#phase', '#attributes'] vcf_columns = ['#CHROM', 'POS', 'ID', 'REF', 'ALT', 'QUAL', 'FILTER', 'INFO', 'FORMAT', 'unknown'] @@ -34,13 +33,7 @@ ['##species']]) # source: https://hgvs-nomenclature.org/stable/background/standards/#amino-acid-descriptions -amino_acid_codes_dict = {'*': 'Ter', 'A': 'Ala', 'B': 'Asx', 'C': 'Cys', - 'D': 'Asp', 'E': 'Glu', 'F': 'Phe', 'G': 'Gly', - 'H': 'His', 'I': 'Ile', 'K': 'Lys', 'L': 'Leu', - 'M': 'Met', 'N': 'Asn', 'P': 'Pro', 'Q': 'Gln', - 'R': 'Arg', 'S': 'Ser', 'T': 'Thr', 'U': 'Sec', - 'V': 'Val', 'W': 'Trp', 'X': 'Xaa', 'Y': 'Tyr', - 'Z': 'Glx'} +amino_acid_codes_dict = {'*': 'Ter', 'A': 'Ala', 'B': 'Asx', 'C': 'Cys', 'D': 'Asp', 'E': 'Glu', 'F': 'Phe', 'G': 'Gly', 'H': 'His', 'I': 'Ile', 'K': 'Lys', 'L': 'Leu', 'M': 'Met', 'N': 'Asn', 'P': 'Pro', 'Q': 'Gln', 'R': 'Arg', 'S': 'Ser', 'T': 'Thr', 'U': 'Sec', 'V': 'Val', 'W': 'Trp', 'X': 'Xaa', 'Y': 'Tyr', 'Z': 'Glx'} def convert_amino_acid_codes(one_letter_mutation_name): three_letter_code_result = "".join([ diff --git a/bin/gvf2tsv.py b/bin/gvf2tsv.py index 430fd26b..62cdd027 100755 --- a/bin/gvf2tsv.py +++ b/bin/gvf2tsv.py @@ -28,8 +28,7 @@ def parse_args(): def gvf2tsv(gvf): # read in gvf - gvf_columns = ['#seqid', '#source', '#type', '#start', '#end', - '#score', '#strand', '#phase', '#attributes'] + gvf_columns = ['#seqid', '#source', '#type', '#start', '#end', '#score', '#strand', '#phase', '#attributes'] df = pd.read_csv(gvf, sep='\t', names=gvf_columns) # remove pragmas and original header diff --git a/bin/merge_indices.py b/bin/merge_indices.py index fb35c199..d8d30c0c 100755 --- a/bin/merge_indices.py +++ b/bin/merge_indices.py @@ -10,6 +10,7 @@ """ import dask dask.config.set({'dataframe.query-planning': True}) +from dask.distributed import Client import dask.dataframe as dd import argparse @@ -25,30 +26,45 @@ def parse_args(): parser.add_argument('--index_savefile', type=str, default=None, help='TSV filename to save updated \ index of all mutations to') + parser.add_argument('--cpus', type=int, default=1, + help='Number of CPUs to use') return parser.parse_args() if __name__ == '__main__': - args = parse_args() original_index = args.original_index gvf_indices_list = args.gvf_indices index_savefile = args.index_savefile + cpus = args.cpus + + # Set up Dask distributed client with specified CPUs + client = Client(n_workers=cpus) + print(f"Dask client initialized with {cpus} workers. Dashboard available at {client.dashboard_link}") # if an original index is provided, merge the new indices with it - if original_index!=None: + if original_index is not None: indices_to_merge = [original_index] + gvf_indices_list - # if an original index is not provided, make an entirely new index else: indices_to_merge = gvf_indices_list # read all indices into dask df - ddf = dd.read_csv(indices_to_merge, sep='\t', dtype={'alias': 'object', 'alias_protein': 'object', 'hgvs_aa_mutation': 'object', 'hgvs_alias': 'object', 'protein_name': 'object'}) + ddf = dd.read_csv( + indices_to_merge, + sep='\t', + dtype={ + 'alias': 'object', + 'alias_protein': 'object', + 'hgvs_aa_mutation': 'object', + 'hgvs_alias': 'object', + 'protein_name': 'object' + } + ) # fillna to make groupby() work ddf = ddf.fillna('n/a') # specify which columns to group by - group_cols = [x for x in ddf.columns if x!='lineages'] + group_cols = [x for x in ddf.columns if x != 'lineages'] # do groupby operation ddf = ddf.groupby(by=group_cols)['lineages'].apply(','.join).reset_index() # sort by 'pos' @@ -56,3 +72,5 @@ def parse_args(): # save ddf as a single TSV ddf.to_csv(index_savefile, single_file=True, sep='\t', index=False) + + print("Index merging completed. File saved at:", index_savefile) \ No newline at end of file diff --git a/bin/merge_indices.py.bak b/bin/merge_indices.py.bak new file mode 100755 index 00000000..fb35c199 --- /dev/null +++ b/bin/merge_indices.py.bak @@ -0,0 +1,58 @@ +#!/usr/bin/env python3 +# -*- coding: utf-8 -*- +""" +Created on Fri Feb 16 12:00:04 2024 + +@author: madeline + +This script merges multiple mutation indices into one. +If an existing mutation index is provided, the new indices are added to it. +""" +import dask +dask.config.set({'dataframe.query-planning': True}) +import dask.dataframe as dd +import argparse + + +def parse_args(): + parser = argparse.ArgumentParser( + description='Merges mutation indices into one.') + parser.add_argument('--original_index', type=str, default=None, + help='Path to an existing TSV index of all mutations, \ + to merge new indices to') + parser.add_argument('--gvf_indices', type=str, default=None, + nargs='*', help='Paths to GVF indices to merge') + parser.add_argument('--index_savefile', type=str, + default=None, help='TSV filename to save updated \ + index of all mutations to') + + return parser.parse_args() + + +if __name__ == '__main__': + + args = parse_args() + original_index = args.original_index + gvf_indices_list = args.gvf_indices + index_savefile = args.index_savefile + + # if an original index is provided, merge the new indices with it + if original_index!=None: + indices_to_merge = [original_index] + gvf_indices_list + # if an original index is not provided, make an entirely new index + else: + indices_to_merge = gvf_indices_list + + # read all indices into dask df + ddf = dd.read_csv(indices_to_merge, sep='\t', dtype={'alias': 'object', 'alias_protein': 'object', 'hgvs_aa_mutation': 'object', 'hgvs_alias': 'object', 'protein_name': 'object'}) + # fillna to make groupby() work + ddf = ddf.fillna('n/a') + # specify which columns to group by + group_cols = [x for x in ddf.columns if x!='lineages'] + # do groupby operation + ddf = ddf.groupby(by=group_cols)['lineages'].apply(','.join).reset_index() + # sort by 'pos' + ddf = ddf.sort_values("pos") + + # save ddf as a single TSV + ddf.to_csv(index_savefile, single_file=True, sep='\t', index=False) From fe51186f0757639b4f10e398065d40283435f408 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Tue, 26 Nov 2024 10:09:15 -0800 Subject: [PATCH 116/161] updated subworkflows --- subworkflows/local/virusmvp_annotation.nf | 136 +++++++++--------- subworkflows/local/virusmvp_config.nf | 9 +- subworkflows/local/virusmvp_postprocessing.nf | 1 + subworkflows/local/virusmvp_preprocessing.nf | 25 ++-- subworkflows/local/virusmvp_qc.nf | 8 +- subworkflows/local/virusmvp_surveillance.nf | 21 +-- 6 files changed, 98 insertions(+), 102 deletions(-) diff --git a/subworkflows/local/virusmvp_annotation.nf b/subworkflows/local/virusmvp_annotation.nf index 94c3203b..c5d941c5 100644 --- a/subworkflows/local/virusmvp_annotation.nf +++ b/subworkflows/local/virusmvp_annotation.nf @@ -5,88 +5,88 @@ nextflow.enable.dsl = 2 // import modules -include { SNPEFF_ANN } from '../../modules/local/snpeff_ann' -include { VCFTOGVF } from '../../modules/local/vcftogvf' -include { TAGPROBLEMATICSITES_NCOV } from '../../modules/local/tagproblematicsites_ncov' -include { ANNOTATEMATPEPTIDES_NCOV } from '../../modules/local/annotatematpeptides_ncov' +include { SNPEFF_ANN } from '../../modules/local/snpeff_ann' +include { VCFTOGVF } from '../../modules/local/vcftogvf' +include { TAGPROBLEMATICSITES_NCOV } from '../../modules/local/tagproblematicsites_ncov' +include { ANNOTATEMATPEPTIDES_NCOV } from '../../modules/local/annotatematpeptides_ncov' workflow ANNOTATION { take: - annotation_vcf - ch_snpeff_db - ch_snpeff_config - viral_genome - ch_stats - ch_json + annotation_vcf + ch_snpeff_db + ch_snpeff_config + viral_genome + ch_stats + ch_json main: - lineage = true - wastewater_data = [] - - if (!params.skip_problematics_sites && params.virus_accession_id == "NC_045512.2"){ - problematics_sites = file(params.probvcf, checkIfExists: true) - vcf = [ [ id:params.virus_accession_id ], [ problematics_sites ] ] - TAGPROBLEMATICSITES_NCOV(annotation_vcf, vcf) - annotation_vcf=TAGPROBLEMATICSITES_NCOV.out.vcf - } - - if (!params.skip_SNPEFF){ - SNPEFF_ANN ( - annotation_vcf, - ch_snpeff_db, - ch_snpeff_config, - viral_genome - ) - annotation_vcf = SNPEFF_ANN.out.vcf - } - + lineage = true + wastewater_data = [] - if (!params.skip_peptide_annottaion && params.virus_accession_id == "NC_045512.2"){ - ANNOTATEMATPEPTIDES_NCOV( - annotation_vcf, - ch_json - ) - annotation_vcf=ANNOTATEMATPEPTIDES_NCOV.out.vcf - } - - //VCF to GVF transformation - - /*if (ch_json == []){ + if (!params.skip_problematics_sites && params.virus_accession_id == "NC_045512.2") { + problematics_sites = file(params.probvcf, checkIfExists: true) + vcf = [[id: params.virus_accession_id], [problematics_sites]] + TAGPROBLEMATICSITES_NCOV(annotation_vcf, vcf) + annotation_vcf = TAGPROBLEMATICSITES_NCOV.out.vcf + } + + if (!params.skip_SNPEFF) { + SNPEFF_ANN( + annotation_vcf, + ch_snpeff_db, + ch_snpeff_config, + viral_genome + ) + annotation_vcf = SNPEFF_ANN.out.vcf + } + + + if (!params.skip_peptide_annottaion && params.virus_accession_id == "NC_045512.2") { + ch_json_value = ch_json.first() + ANNOTATEMATPEPTIDES_NCOV( + annotation_vcf, + ch_json_value + ) + annotation_vcf = ANNOTATEMATPEPTIDES_NCOV.out.vcf + } + + //VCF to GVF transformation + + /*if (ch_json == []){ json_file = file(params.genecoord, checkIfExists: true) json = [ [ id:params.virus_accession_id ], [ json_file ] ] } else{ json = ch_json }*/ - threshold=0.75 - if (params.wastewater){ - lineage = [] - wastewater_data = true - data_description = "Wastewater" - } - else{ - data_description = "Clinical" - } - if (ch_stats){ - ch_stats = ch_stats.map{it[1]} - } + threshold = 0.75 + if (params.wastewater) { + lineage = [] + wastewater_data = true + data_description = "Wastewater" + } + else { + data_description = "Clinical" + } + if (ch_stats) { + ch_stats = ch_stats.map { it[1] } + } - if (params.mode == 'user'){ - lineage = [] - } + if (params.mode == 'user') { + lineage = [] + } - VCFTOGVF( - annotation_vcf, - ch_stats, - threshold, - ch_json, - lineage, - wastewater_data, - data_description, - ) - gvf = VCFTOGVF.out.gvf + VCFTOGVF( + annotation_vcf, + ch_stats, + threshold, + ch_json_value, + lineage, + wastewater_data, + data_description + ) + gvf = VCFTOGVF.out.gvf - emit: - gvf + gvf } diff --git a/subworkflows/local/virusmvp_config.nf b/subworkflows/local/virusmvp_config.nf index ad3d0668..9de8aec5 100644 --- a/subworkflows/local/virusmvp_config.nf +++ b/subworkflows/local/virusmvp_config.nf @@ -8,10 +8,11 @@ include { SNPEFF_BUILD } from '../../modules/local/snpeff_build' include { SAMTOOLS_FAIDX } from '../../modules/nf-core/samtools/faidx/main' workflow CONFIGURE_VIRUSMVP { + main: ch_snpeff_db = Channel.empty() ch_snpeff_config = Channel.empty() - ch_viral_fai = Channel.empty() + //ch_viral_fai = Channel.empty() SNPEFF_BUILD( params.viral_genome, @@ -21,11 +22,11 @@ workflow CONFIGURE_VIRUSMVP { ch_snpeff_db = SNPEFF_BUILD.out.db ch_snpeff_config = SNPEFF_BUILD.out.config - SAMTOOLS_FAIDX([[id: params.virus_accession_id], params.viral_genome], [[], []]) - ch_viral_fai = SAMTOOLS_FAIDX.out.fai + //SAMTOOLS_FAIDX([[id: params.virus_accession_id], params.viral_genome], [[], []]) + //ch_viral_fai = SAMTOOLS_FAIDX.out.fai emit: ch_snpeff_db ch_snpeff_config - ch_viral_fai + //ch_viral_fai } diff --git a/subworkflows/local/virusmvp_postprocessing.nf b/subworkflows/local/virusmvp_postprocessing.nf index 1ddb4a18..5e7fa4a1 100644 --- a/subworkflows/local/virusmvp_postprocessing.nf +++ b/subworkflows/local/virusmvp_postprocessing.nf @@ -37,4 +37,5 @@ workflow POSTPROCESSING { MERGE_LOGFILES(logheader, ch_logs, ch_indexfile) + } diff --git a/subworkflows/local/virusmvp_preprocessing.nf b/subworkflows/local/virusmvp_preprocessing.nf index 18791a96..02faead1 100644 --- a/subworkflows/local/virusmvp_preprocessing.nf +++ b/subworkflows/local/virusmvp_preprocessing.nf @@ -1,5 +1,4 @@ #!/usr/bin/env nextflow - nextflow.enable.dsl = 2 // import modules @@ -7,7 +6,6 @@ include { EXTRACTVARIANTS } from '../../modules/local/extractVariants' include { EXTRACTMETADATA } from '../../modules/local/extractMetadata' include { SEQKIT_GREP } from '../../modules/nf-core/seqkit/grep/main' - workflow PREPROCESSING { take: metadata @@ -41,26 +39,29 @@ workflow PREPROCESSING { criteria = Channel.of(params.grouping_criteria) EXTRACTVARIANTS(variants, metadata, variantfile, virusseq, criteria, variable, true) - EXTRACTVARIANTS.out.txt .splitText() - .map { id, voc -> tuple([[id: voc.tokenize(':')[1].replaceAll(" ", "_").trim()], voc.replaceAll(" ", "_").trim()]) } + .map { item -> + def (meta, data) = item + def (key, value) = data.split(':', 2) + [[id: value.trim()], data.trim()] + } .set { ch_group } if (EXTRACTVARIANTS.out.log) { logfile = EXTRACTVARIANTS.out.log } + EXTRACTMETADATA(metadata, ch_group, true) + ids_channel = EXTRACTMETADATA.out.txt + .map { it -> it[1] } + .flatten() + .map { file -> + def fileName = file.name.take(file.name.lastIndexOf('.')) + [[id: fileName], file] + } - if (params.grouping_criteria == "time") { - ids_channel = EXTRACTMETADATA.out.txt.map { it -> it[1] }.flatten() - ids_channel.view() - } - else { - ids = EXTRACTMETADATA.out.txt - ids_channel = ids.map { it[1] } - } SEQKIT_GREP(sequences, ids_channel) emit: diff --git a/subworkflows/local/virusmvp_qc.nf b/subworkflows/local/virusmvp_qc.nf index 6e1b4227..add49606 100644 --- a/subworkflows/local/virusmvp_qc.nf +++ b/subworkflows/local/virusmvp_qc.nf @@ -8,14 +8,14 @@ include { SEQKIT_STATS } from '../../modules/nf-core/seqkit/stats/main' workflow QUALITYCONTROL { take: - sequences_grouped + sequences ch_collected_sequences main: - BBMAP(sequences_grouped) + BBMAP(sequences) SEQKIT_STATS(ch_collected_sequences) emit: - sequences_grouped = BBMAP.out.fasta - stats = SEQKIT_STATS.out.stats + sequences = BBMAP.out.fasta + stats = SEQKIT_STATS.out.stats } diff --git a/subworkflows/local/virusmvp_surveillance.nf b/subworkflows/local/virusmvp_surveillance.nf index c2abb9c6..15ed2869 100644 --- a/subworkflows/local/virusmvp_surveillance.nf +++ b/subworkflows/local/virusmvp_surveillance.nf @@ -4,22 +4,15 @@ nextflow.enable.dsl = 2 // import modules -include { surveillanceRawTsv } from '../../modules/local/archive/custom' -include { surveillancePDF } from '../../modules/local/archive/custom' +include { GVF2TSV } from '../../modules/local/gvf2tsv' +//include { surveillancePDF } from '../../modules/local/archive/custom' -workflow surveillance { +workflow SURVEILLANCE { take: - ch_gvf - ch_variant - ch_stats - ch_surveillanceIndicators - ch_metadata + ch_gvf main: - surveillanceRawTsv(ch_gvf, ch_variant.combine(ch_stats)) - surveillancePDF(surveillanceRawTsv.out.surveillancetsv.flatten(), ch_surveillanceIndicators, ch_metadata) - ch_surv = surveillancePDF.out.surveillance_pdf - - emit: - ch_surv + GVF2TSV(ch_gvf) + //surveillancePDF(surveillanceRawTsv.out.surveillancetsv.flatten(), ch_surveillanceIndicators, ch_metadata) + //ch_surv = surveillancePDF.out.surveillance_pdf } From 90995b7a8e42582aed9630c2cb4cd3b64deea79f Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Tue, 26 Nov 2024 10:09:43 -0800 Subject: [PATCH 117/161] updated modules --- modules/local/bbmap_reformat.nf | 19 +++++------ modules/local/extractMetadata.nf | 2 +- modules/local/extractVariants.nf | 6 ++-- modules/local/gvf2tsv.nf | 46 ++++++++++++++++++++++++++ modules/local/mergeIndices.nf | 3 ++ modules/nf-core/minimap2/align/main.nf | 30 ++++++++--------- modules/nf-core/seqkit/grep/main.nf | 24 ++++++-------- 7 files changed, 87 insertions(+), 43 deletions(-) create mode 100644 modules/local/gvf2tsv.nf diff --git a/modules/local/bbmap_reformat.nf b/modules/local/bbmap_reformat.nf index afadf604..37b65ac7 100644 --- a/modules/local/bbmap_reformat.nf +++ b/modules/local/bbmap_reformat.nf @@ -1,21 +1,19 @@ process BBMAP { - tag "$meta.id" - + tag "${meta.id}" conda "bioconda::bbmap=39.01" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/bbmap:39.01--h92535d8_1': - 'microbiomedata/bbtools:39.01'}" - + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/bbmap:39.01--h92535d8_1' + : 'microbiomedata/bbtools:39.01'}" label 'dev_env' input: - tuple val(meta), path(sequence) + tuple val(meta), path(sequence) output: - tuple val(meta), path("*.fasta"), emit: fasta + tuple val(meta), path("*.fasta"), emit: fasta when: - sequence.size() > 0 + sequence.size() > 0 script: def args = task.ext.args ?: '' @@ -23,7 +21,8 @@ process BBMAP { reformat.sh \\ in=${sequence} \\ out=${sequence.baseName}.qc.fasta \\ - $args + threads=2 \\ + ${args} """ } diff --git a/modules/local/extractMetadata.nf b/modules/local/extractMetadata.nf index 69568909..f892978a 100644 --- a/modules/local/extractMetadata.nf +++ b/modules/local/extractMetadata.nf @@ -1,5 +1,5 @@ process EXTRACTMETADATA { - tag "${meta.id}" + tag "${meta2.id}" conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' diff --git a/modules/local/extractVariants.nf b/modules/local/extractVariants.nf index b4baaeab..98fa35cf 100644 --- a/modules/local/extractVariants.nf +++ b/modules/local/extractVariants.nf @@ -15,12 +15,12 @@ process EXTRACTVARIANTS { val time output: - tuple val(meta2), path("*.txt"), emit: txt - tuple val(meta2), path("*.log"), emit: log, optional: true + tuple val(meta), path("*.txt"), emit: txt + tuple val(meta), path("*.log"), emit: log, optional: true script: - def prefix = task.ext.prefix ?: "${meta2.id}" + def prefix = task.ext.prefix ?: "${meta.id}" def val_variant_file = variant_file ? "--variants ${variants}" : '' def virusseq_update = virusseq ? "--virusseq" : '' def val_time = time ? "--start_date ${params.start_date} --end_date ${params.end_date}" : '' diff --git a/modules/local/gvf2tsv.nf b/modules/local/gvf2tsv.nf new file mode 100644 index 00000000..4b6e26ab --- /dev/null +++ b/modules/local/gvf2tsv.nf @@ -0,0 +1,46 @@ +process GVF2TSV { + tag { "${meta.id}" } + label 'process_low' + + conda "conda-forge::pandas=1.4.3" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' + : 'amancevice/pandas:1.4.3'}" + + input: + tuple val(meta), path(gvf) + + output: + tuple val(meta), path("*.tsv"), emit: surveillancetsv + path "versions.yml", emit: versions + + when: + task.ext.when == null || task.ext.when + + script: + def args = task.ext.args ?: '' + def prefix = task.ext.prefix ?: "${meta.id}" + //def mode_command = meta.mode == 'user' ? "--user" : "--all_variants" + """ + gvf2tsv.py \\ + --gvf_file ${gvf} \\ + ${args} \\ + --outtsv ${prefix}.tsv + + cat <<-END_VERSIONS > versions.yml + "${task.process}": + gvf2tsv: \$(gvf2tsv.py --version 2>&1 | sed 's/^.*gvf2tsv.py //; s/ .*\$//') + END_VERSIONS + """ + + stub: + def prefix = task.ext.prefix ?: "${meta.id}" + """ + touch ${prefix}.tsv + + cat <<-END_VERSIONS > versions.yml + "${task.process}": + gvf2tsv: \$(gvf2tsv.py --version 2>&1 | sed 's/^.*gvf2tsv.py //; s/ .*\$//') + END_VERSIONS + """ +} diff --git a/modules/local/mergeIndices.nf b/modules/local/mergeIndices.nf index 0b46e0eb..c2cddac0 100644 --- a/modules/local/mergeIndices.nf +++ b/modules/local/mergeIndices.nf @@ -1,5 +1,7 @@ process MERGE_INDICES { tag "${meta.id}" + cpus 6 + conda "conda-forge::dask=2023.10.1" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'biocontainers/dask:2023.10.1-py11-ol9_cv1' @@ -20,6 +22,7 @@ process MERGE_INDICES { merge_indices.py \\ --gvf_indices ${index} \\ ${last_index} \\ + --cpus ${task.cpus} \\ --index_savefile ${end_date}.index.tsv """ } diff --git a/modules/nf-core/minimap2/align/main.nf b/modules/nf-core/minimap2/align/main.nf index 100a8b31..9a7881d7 100644 --- a/modules/nf-core/minimap2/align/main.nf +++ b/modules/nf-core/minimap2/align/main.nf @@ -1,12 +1,10 @@ process MINIMAP2_ALIGN { - tag "$meta.id" + tag "${meta.id}" label 'process_medium' - - // Note: the versions here need to match the versions used in the mulled container below and minimap2/index conda "${moduleDir}/environment.yml" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/mulled-v2-66534bcbb7031a148b13e2ad42583020b9cd25c4:365b17b986c1a60c1b82c6066a9345f38317b763-0' : - 'quay.io/biocontainers/mulled-v2-66534bcbb7031a148b13e2ad42583020b9cd25c4:365b17b986c1a60c1b82c6066a9345f38317b763-0' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/mulled-v2-66534bcbb7031a148b13e2ad42583020b9cd25c4:365b17b986c1a60c1b82c6066a9345f38317b763-0' + : 'quay.io/biocontainers/mulled-v2-66534bcbb7031a148b13e2ad42583020b9cd25c4:365b17b986c1a60c1b82c6066a9345f38317b763-0'}" input: tuple val(meta), path(reads) @@ -18,13 +16,13 @@ process MINIMAP2_ALIGN { output: tuple val(meta), path("*.paf"), optional: true, emit: paf tuple val(meta), path("*.bam"), optional: true, emit: bam - path "versions.yml" , emit: versions + path "versions.yml", emit: versions when: task.ext.when == null || task.ext.when script: - def args = task.ext.args ?: '' + def args = task.ext.args ?: '' def args2 = task.ext.args2 ?: '' def prefix = task.ext.prefix ?: "${meta.id}" def bam_output = bam_format ? "-a | samtools sort -@ ${task.cpus} -o ${prefix}.bam ${args2}" : "-o ${prefix}.paf" @@ -32,13 +30,13 @@ process MINIMAP2_ALIGN { def set_cigar_bam = cigar_bam && bam_format ? "-L" : '' """ minimap2 \\ - $args \\ - -t $task.cpus \\ + ${args} \\ + -t ${task.cpus} \\ ${reference ?: reads} \\ - $reads \\ - $cigar_paf \\ - $set_cigar_bam \\ - $bam_output + ${reads} \\ + ${cigar_paf} \\ + ${set_cigar_bam} \\ + ${bam_output} cat <<-END_VERSIONS > versions.yml @@ -51,11 +49,11 @@ process MINIMAP2_ALIGN { def prefix = task.ext.prefix ?: "${meta.id}" def output_file = bam_format ? "${prefix}.bam" : "${prefix}.paf" """ - touch $output_file + touch ${output_file} cat <<-END_VERSIONS > versions.yml "${task.process}": minimap2: \$(minimap2 --version 2>&1) END_VERSIONS """ -} \ No newline at end of file +} diff --git a/modules/nf-core/seqkit/grep/main.nf b/modules/nf-core/seqkit/grep/main.nf index 3638be99..7ef35bc2 100644 --- a/modules/nf-core/seqkit/grep/main.nf +++ b/modules/nf-core/seqkit/grep/main.nf @@ -1,27 +1,25 @@ process SEQKIT_GREP { - tag "$meta.id" + tag "${meta2.id}" label 'process_low' - - conda "${moduleDir}/environment.yml" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/seqkit:2.4.0--h9ee0642_0': - 'quay.io/biocontainers/seqkit:2.4.0--h9ee0642_0' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/seqkit:2.4.0--h9ee0642_0' + : 'quay.io/biocontainers/seqkit:2.4.0--h9ee0642_0'}" input: tuple val(meta), path(sequence) - path pattern + tuple val(meta2), path(pattern) output: - tuple val(meta), path("*.{fa,fq}.gz") , emit: filter - path "versions.yml" , emit: versions + tuple val(meta2), path("*.{fa,fq}.gz"), emit: filter + path "versions.yml", emit: versions when: task.ext.when == null || task.ext.when script: def args = task.ext.args ?: '' - def prefix = task.ext.prefix ?: "${meta.id}" + def prefix = task.ext.prefix ?: "${meta2.id}" // fasta or fastq. Exact pattern match .fasta or .fa suffix with optional .gz (gzip) suffix def suffix = task.ext.suffix ?: "${sequence}" ==~ /(.*f[astn]*a(.gz)?$)/ ? "fa" : "fq" def pattern_file = pattern ? "-f ${pattern}" : "" @@ -29,8 +27,8 @@ process SEQKIT_GREP { """ seqkit \\ grep \\ - $args \\ - --threads $task.cpus \\ + ${args} \\ + --threads ${task.cpus} \\ ${pattern_file} \\ ${sequence} \\ -o ${prefix}.${suffix}.gz \\ @@ -43,7 +41,7 @@ process SEQKIT_GREP { stub: def args = task.ext.args ?: '' - def prefix = task.ext.prefix ?: "${meta.id}" + def prefix = task.ext.prefix ?: "${meta2.id}" // fasta or fastq. Exact pattern match .fasta or .fa suffix with optional .gz (gzip) suffix def suffix = task.ext.suffix ?: "${sequence}" ==~ /(.*f[astn]*a(.gz)?$)/ ? "fa" : "fq" From 38468361a451a878fef489546763b87efb567e18 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Tue, 26 Nov 2024 10:10:11 -0800 Subject: [PATCH 118/161] updated main file --- main.nf | 4 ---- 1 file changed, 4 deletions(-) diff --git a/main.nf b/main.nf index fad44fcd..9666e918 100644 --- a/main.nf +++ b/main.nf @@ -63,10 +63,6 @@ workflow { ch_snpeff_db = CONFIGURE_VIRUSMVP.out.ch_snpeff_db ch_snpeff_config = CONFIGURE_VIRUSMVP.out.ch_snpeff_config - // Debug: Print channel contents - ch_json.view { "ch_json: ${it}" } - ch_snpeff_db.view { "ch_snpeff_db: ${it}" } - ch_snpeff_config.view { "ch_snpeff_config: ${it}" } if (params.wastewater) { log.info("Running WASTEWATER workflow") WASTEWATER(ch_json, ch_snpeff_db, ch_snpeff_config) From 7fe746c1203bc89c8bff808a76b5686027bd657e Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Tue, 26 Nov 2024 10:10:38 -0800 Subject: [PATCH 119/161] updated workflows file --- workflows/covidmvp.nf | 32 +++++++++++++++----------------- workflows/poxmvp.nf | 6 +++--- 2 files changed, 18 insertions(+), 20 deletions(-) diff --git a/workflows/covidmvp.nf b/workflows/covidmvp.nf index 83276dd9..4b313014 100644 --- a/workflows/covidmvp.nf +++ b/workflows/covidmvp.nf @@ -5,7 +5,7 @@ nextflow.enable.dsl = 2 include { PREPROCESSING } from '../subworkflows/local/virusmvp_preprocessing' include { VARIANT_CALLING } from '../subworkflows/local/virusmvp_variantcalling' include { ANNOTATION } from '../subworkflows/local/virusmvp_annotation' -include { surveillance } from '../subworkflows/local/virusmvp_surveillance' +include { SURVEILLANCE } from '../subworkflows/local/virusmvp_surveillance' include { GVF_PROCESSING_ANNOTATION } from '../subworkflows/local/virusmvp_gvf_processing_annotations' include { QUALITYCONTROL } from '../subworkflows/local/virusmvp_qc' include { VIRALAI } from '../subworkflows/local/viralai/viralai_datadownload' @@ -18,8 +18,8 @@ include { METADATA_HARMONIZER } from '../modules/local/harmonize_metadata' workflow COVIDMVP { take: - ch_json - ch_snpeff_db + ch_json + ch_snpeff_db ch_snpeff_config main: @@ -54,28 +54,23 @@ workflow COVIDMVP { } if (!params.skip_classification) { CLASSIFICATION(metadata, sequences) - metadata = CLASSIFICATION.out.metadata + metadata = CLASSIFICATION.out.merged_metadata } PREPROCESSING(metadata, sequences) metadata = PREPROCESSING.out.metadata sequences = PREPROCESSING.out.sequences - sequences - .map { fasta_files -> - tuple([[id: fasta_files.getBaseName(2)], [fasta_files]]) - } - .set { sequences_grouped } + // Step 2: Process SEQKIT_GREP output - sequences - .map { [it[1]] } + ch_collected_sequences = sequences + .map { it[1] } .collect() - .map { sequences -> [[id: "seqkit_stat"], sequences] } - .set { ch_collected_sequences } + .map { seqs -> [[id: "seqkit_stat"], seqs] } if (!params.skip_qc) { - QUALITYCONTROL(sequences_grouped, ch_collected_sequences) - sequences_grouped = QUALITYCONTROL.out.sequences_grouped + QUALITYCONTROL(sequences, ch_collected_sequences) + sequences_grouped = QUALITYCONTROL.out.sequences ch_stats = QUALITYCONTROL.out.stats } } @@ -87,12 +82,13 @@ workflow COVIDMVP { } else { if (!params.skip_qc) { - QUALITYCONTROL(sequences, sequences) - sequences_grouped = QUALITYCONTROL.out.sequences_grouped + QUALITYCONTROL(sequences, ch_collected_sequences) + sequences_grouped = QUALITYCONTROL.out.sequences ch_stats = QUALITYCONTROL.out.stats } } } + if (!skip_variant_calling == true) { VARIANT_CALLING(sequences_grouped, params.viral_genome, params.viral_genome_fai) annotation_vcf = VARIANT_CALLING.out.vcf @@ -106,4 +102,6 @@ workflow COVIDMVP { if (!params.skip_postprocessing) { POSTPROCESSING(annotated_gvf, PREPROCESSING.out.logfile) } + + SURVEILLANCE(annotated_gvf) } diff --git a/workflows/poxmvp.nf b/workflows/poxmvp.nf index a7d16e0a..1f8c3026 100644 --- a/workflows/poxmvp.nf +++ b/workflows/poxmvp.nf @@ -5,7 +5,7 @@ nextflow.enable.dsl = 2 include { PREPROCESSING } from '../subworkflows/local/virusmvp_preprocessing' include { VARIANT_CALLING } from '../subworkflows/local/virusmvp_variantcalling' include { ANNOTATION } from '../subworkflows/local/virusmvp_annotation' -include { surveillance } from '../subworkflows/local/virusmvp_surveillance' +include { SURVEILLANCE } from '../subworkflows/local/virusmvp_surveillance' include { GVF_PROCESSING_ANNOTATION } from '../subworkflows/local/virusmvp_gvf_processing_annotations' include { QUALITYCONTROL } from '../subworkflows/local/virusmvp_qc' //include {VIRALAI } from '../subworkflows/local/viralai/viralai_datadownload' @@ -18,8 +18,8 @@ include { METADATA_HARMONIZER } from '../modules/local/harmonize_metadata' workflow POXMVP { take: - ch_json - ch_snpeff_db + ch_json + ch_snpeff_db ch_snpeff_config main: From c7195b942c43cd3cca837cd3938e515e513de44e Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Tue, 26 Nov 2024 10:11:35 -0800 Subject: [PATCH 120/161] updated nextflow config --- nextflow.config | 35 +++++++++++++++++++++++++++++++++++ 1 file changed, 35 insertions(+) diff --git a/nextflow.config b/nextflow.config index 979927bb..f92b67b8 100644 --- a/nextflow.config +++ b/nextflow.config @@ -17,6 +17,41 @@ includeConfig 'conf/nf-ncov-voc.config' includeConfig 'conf/profiles.config' includeConfig 'conf/modules.config' +process { + withName: 'PROCESS_VIRALAI_METADATA' { + memory = '16 GB' // Increase this value as needed + } + withName: 'METADATA_HARMONIZER' { + memory = '16 GB' // Increase this value as needed + } + withName: 'EXTRACTVARIANTS' { + memory = '16 GB' // Increase this value as needed + } + withName: 'EXTRACTMETADATA' { + memory = '16 GB' // Increase this value as needed + } + withName: 'MINIMAP2_ALIGN' { + memory = '16 GB' // Increase this value as needed + } + withName: 'SAMTOOLS_SORT' { + memory = '16 GB' // Increase this value as needed + } + withName: 'SAMTOOLS_STATS' { + memory = '16 GB' // Increase this value as needed + } + withName: 'FREEBAYES' { + memory = '64 GB' // Increase this value as needed + } + withName: 'MERGE_LOGFILES' { + memory = '32 GB' // Increase this value as needed + } + withName: 'MERGE_INDICES' { + memory = '32 GB' // Increase this value as needed + } + + + +} // Export these variables to prevent local Python/R libraries from conflicting with those in the container env { From b80444df6028475b623d01cf5db0905f1876576a Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Tue, 26 Nov 2024 10:12:25 -0800 Subject: [PATCH 121/161] vscode nextflow extension --- .vscode/settings.json | 7 +++---- 1 file changed, 3 insertions(+), 4 deletions(-) diff --git a/.vscode/settings.json b/.vscode/settings.json index 666a01db..f8b7b4ea 100644 --- a/.vscode/settings.json +++ b/.vscode/settings.json @@ -1,7 +1,6 @@ { - "cSpell.words": [ - "bioinformatics" - ], + "cSpell.words": ["bioinformatics", "cpus"], "nextflow.debug": true, - "nextflow.formatting.harshilAlignment": true + "nextflow.formatting.harshilAlignment": true, + "nextflow.java.home": "/cvmfs/soft.computecanada.ca/easybuild/software/2020/Core/java/17.0.2/" } From 847d30bea9df1b6a1545f23d14edf49025498a6a Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 28 Nov 2024 03:19:29 -0800 Subject: [PATCH 122/161] fix 'Pl_pro' alias error --- bin/functions.py | 2 ++ 1 file changed, 2 insertions(+) diff --git a/bin/functions.py b/bin/functions.py index d64121c2..0cd6ab4d 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -603,6 +603,8 @@ def add_alias_names(df, GENE_PROTEIN_POSITIONS_DICT): # for each nsp in nsps_list, operate on the number column based on the nsp start coordinates for nsp in nsps_list: + if nsp=='PL_proPLpro': + nsp='PL_pro' nsp_start_aa = int(GENE_PROTEIN_POSITIONS_DICT[nsp]["aa_start"]) nsp_protein_id = GENE_PROTEIN_POSITIONS_DICT[nsp]["protein_id"] nsp_mask = df['mat_pep']==nsp From c2b571dbd5b11ef47982e5ef720c1c4ec0f0975d Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 28 Nov 2024 18:26:07 -0800 Subject: [PATCH 123/161] Make all index column names lowercase --- bin/gvf2indexandlog.py | 4 ++-- 1 file changed, 2 insertions(+), 2 deletions(-) diff --git a/bin/gvf2indexandlog.py b/bin/gvf2indexandlog.py index 24f6313f..8efdb2be 100755 --- a/bin/gvf2indexandlog.py +++ b/bin/gvf2indexandlog.py @@ -49,7 +49,7 @@ def parse_args(): # create index from GVF # make empty index df - index_cols=['pos', 'mutation', 'hgvs_aa_mutation', 'hgvs_nt_mutation', 'gene_name', 'gene_symbol', 'protein_name', 'protein_symbol', 'alias', 'hgvs_alias', 'mat_pep', 'Pokay_annotation', 'lineages'] + index_cols=['pos', 'mutation', 'hgvs_aa_mutation', 'hgvs_nt_mutation', 'gene_name', 'gene_symbol', 'protein_name', 'protein_symbol', 'alias', 'hgvs_alias', 'mat_pep', 'pokay_annotation', 'lineages'] index = pd.DataFrame(np.empty((gvf.shape[0], len(index_cols))), columns=index_cols) # populate index df with gvf info index['pos'] = gvf['#start'] @@ -63,7 +63,7 @@ def parse_args(): index['gene_symbol'] = gvf['gene_symbol'] index['protein_name'] = gvf['protein_name'] index['protein_symbol'] = gvf['protein_symbol'] - index['Pokay_annotation'] = gvf["variant_functional_effect_description"].notna() + index['pokay_annotation'] = gvf["variant_functional_effect_description"].notna() index['lineages'] = gvf['viral_lineage'] # tidying index = index.drop_duplicates() From ad48161c3dddeac68a35cf0a4d01d87f6c7a9fdd Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 28 Nov 2024 18:27:39 -0800 Subject: [PATCH 124/161] comment out index row removal before merge --- bin/convert_pokay_to_virusmvp.py | 2 ++ 1 file changed, 2 insertions(+) diff --git a/bin/convert_pokay_to_virusmvp.py b/bin/convert_pokay_to_virusmvp.py index 5912b945..ce8cb52e 100755 --- a/bin/convert_pokay_to_virusmvp.py +++ b/bin/convert_pokay_to_virusmvp.py @@ -371,11 +371,13 @@ def write_tsv(dframe): 'hgvs_aa_mutation':'amino acid mutation','hgvs_nt_mutation':'nucleotide mutation', 'hgvs_alias':'amino acid mutation alias', 'gene_symbol':'gene symbol'}) #print("columns", mutation_index.columns) + ''' # remove index columns that don't have a nucleotide mutation entry initial_length = mutation_index.shape[0] mutation_index = mutation_index[mutation_index['nucleotide mutation'].notna()] after_length = mutation_index.shape[0] print("Removed " + str(initial_length - after_length) + "/" + str(after_length) + " mutation index rows that are missing a nucleotide mutation") + ''' # remove doubled columns from dataFrame index_cols_to_use = ['nucleotide position', 'nucleotide mutation', 'amino acid mutation', 'amino acid mutation alias'] dataFrame = dataFrame.drop(columns=index_cols_to_use) From 4db8d7315ce2ae1c55cfb36113d6fe23983854c8 Mon Sep 17 00:00:00 2001 From: miseminger Date: Thu, 28 Nov 2024 20:06:02 -0800 Subject: [PATCH 125/161] capture mat_pep_acc from VCF --- bin/functions.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/bin/functions.py b/bin/functions.py index 0cd6ab4d..3b0385b7 100755 --- a/bin/functions.py +++ b/bin/functions.py @@ -361,7 +361,7 @@ def parse_INFO(df, var_cols): # return INFO dataframe with named columns, includ cols_to_extract = ['DP', 'ps_filter', 'ps_exc', 'EFF', 'mat_pep', 'mat_pep_desc', 'mat_pep_acc'] info = pd.DataFrame(columns=cols_to_extract) for col in cols_to_extract: - pat = str(col) + "\=(.*?)\;" + pat = str(col) + "\=(.*?)(?=[\;]|$)" info[col] = df['INFO'].str.extract(pat) # rename uppercase columns as lowercase info = info.rename(columns={'DP':'dp', 'EFF':'eff'}) From beac4f378f8a70c5605b49e48b54b9cf70eaddf3 Mon Sep 17 00:00:00 2001 From: miseminger Date: Fri, 29 Nov 2024 00:24:50 -0800 Subject: [PATCH 126/161] fix all relevant unequal length columns by adding nans --- ...splitmutationnames_functionalannotation.py | 37 +++++++++---------- 1 file changed, 17 insertions(+), 20 deletions(-) diff --git a/bin/splitmutationnames_functionalannotation.py b/bin/splitmutationnames_functionalannotation.py index 42265e0e..3a96dfa0 100755 --- a/bin/splitmutationnames_functionalannotation.py +++ b/bin/splitmutationnames_functionalannotation.py @@ -72,26 +72,23 @@ def parse_args(): df.loc[df[column].notna(), len_count] = df[column].str.len() # make sure all columns have the same number of elements; if they don't, throw an error - if not (df['original mutation description length'].equals(df['nucleotide position length'])): - print("Original mutation description and nucleotide position columns are of unequal length") - if not (df['nucleotide mutation length'].equals(df['nucleotide position length'])): - print("Nucleotide mutation and nucleotide position columns are of unequal length") - if not (df['amino acid mutation length'].equals(df['nucleotide position length'])): - print("Amino acid mutation and nucleotide position columns are of unequal length") - if not (df['amino acid mutation alias length'].equals(df['nucleotide position length'])): - print("Amino acid mutation alias and nucleotide position columns are of unequal length") - # this is only column that SHOULD have an issue, so the solution is hardcoded here: - # calculate how many elements to add to each list - df['to_add'] = df['nucleotide position length'] - df['amino acid mutation alias length'] - # convert columns to lists of lists - A_list = df['amino acid mutation alias'].tolist() # column that needs padding with NaNs, represented as a nested list - add_list = df['to_add'].tolist() # list of integers representing how many elements to add to each list - na_list = [np.nan]*len(add_list) # flat list of NaNs - # create new list padded with NaNs - nas_to_add_list = [[a]*b for a,b in zip(na_list, add_list)] # nested list of NaNs to add - padded_list = [a + b for a,b in zip(A_list, nas_to_add_list)] # column to explode padded with NaNs - # add padded column to df - df['amino acid mutation alias'] = padded_list + for length_column in ['original mutation description length', 'nucleotide mutation length', 'amino acid mutation length', 'amino acid mutation alias length']: + if not (df[length_column].equals(df['nucleotide position length'])): + column = length_column.replace(' length', '') + #print(column + " and nucleotide position columns are of unequal length") + # now fix it by padding the shorter list with nans + # calculate how many elements to add to each list + df['to_add'] = df['nucleotide position length'] - df[length_column] + # convert columns to lists of lists + A_list = df[column].tolist() # column that needs padding with NaNs, represented as a nested list + add_list = df['to_add'].tolist() # list of integers representing how many elements to add to each list + na_list = [np.nan]*len(add_list) # flat list of NaNs + # create new list padded with NaNs + nas_to_add_list = [[a]*b for a,b in zip(na_list, add_list)] # nested list of NaNs to add + padded_list = [a + b for a,b in zip(A_list, nas_to_add_list)] # column to explode padded with NaNs + # add padded column to df + df[column] = padded_list + #print("Fixed.") # explode list columns df = unnest_multi(df, to_unnest, reset_index=True) From a470b6a65eb529da2893a384e9c9b680cf53b825 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 9 Dec 2024 15:19:21 -0800 Subject: [PATCH 127/161] update scripts --- bin/archive/surveillance_report_pdf.py | 492 +++++++++++++++ bin/surveillance_report_pdf.py | 802 ++++++++++--------------- bin/vcf2gvf.py | 4 +- 3 files changed, 812 insertions(+), 486 deletions(-) create mode 100755 bin/archive/surveillance_report_pdf.py diff --git a/bin/archive/surveillance_report_pdf.py b/bin/archive/surveillance_report_pdf.py new file mode 100755 index 00000000..52e7dff0 --- /dev/null +++ b/bin/archive/surveillance_report_pdf.py @@ -0,0 +1,492 @@ +#!/usr/bin/env python +# -*- coding: utf-8 -*- +""" + +@authors: madeline & zohaib + +This script produces summary of surveillance report in a tex format. +It uses tsv file generated in gvf2tsv as an input and +functional indicator file to produce tex file which can be +used for producing PDF file. + +This script is based on Jared Simpson's code in ncov-tools +https://github.com/jts/ncov-tools/blob/master/workflow/scripts/generate_report.py + +""" + +import argparse +import pandas as pd +import os +import argparse +from datetime import datetime +import glob +import csv +import sys +import re +from collections import OrderedDict +import numpy as np + + +def parse_args(): + parser = argparse.ArgumentParser( + description='Summarizes raw surveillance file (TSV) into ' + 'indicator centric and mutation centric readable ' + 'PDF report') + parser.add_argument('--tsv', type=str, default=None, + help='Path to surveillance report TSV file') + parser.add_argument('--functions_table', type=str, default=None, + help='TSV file containing Pokay ' + 'Functional categories:Indicators ' + 'category mappings') + parser.add_argument('--metadata', type=str, default='n/a', + help='Metadata file for contextual data') + parser.add_argument('--frequency_threshold', type=float, + default=0.25, + help='Alternate frequency threshold cutoff ' + 'for inclusion in report') + parser.add_argument('--virusseq', type=bool, default=False, + help='VirusSeq dataset') + + return parser.parse_args() + + +def summarize_functions(tsv, functions_df_template): + # load functions_df template + df = pd.read_csv(functions_df_template, sep='\t', header=0) + + # populate the Mutations column row by row + for row in df['Sub-categories from POKAY']: + row_mutations_set = set() + # get list of Pokay categories + category_list = row.split(',') + for category in category_list: + # remove trailing spaces to enable matching + category = category.rstrip() + # find mutation names that match that category and add + # them to the set + cat_mutations = tsv[tsv['function_category'] == category][ + 'name'] + cat_mutations_set = set(cat_mutations) + # add category mutations set to row mutations set + row_mutations_set.update(cat_mutations_set) + # save row mutations set in the 'Mutations' column, sorted + # alphabetically + row_list = sorted(list(row_mutations_set)) + row_str = ', '.join(str(e) for e in row_list) + mask = df['Sub-categories from POKAY'] == row + df.loc[mask, 'Mutations'] = row_str + + return df + + +def calculate_frequency(dataframe, newcolname, divisor): + if dataframe['ao'][dataframe['ao'].astype(str).str.contains( + ",")].empty: # if there are no commas anywhere in the 'ao' column, calculate AF straight out + dataframe[newcolname] = dataframe['ao'].astype(int) / dataframe[ + divisor].astype(int) + else: # if there is a comma, add the numbers together to calculate alternate frequency + # tsv_df['added_ao'] = tsv_df['ao'].astype(str).apply(lambda x: sum(map(int, x.split(',')))) + split_series = dataframe['ao'].str.split(pat=',').apply( + pd.Series) + # rename series columns to 'ao_0', 'ao_1', etc. + split_series.columns = ['ao_' + str(name) for name in + split_series.columns.values] + # ensure all counts are numeric + for column in split_series.columns: + split_series[column] = pd.to_numeric(split_series[column], + errors='coerce') + # append series to tsv_df + dataframe = pd.concat([dataframe, split_series], axis=1) + # calculate frequency for each column + colnames = [i for i in dataframe.columns.values.tolist() if + 'ao_' in i] + for column in colnames: + dataframe[column] = dataframe[column] / dataframe[ + divisor].astype(int) + # combine columns into one column + dataframe[newcolname] = dataframe[colnames].apply( + lambda row: ','.join(row.values.astype(str)), axis=1) + # drop split columns + dataframe = dataframe.drop(labels=colnames, axis=1) + dataframe[newcolname] = dataframe[newcolname].str.replace( + ',nan', '') + + return dataframe + + +def add_source_hyperref(dataframe): + dataframe["Citation"] = "\href{" + dataframe["Citation URL"].astype( + str) + "}{" + dataframe["Citation"] + "}" + return dataframe + + +def summarize_mutations(tsv, functions_dataframe): + named_mutations = functions_dataframe['Mutations'].values.tolist() + named_mutations = ', '.join(str(e) for e in named_mutations).split( + ', ') + named_mutations = set(named_mutations) + if metadata != 'n/a': + tsv_df_cols = ['name', 'function_category', + 'function_description', 'viral_lineages', + 'citation', 'ao', 'dp', 'reference_seq', + 'variant_seq', 'citation_url'] + else: + tsv_df_cols = ['name', 'function_category', + 'function_description', + 'citation', 'ao', 'dp', 'reference_seq', + 'variant_seq', 'citation_url'] + + # create empty dataframe + df = pd.DataFrame(columns=tsv_df_cols) + + for mutation in named_mutations: + # get rows of the tsv for that mutation + tsv_rows = tsv[tsv['name'] == mutation] + # keep certain columns of the tsv rows + tsv_rows = tsv_rows[tsv_df_cols] + # concatenate dfs + df = pd.concat((df, tsv_rows)) + + # remove clade-defining values from strains column + # renaming 'viral_clade_defining' to 'viral_lineages' + if metadata != 'n/a': + df['viral_lineages'] = df[ + 'viral_lineages'].str.replace(r"=.*?;", ",", regex=True) + # remove trailing commas + df['viral_lineages'] = df[ + 'viral_lineages'].str.rstrip(' ').str.rstrip(',') + + # rename mutations_df columns + # Removing 'Frequency (Variant)' for now + # Renaming 'dp' to 'sequence_depth' + final_mutations_df_cols = ['Mutations', 'Sub-category', + 'Function', 'Lineages', 'Citation', + 'Alternate Allele Obs', + 'Sequence Depth', 'Reference Allele', + 'Alternate Allele', 'Citation URL'] + else: + final_mutations_df_cols = ['Mutations', 'Sub-category', + 'Function', 'Citation', + 'Alternate Allele Obs', + 'Sequence Depth', 'Reference Allele', + 'Alternate Allele', 'Citation URL'] + renaming_dict = dict(zip(tsv_df_cols, final_mutations_df_cols)) + df = df.rename(columns=renaming_dict) + + # add 'Frequency (Functional)' column + # adding if condition + # if there are no commas + # anywhere in the 'ao' column, calculate AF straight out + #if df['Alternate Allele Obs'][df['Alternate Allele Obs'].astype( + # str).str.contains("n/a")].empty: + # df['Alternate Frequency'] = np.nan + if df['Alternate Allele Obs'][df['Alternate Allele Obs'].astype( + str).str.contains(",")].empty: + df['Alternate Frequency'] = round( + df['Alternate Allele Obs'].astype( + int) / df['Sequence Depth'].astype(int), 2) + else: + # if there is a comma, add the numbers together to calculate + # alternate frequency tsv_df['added_ao'] = tsv_df[ + # 'ao'].astype(str).apply(lambda x: sum(map(int, x.split(', + # ')))) + df['Agg Alternate Allele'] = df['Alternate Allele Obs'].apply( + lambda x: sum(map(int, x.split(',')))) + # rename series columns to 'ao_0', 'ao_1', etc. + df['Alternate Frequency'] = round(df['Agg Alternate ' \ + 'Allele'].astype( + int) / df['Sequence Depth'].astype(int), 2) + + df = add_source_hyperref(dataframe=df) + if not df['Alternate Frequency'].isnull().values.any(): + mask = df['Alternate Frequency'] >= args.frequency_threshold + df = df[mask] + if metadata != 'n/a': + mutations_df_cols = ['Mutations', 'Sub-category', + 'Function', 'Lineages', 'Citation', + 'Sequence Depth', 'Reference Allele', + 'Alternate Allele', + 'Alternate Frequency'] + else: + mutations_df_cols = ['Mutations', 'Sub-category', + 'Function', 'Citation', + 'Sequence Depth', 'Reference Allele', + 'Alternate Allele', 'Alternate Frequency'] + df = df[mutations_df_cols] + return df + + +# +# utility class to assist in converting +# a tsv into a latex table - it can +# rename header columns (name_map) +# perform arbitrary transforms (row_func) +# and filter out columns/rows +# + + +class TableFormatter: + def __init__(self): + self.name_map = dict() + self.row_func = dict() + self.column_filter = dict() + self.row_accept = None + self.table_spec = "" + self.size = "normalsize" + + +# latex starting boilerplate to set up the document class, packages, etc +def write_preamble(): + p = r''' +\documentclass{article} +\usepackage[margin=0.5in, right=1.125in, footskip=35pt]{geometry} +\usepackage{fancyheadings} + +\usepackage{lastpage} +\pagestyle{fancy} +\usepackage{hyperref} +\usepackage[utf8]{inputenc} +\usepackage{graphicx} +\usepackage{array} +\usepackage{float} +\usepackage{microtype} +\pagestyle{fancy} +\geometry{textwidth=6.0in} + + +\lhead{\small + \vspace{-2.0\baselineskip}\href{ + https://github.com/cidgoh/nf-ncov-voc}{nf-ncov-voc}} +\rhead{\small + \vspace{-2.0\baselineskip}\thepage\ of \pageref{LastPage}} +\cfoot{\small + \vspace{-2.0\baselineskip}\href{mailto:mzanwar@sfu.ca}{ + Contact Us}} +\rfoot{\small + \vspace{-2.0\baselineskip}CIDGOH\textsuperscript{ + \textcopyright}} +\renewcommand{\footrulewidth}{1pt}% default is 0pt + + +\usepackage{longtable} + +\newcolumntype{C}[1]{>{\centering\let\newline\\\arraybackslash\hspace{0pt}}m{#1}} + +\emergencystretch 3em + + +\begin{document} + + + +''' + print(p) + + +# latex ending boilerplate +def write_postamble(): + p = r''' +\end{document}''' + print(p) + + +# count the number of rows in a tsv file +def count_tsv(filename): + c = 0 + with(open(filename)) as f: + reader = csv.DictReader(f, delimiter="\t") + for row in reader: + c += 1 + return c + + +def escape_latex(s): + s = s.replace("_", "\_") + s = s.replace("&", "\&") + s = s.replace("%", "\%") + s = s.replace("#", "\#") + s = s.replace("$", "\$") + if not "href" in s: + s = s.replace("{", "\{") + s = s.replace("}", "\}") + s = s.replace("~", "\textasciitilde") + s = s.replace("^", "\textasciicircum}") + return s + + +# high-level function to transform a tsv into a latex table +# performing remapping of column names and arbitrary transformation +# of values within each column (e.g. escaping characters latex +# doesn't like) using table formatter +def df_to_table(df, table_formatter): + reader = df.to_dict(into=OrderedDict, orient='records') + + rows = list() + header = list() + + for row in reader: + + # remove columns + for k in table_formatter.column_filter: + del row[k] + + # skip rows that fail the row filter, if any + if table_formatter.row_accept is not None and not \ + table_formatter.row_accept( + row): + continue + + if len(header) == 0: + + # remap column names + for k in row.keys(): + if k in table_formatter.name_map: + header.append(table_formatter.name_map[k]) + else: + header.append(escape_latex(k)) + + # transform with row func + for k in row: + if k in table_formatter.row_func: + row[k] = table_formatter.row_func[k](row[k]) + rows.append(row.values()) + + # write latex to stdout + write_table(table_formatter.table_spec, header, rows, + table_formatter.size) + + +# latex for displaying a table +def write_table(spec, header, rows, size): + # print(r"\begin{center}") + print(r"\%s" % size) + + print(r"\begin{longtable}{%s}" % spec) + + print(r"\hline") + print(" & ".join(header) + r" \\ \hline") + print(r"\endhead") + for r in rows: + print(" & ".join( + [escape_latex(str(v)) for v in r]) + r" \\ \hline") + + print(r"\end{longtable}") + print(r"\normalsize") + # print(r"\end{center}") + + +# write the large per-sample QC table +def write_func_summary(df): + tf = TableFormatter() + tf.size = "scriptsize" + tf.table_spec = "{|p{4.0cm}|p{7.0cm}|p{5.0cm}|}" + + print(r"\section*{Indicator}") + print( + r"This table contains key indicators " + r"identified") + df_to_table(df, tf) + + +def write_mutation_summary(df): + tf = TableFormatter() + tf.size = "scriptsize" + if metadata != 'n/a': + tf.table_spec = "{|p{1.2cm}|p{2.5cm}|p{3.3cm}|p{1.8cm}|p{1.5cm}|p{1.0cm}|p{1.6cm}|p{1.3cm}|p{1.3cm}|}" + else: + tf.table_spec = "{|p{1.2cm}|p{2.5cm}|p{3.3cm}|p{1.8cm}|p{1.0cm}|p{1.3cm}|p{1.3cm}|p{1.3cm}|}" + + print(r"\section*{Mutation Significance}") + print( + r"This table contains key functional impacts of mutations " + r"identified") + df_to_table(df, tf) + + +if __name__ == '__main__': + + args = parse_args() + functions_template = args.functions_table + report_tsv = args.tsv + metadata = args.metadata + tsv_df = pd.read_csv(report_tsv, sep='\t', header=0) + + if metadata != 'n/a': + metadata_df = pd.read_csv(metadata, sep="\t", low_memory=False, compression='gzip', + parse_dates=[ + 'sample_collection_date']) + + metadata_df['sample_collection_date'] = pd.to_datetime( + metadata_df['sample_collection_date'], format='%Y-%m-%d', + errors='coerce') + lineages = [] + for lineage in tsv_df['viral_lineages']: + lineage = lineage.split(", ") + lineages.extend(lineage) + + base = os.path.basename(args.tsv) + variant = base.split('_')[0] + # make functions_df + functions_df = summarize_functions(tsv=tsv_df, + functions_df_template= + functions_template) + + # make mutations_df + mutations_df = summarize_mutations(tsv=tsv_df, + functions_dataframe=functions_df) + write_preamble() + + print(r"\section*{Surveillance report}") + print( + r"Surveillance generated by nf-ncov-voc for %s variant" % ( + variant)) + + print(r"\subsection*{Date }") + print( + r"This report is generated on %s using %s number of genomes collected between %s and %s " + % ( + datetime.today().strftime('%Y-%m-%d'), + len(metadata_df.index), + pd.to_datetime(metadata_df['sample_collection_date'].min()).date(), + pd.to_datetime(metadata_df['sample_collection_date'].max()).date())) + + print(r"\section*{Pango Lineages}") + print(r"{Pango Lineages in this report }%s " + % sorted(set(lineages))) + write_func_summary(df=functions_df) + write_mutation_summary(df=mutations_df) + + if args.virusseq is True: + print(r"\newpage") + print("The results here are in whole or " + "part based upon data hosted at the " + "Canadian VirusSeq Data Portal: " + " \href{https://virusseq-dataportal.ca/}{" + "https://virusseq-dataportal.ca/}." + "We wish to acknowledge the following " + "organisations/laboratories for " + "contributing data to the Portal: " + "Canadian Public Health Laboratory " + "Network (CPHLN), CanCOGGeN VirusSeq " + "and the list of labs available at " + "\href{https://virusseq-dataportal.ca/acknowledgements" + "}{https://virusseq-dataportal.ca/acknowledgements})") + + write_postamble() + + # mutations_df.to_csv('mutations.tsv', sep='\t', index=False) + else: + # base = os.path.basename(args.tsv) + # variant = base.split('_')[0] + # make functions_df + functions_df = summarize_functions(tsv=tsv_df, + functions_df_template= + functions_template) + # make mutations_df + mutations_df = summarize_mutations(tsv=tsv_df, + functions_dataframe=functions_df) + write_preamble() + print(r"\section*{Surveillance report}") + write_func_summary(df=functions_df) + write_mutation_summary(df=mutations_df) + write_postamble() diff --git a/bin/surveillance_report_pdf.py b/bin/surveillance_report_pdf.py index 52e7dff0..b1984e8f 100755 --- a/bin/surveillance_report_pdf.py +++ b/bin/surveillance_report_pdf.py @@ -1,492 +1,326 @@ -#!/usr/bin/env python +#!/usr/bin/env python3 # -*- coding: utf-8 -*- -""" -@authors: madeline & zohaib - -This script produces summary of surveillance report in a tex format. -It uses tsv file generated in gvf2tsv as an input and -functional indicator file to produce tex file which can be -used for producing PDF file. - -This script is based on Jared Simpson's code in ncov-tools -https://github.com/jts/ncov-tools/blob/master/workflow/scripts/generate_report.py - -""" - -import argparse +from reportlab.lib.styles import ParagraphStyle, getSampleStyleSheet +from reportlab.platypus import Paragraph, Spacer, SimpleDocTemplate, PageBreak, Table, TableStyle +from reportlab.lib import colors +from reportlab.lib.pagesizes import letter, landscape +from reportlab.lib.units import inch +from reportlab.lib.enums import TA_JUSTIFY, TA_LEFT, TA_CENTER import pandas as pd -import os -import argparse +from collections import defaultdict from datetime import datetime -import glob -import csv -import sys -import re -from collections import OrderedDict -import numpy as np - - -def parse_args(): - parser = argparse.ArgumentParser( - description='Summarizes raw surveillance file (TSV) into ' - 'indicator centric and mutation centric readable ' - 'PDF report') - parser.add_argument('--tsv', type=str, default=None, - help='Path to surveillance report TSV file') - parser.add_argument('--functions_table', type=str, default=None, - help='TSV file containing Pokay ' - 'Functional categories:Indicators ' - 'category mappings') - parser.add_argument('--metadata', type=str, default='n/a', - help='Metadata file for contextual data') - parser.add_argument('--frequency_threshold', type=float, - default=0.25, - help='Alternate frequency threshold cutoff ' - 'for inclusion in report') - parser.add_argument('--virusseq', type=bool, default=False, - help='VirusSeq dataset') - - return parser.parse_args() - - -def summarize_functions(tsv, functions_df_template): - # load functions_df template - df = pd.read_csv(functions_df_template, sep='\t', header=0) - - # populate the Mutations column row by row - for row in df['Sub-categories from POKAY']: - row_mutations_set = set() - # get list of Pokay categories - category_list = row.split(',') - for category in category_list: - # remove trailing spaces to enable matching - category = category.rstrip() - # find mutation names that match that category and add - # them to the set - cat_mutations = tsv[tsv['function_category'] == category][ - 'name'] - cat_mutations_set = set(cat_mutations) - # add category mutations set to row mutations set - row_mutations_set.update(cat_mutations_set) - # save row mutations set in the 'Mutations' column, sorted - # alphabetically - row_list = sorted(list(row_mutations_set)) - row_str = ', '.join(str(e) for e in row_list) - mask = df['Sub-categories from POKAY'] == row - df.loc[mask, 'Mutations'] = row_str - - return df - - -def calculate_frequency(dataframe, newcolname, divisor): - if dataframe['ao'][dataframe['ao'].astype(str).str.contains( - ",")].empty: # if there are no commas anywhere in the 'ao' column, calculate AF straight out - dataframe[newcolname] = dataframe['ao'].astype(int) / dataframe[ - divisor].astype(int) - else: # if there is a comma, add the numbers together to calculate alternate frequency - # tsv_df['added_ao'] = tsv_df['ao'].astype(str).apply(lambda x: sum(map(int, x.split(',')))) - split_series = dataframe['ao'].str.split(pat=',').apply( - pd.Series) - # rename series columns to 'ao_0', 'ao_1', etc. - split_series.columns = ['ao_' + str(name) for name in - split_series.columns.values] - # ensure all counts are numeric - for column in split_series.columns: - split_series[column] = pd.to_numeric(split_series[column], - errors='coerce') - # append series to tsv_df - dataframe = pd.concat([dataframe, split_series], axis=1) - # calculate frequency for each column - colnames = [i for i in dataframe.columns.values.tolist() if - 'ao_' in i] - for column in colnames: - dataframe[column] = dataframe[column] / dataframe[ - divisor].astype(int) - # combine columns into one column - dataframe[newcolname] = dataframe[colnames].apply( - lambda row: ','.join(row.values.astype(str)), axis=1) - # drop split columns - dataframe = dataframe.drop(labels=colnames, axis=1) - dataframe[newcolname] = dataframe[newcolname].str.replace( - ',nan', '') - - return dataframe - - -def add_source_hyperref(dataframe): - dataframe["Citation"] = "\href{" + dataframe["Citation URL"].astype( - str) + "}{" + dataframe["Citation"] + "}" - return dataframe - - -def summarize_mutations(tsv, functions_dataframe): - named_mutations = functions_dataframe['Mutations'].values.tolist() - named_mutations = ', '.join(str(e) for e in named_mutations).split( - ', ') - named_mutations = set(named_mutations) - if metadata != 'n/a': - tsv_df_cols = ['name', 'function_category', - 'function_description', 'viral_lineages', - 'citation', 'ao', 'dp', 'reference_seq', - 'variant_seq', 'citation_url'] - else: - tsv_df_cols = ['name', 'function_category', - 'function_description', - 'citation', 'ao', 'dp', 'reference_seq', - 'variant_seq', 'citation_url'] - - # create empty dataframe - df = pd.DataFrame(columns=tsv_df_cols) - - for mutation in named_mutations: - # get rows of the tsv for that mutation - tsv_rows = tsv[tsv['name'] == mutation] - # keep certain columns of the tsv rows - tsv_rows = tsv_rows[tsv_df_cols] - # concatenate dfs - df = pd.concat((df, tsv_rows)) - - # remove clade-defining values from strains column - # renaming 'viral_clade_defining' to 'viral_lineages' - if metadata != 'n/a': - df['viral_lineages'] = df[ - 'viral_lineages'].str.replace(r"=.*?;", ",", regex=True) - # remove trailing commas - df['viral_lineages'] = df[ - 'viral_lineages'].str.rstrip(' ').str.rstrip(',') - - # rename mutations_df columns - # Removing 'Frequency (Variant)' for now - # Renaming 'dp' to 'sequence_depth' - final_mutations_df_cols = ['Mutations', 'Sub-category', - 'Function', 'Lineages', 'Citation', - 'Alternate Allele Obs', - 'Sequence Depth', 'Reference Allele', - 'Alternate Allele', 'Citation URL'] - else: - final_mutations_df_cols = ['Mutations', 'Sub-category', - 'Function', 'Citation', - 'Alternate Allele Obs', - 'Sequence Depth', 'Reference Allele', - 'Alternate Allele', 'Citation URL'] - renaming_dict = dict(zip(tsv_df_cols, final_mutations_df_cols)) - df = df.rename(columns=renaming_dict) - - # add 'Frequency (Functional)' column - # adding if condition - # if there are no commas - # anywhere in the 'ao' column, calculate AF straight out - #if df['Alternate Allele Obs'][df['Alternate Allele Obs'].astype( - # str).str.contains("n/a")].empty: - # df['Alternate Frequency'] = np.nan - if df['Alternate Allele Obs'][df['Alternate Allele Obs'].astype( - str).str.contains(",")].empty: - df['Alternate Frequency'] = round( - df['Alternate Allele Obs'].astype( - int) / df['Sequence Depth'].astype(int), 2) - else: - # if there is a comma, add the numbers together to calculate - # alternate frequency tsv_df['added_ao'] = tsv_df[ - # 'ao'].astype(str).apply(lambda x: sum(map(int, x.split(', - # ')))) - df['Agg Alternate Allele'] = df['Alternate Allele Obs'].apply( - lambda x: sum(map(int, x.split(',')))) - # rename series columns to 'ao_0', 'ao_1', etc. - df['Alternate Frequency'] = round(df['Agg Alternate ' \ - 'Allele'].astype( - int) / df['Sequence Depth'].astype(int), 2) - - df = add_source_hyperref(dataframe=df) - if not df['Alternate Frequency'].isnull().values.any(): - mask = df['Alternate Frequency'] >= args.frequency_threshold - df = df[mask] - if metadata != 'n/a': - mutations_df_cols = ['Mutations', 'Sub-category', - 'Function', 'Lineages', 'Citation', - 'Sequence Depth', 'Reference Allele', - 'Alternate Allele', - 'Alternate Frequency'] - else: - mutations_df_cols = ['Mutations', 'Sub-category', - 'Function', 'Citation', - 'Sequence Depth', 'Reference Allele', - 'Alternate Allele', 'Alternate Frequency'] - df = df[mutations_df_cols] - return df - - -# -# utility class to assist in converting -# a tsv into a latex table - it can -# rename header columns (name_map) -# perform arbitrary transforms (row_func) -# and filter out columns/rows -# - - -class TableFormatter: - def __init__(self): - self.name_map = dict() - self.row_func = dict() - self.column_filter = dict() - self.row_accept = None - self.table_spec = "" - self.size = "normalsize" - - -# latex starting boilerplate to set up the document class, packages, etc -def write_preamble(): - p = r''' -\documentclass{article} -\usepackage[margin=0.5in, right=1.125in, footskip=35pt]{geometry} -\usepackage{fancyheadings} - -\usepackage{lastpage} -\pagestyle{fancy} -\usepackage{hyperref} -\usepackage[utf8]{inputenc} -\usepackage{graphicx} -\usepackage{array} -\usepackage{float} -\usepackage{microtype} -\pagestyle{fancy} -\geometry{textwidth=6.0in} - - -\lhead{\small - \vspace{-2.0\baselineskip}\href{ - https://github.com/cidgoh/nf-ncov-voc}{nf-ncov-voc}} -\rhead{\small - \vspace{-2.0\baselineskip}\thepage\ of \pageref{LastPage}} -\cfoot{\small - \vspace{-2.0\baselineskip}\href{mailto:mzanwar@sfu.ca}{ - Contact Us}} -\rfoot{\small - \vspace{-2.0\baselineskip}CIDGOH\textsuperscript{ - \textcopyright}} -\renewcommand{\footrulewidth}{1pt}% default is 0pt - - -\usepackage{longtable} - -\newcolumntype{C}[1]{>{\centering\let\newline\\\arraybackslash\hspace{0pt}}m{#1}} - -\emergencystretch 3em - - -\begin{document} - - - -''' - print(p) - - -# latex ending boilerplate -def write_postamble(): - p = r''' -\end{document}''' - print(p) - - -# count the number of rows in a tsv file -def count_tsv(filename): - c = 0 - with(open(filename)) as f: - reader = csv.DictReader(f, delimiter="\t") - for row in reader: - c += 1 - return c - - -def escape_latex(s): - s = s.replace("_", "\_") - s = s.replace("&", "\&") - s = s.replace("%", "\%") - s = s.replace("#", "\#") - s = s.replace("$", "\$") - if not "href" in s: - s = s.replace("{", "\{") - s = s.replace("}", "\}") - s = s.replace("~", "\textasciitilde") - s = s.replace("^", "\textasciicircum}") - return s - - -# high-level function to transform a tsv into a latex table -# performing remapping of column names and arbitrary transformation -# of values within each column (e.g. escaping characters latex -# doesn't like) using table formatter -def df_to_table(df, table_formatter): - reader = df.to_dict(into=OrderedDict, orient='records') - - rows = list() - header = list() - - for row in reader: - - # remove columns - for k in table_formatter.column_filter: - del row[k] - - # skip rows that fail the row filter, if any - if table_formatter.row_accept is not None and not \ - table_formatter.row_accept( - row): - continue - - if len(header) == 0: - - # remap column names - for k in row.keys(): - if k in table_formatter.name_map: - header.append(table_formatter.name_map[k]) - else: - header.append(escape_latex(k)) - - # transform with row func - for k in row: - if k in table_formatter.row_func: - row[k] = table_formatter.row_func[k](row[k]) - rows.append(row.values()) - - # write latex to stdout - write_table(table_formatter.table_spec, header, rows, - table_formatter.size) - - -# latex for displaying a table -def write_table(spec, header, rows, size): - # print(r"\begin{center}") - print(r"\%s" % size) - - print(r"\begin{longtable}{%s}" % spec) - - print(r"\hline") - print(" & ".join(header) + r" \\ \hline") - print(r"\endhead") - for r in rows: - print(" & ".join( - [escape_latex(str(v)) for v in r]) + r" \\ \hline") - - print(r"\end{longtable}") - print(r"\normalsize") - # print(r"\end{center}") - - -# write the large per-sample QC table -def write_func_summary(df): - tf = TableFormatter() - tf.size = "scriptsize" - tf.table_spec = "{|p{4.0cm}|p{7.0cm}|p{5.0cm}|}" - - print(r"\section*{Indicator}") - print( - r"This table contains key indicators " - r"identified") - df_to_table(df, tf) - - -def write_mutation_summary(df): - tf = TableFormatter() - tf.size = "scriptsize" - if metadata != 'n/a': - tf.table_spec = "{|p{1.2cm}|p{2.5cm}|p{3.3cm}|p{1.8cm}|p{1.5cm}|p{1.0cm}|p{1.6cm}|p{1.3cm}|p{1.3cm}|}" - else: - tf.table_spec = "{|p{1.2cm}|p{2.5cm}|p{3.3cm}|p{1.8cm}|p{1.0cm}|p{1.3cm}|p{1.3cm}|p{1.3cm}|}" - - print(r"\section*{Mutation Significance}") - print( - r"This table contains key functional impacts of mutations " - r"identified") - df_to_table(df, tf) - - -if __name__ == '__main__': - - args = parse_args() - functions_template = args.functions_table - report_tsv = args.tsv - metadata = args.metadata - tsv_df = pd.read_csv(report_tsv, sep='\t', header=0) +import argparse - if metadata != 'n/a': - metadata_df = pd.read_csv(metadata, sep="\t", low_memory=False, compression='gzip', - parse_dates=[ - 'sample_collection_date']) +def get_unique_non_na_value(df, column_name): + """Get the unique non-N/A value from a column, or return 'Unknown' if not found.""" + unique_values = df[column_name].dropna().unique() + return unique_values[0] if len(unique_values) == 1 else "Multiple values" if len(unique_values) > 1 else "Unknown" + +def generate_metadata_section(tsv_df, metadata_file=None): + """Generates metadata text from the TSV file and optional metadata file.""" + styles = getSampleStyleSheet() + + # Create custom styles + title_style = ParagraphStyle( + 'TitleStyle', + parent=styles['Heading1'], + fontSize=16, + alignment=TA_CENTER, + spaceAfter=12 + ) + heading_style = ParagraphStyle( + 'HeadingStyle', + parent=styles['Heading2'], + fontSize=12, + spaceBefore=6, + spaceAfter=6 + ) + normal_style = ParagraphStyle( + 'NormalStyle', + parent=styles['Normal'], + fontSize=10, + spaceBefore=3, + spaceAfter=3 + ) + + # Get the lineage/clade, organism, reference accession, and reference database name + lineage_clade = get_unique_non_na_value(tsv_df, 'clade') + organism = get_unique_non_na_value(tsv_df, 'organism') + ref_accession = get_unique_non_na_value(tsv_df, 'reference_accession') + ref_db_name = get_unique_non_na_value(tsv_df, 'reference_database_name') + + report_date = datetime.today().strftime('%Y-%m-%d') + + if metadata_file: + metadata_df = pd.read_csv(metadata_file, sep="\t", low_memory=False, compression='gzip') metadata_df['sample_collection_date'] = pd.to_datetime( - metadata_df['sample_collection_date'], format='%Y-%m-%d', - errors='coerce') - lineages = [] - for lineage in tsv_df['viral_lineages']: - lineage = lineage.split(", ") - lineages.extend(lineage) - - base = os.path.basename(args.tsv) - variant = base.split('_')[0] - # make functions_df - functions_df = summarize_functions(tsv=tsv_df, - functions_df_template= - functions_template) - - # make mutations_df - mutations_df = summarize_mutations(tsv=tsv_df, - functions_dataframe=functions_df) - write_preamble() - - print(r"\section*{Surveillance report}") - print( - r"Surveillance generated by nf-ncov-voc for %s variant" % ( - variant)) - - print(r"\subsection*{Date }") - print( - r"This report is generated on %s using %s number of genomes collected between %s and %s " - % ( - datetime.today().strftime('%Y-%m-%d'), - len(metadata_df.index), - pd.to_datetime(metadata_df['sample_collection_date'].min()).date(), - pd.to_datetime(metadata_df['sample_collection_date'].max()).date())) - - print(r"\section*{Pango Lineages}") - print(r"{Pango Lineages in this report }%s " - % sorted(set(lineages))) - write_func_summary(df=functions_df) - write_mutation_summary(df=mutations_df) - - if args.virusseq is True: - print(r"\newpage") - print("The results here are in whole or " - "part based upon data hosted at the " - "Canadian VirusSeq Data Portal: " - " \href{https://virusseq-dataportal.ca/}{" - "https://virusseq-dataportal.ca/}." - "We wish to acknowledge the following " - "organisations/laboratories for " - "contributing data to the Portal: " - "Canadian Public Health Laboratory " - "Network (CPHLN), CanCOGGeN VirusSeq " - "and the list of labs available at " - "\href{https://virusseq-dataportal.ca/acknowledgements" - "}{https://virusseq-dataportal.ca/acknowledgements})") - - write_postamble() - - # mutations_df.to_csv('mutations.tsv', sep='\t', index=False) + metadata_df['sample_collection_date'], format='%Y-%m-%d', errors='coerce' + ) + start_date = metadata_df['sample_collection_date'].min().date() + end_date = metadata_df['sample_collection_date'].max().date() + num_genomes = len(metadata_df) + + genome_info = f"using {num_genomes} number of genomes collected between {start_date} and {end_date}" else: - # base = os.path.basename(args.tsv) - # variant = base.split('_')[0] - # make functions_df - functions_df = summarize_functions(tsv=tsv_df, - functions_df_template= - functions_template) - # make mutations_df - mutations_df = summarize_mutations(tsv=tsv_df, - functions_dataframe=functions_df) - write_preamble() - print(r"\section*{Surveillance report}") - write_func_summary(df=functions_df) - write_mutation_summary(df=mutations_df) - write_postamble() + genome_info = "genome collection information not available" + + elements = [ + Paragraph("Surveillance Report", title_style), + Paragraph("Report Details", heading_style), + Paragraph(f"Surveillance generated by nf-ncov-voc for lineage/clade: {lineage_clade}", normal_style), + Paragraph(f"This report is generated on {report_date} {genome_info}", normal_style), + Spacer(1, 12), + Paragraph("Additional Information", heading_style), + Paragraph(f"Organism: {organism}", normal_style), + Paragraph(f"Reference Accession: {ref_accession}", normal_style), + Paragraph(f"Reference Database Name: {ref_db_name}", normal_style), + ] + + return elements + + +def wrap_text_in_cell(cell, style): + if isinstance(cell, str): + return Paragraph(cell, style) + return cell + +def generate_first_table(tsv_df, indicator_mapping_df, styles): + """Generates the first table: Indicator Summary.""" + def get_mutations_by_category(tsv_df, categories): + mutations_by_category = defaultdict(set) + for category in categories.split(','): + category = category.strip() + mutations = tsv_df.loc[tsv_df['measured_variant_functional_effect'] == category, 'original_mutation_description'] + mutations_by_category[category].update(mutations) + return ', '.join(sorted({m for ms in mutations_by_category.values() for m in ms})) + + first_table_data = [["Surveillance Indicator", "Functional Categories", "Mutations"]] + for _, row in indicator_mapping_df.iterrows(): + mutations = get_mutations_by_category(tsv_df, row["Sub-categories from POKAY"]) + first_table_data.append([row["Indicator"], row["Sub-categories from POKAY"], mutations]) + + wrapped_style = ParagraphStyle( + name="Wrapped", + parent=styles["Normal"], + fontSize=8, + leading=10, + wordWrap='CJK', + alignment=TA_LEFT + ) + + wrapped_data = [[wrap_text_in_cell(cell, wrapped_style) for cell in row] for row in first_table_data] + + first_table = Table(wrapped_data, colWidths=[2 * inch, 2.5 * inch, 4 * inch]) + first_table.setStyle(TableStyle([ + ('BACKGROUND', (0, 0), (-1, 0), colors.grey), + ('TEXTCOLOR', (0, 0), (-1, 0), colors.whitesmoke), + ('ALIGN', (0, 0), (-1, -1), 'LEFT'), + ('VALIGN', (0, 0), (-1, -1), 'TOP'), + ('GRID', (0, 0), (-1, -1), 1, colors.black), + ('FONTNAME', (0, 0), (-1, 0), 'Helvetica-Bold'), + ('FONTNAME', (0, 1), (-1, -1), 'Helvetica'), + ('FONTSIZE', (0, 0), (-1, -1), 8), + ('BOTTOMPADDING', (0, 0), (-1, -1), 6), + ('TOPPADDING', (0, 0), (-1, -1), 6), + ])) + description = "This table contains key indicators identified" + return create_paginated_table(first_table_data, styles, "Table 1: Indicator Summary", description) + + +def generate_second_table(tsv_df, styles): + """Generates the second table with unique mutation details.""" + columns = { + "Mutations": "original_mutation_description", + "Functional Category": "measured_variant_functional_effect", + "Annotation Resource": "functional_annotation_resource", + "Lineages": "viral_lineages", + "Clade": "clade", + "Sequence Depth": "dp", + "Reference Allele": "reference_seq", + "Alternate Allele": "variant_seq", + "Alternate Frequency": "alternate_frequency" + } + + # Filter out columns with all NaN values + valid_columns = {k: v for k, v in columns.items() if not tsv_df[v].isna().all()} + + # Prepare data + data = [list(valid_columns.keys())] # Add headers + + # Create a temporary dataframe with only the columns we need + temp_df = tsv_df.dropna(subset=["measured_variant_functional_effect"]) + temp_df = temp_df[[v for v in valid_columns.values()]] + + # Round the alternate_frequency to 3 decimal places + temp_df['alternate_frequency'] = temp_df['alternate_frequency'].apply(lambda x: round(float(x), 3) if pd.notnull(x) else "N/A") + + # Remove duplicates + temp_df = temp_df.drop_duplicates() + + # Convert dataframe to list of lists + for _, row in temp_df.iterrows(): + data.append([row[v] for v in valid_columns.values()]) + + description = "This table contains key functional impacts of mutations identified" + return create_paginated_table(data, styles, "Table 2: Mutation Details Summary", description) + +def generate_third_table(tsv_df, styles): + """Generates the third table with functional effects, including publication year and citation.""" + columns = { + "Mutations": "original_mutation_description", + "Functional Category": "measured_variant_functional_effect", + "Annotation Resource": "functional_annotation_resource", + "Functional Effect": "variant_functional_effect_description", + "Publication Year": "publication_year", + "Citation": "citation", + "URL": "url" # We'll use this to create the hyperlink + } + + data = [list(columns.keys())[:-1]] # Add headers, excluding the URL column + + # Create a custom style for the hyperlink + link_style = ParagraphStyle( + 'LinkStyle', + parent=styles['Normal'], + fontSize=8, + textColor='blue' + ) + + for _, row in tsv_df.dropna(subset=["measured_variant_functional_effect"]).iterrows(): + row_data = [] + for key, col in columns.items(): + if key == "Citation": + # Create a hyperlink for the citation using HTML-style link + url = row.get(columns["URL"], "") + citation_text = row.get(col, "") + if url and citation_text: + link_text = f'{citation_text}' + paragraph = Paragraph(link_text, link_style) + row_data.append(paragraph) + else: + row_data.append(citation_text) + elif key == "Publication Year": + # Convert publication year to integer and then to string + year = row.get(col) + if pd.notna(year): + year_str = str(int(year)) + else: + year_str = "" + row_data.append(year_str) + elif key != "URL": # Skip the URL column in the final table + row_data.append(row.get(col, "")) + data.append(row_data) + + description = "This table contains detailed functional descriptions of each functional category" + + # Adjust column widths to accommodate new columns + col_widths = [1.5*inch, 1.5*inch, 1.5*inch, 2*inch, 1*inch, 2*inch] + + return create_paginated_table(data, styles, "Table 3: Functional Effect Summary", description, col_widths=col_widths) + +def create_paginated_table(data, styles, title, description=None, max_width=9*inch, col_widths=None): + """Creates a table that can split across pages automatically with text wrapping.""" + + def wrap_text(cell, width): + if isinstance(cell, str): + return Paragraph(cell, ParagraphStyle( + name="Wrapped", + parent=styles["Normal"], + fontSize=8, + leading=10, + wordWrap='CJK', + alignment=TA_LEFT + )) + return cell + + col_widths = col_widths or [max_width / len(data[0])] * len(data[0]) + wrapped_data = [[wrap_text(cell, col_widths[i]) for i, cell in enumerate(row)] for row in data] + + table = Table(wrapped_data, colWidths=col_widths, repeatRows=1) + table.setStyle(TableStyle([ + ('BACKGROUND', (0, 0), (-1, 0), colors.grey), + ('TEXTCOLOR', (0, 0), (-1, 0), colors.whitesmoke), + ('ALIGN', (0, 0), (-1, -1), 'LEFT'), + ('VALIGN', (0, 0), (-1, -1), 'TOP'), + ('GRID', (0, 0), (-1, -1), 1, colors.black), + ('FONTNAME', (0, 0), (-1, 0), 'Helvetica-Bold'), + ('FONTNAME', (0, 1), (-1, -1), 'Helvetica'), + ('FONTSIZE', (0, 0), (-1, -1), 8), + ('BOTTOMPADDING', (0, 0), (-1, -1), 6), + ('TOPPADDING', (0, 0), (-1, -1), 6), + ])) + + elements = [] + elements.append(Paragraph(title, styles["Heading2"])) + if description: + elements.append(Paragraph(description, styles["Normal"])) + elements.append(table) + elements.append(PageBreak()) + + return elements + +def generate_pdf(tsv_file, output_pdf, metadata_file=None, indicator_mapping=None, args=None): + """Main function to generate the PDF with table descriptions and VirusSeq acknowledgment.""" + tsv_df = pd.read_csv(tsv_file, sep='\t', header=0) + metadata_elements = generate_metadata_section(tsv_df, metadata_file) + indicator_mapping_df = pd.read_csv(indicator_mapping, sep='\t', header=0) + styles = getSampleStyleSheet() + + # Initialize PDF + pdf = SimpleDocTemplate(output_pdf, pagesize=landscape(letter), + topMargin=0.5*inch, bottomMargin=0.5*inch, + leftMargin=0.5*inch, rightMargin=0.5*inch) + elements = [] + + # Add metadata section + elements.extend(metadata_elements) + elements.append(PageBreak()) + + try: + # Add tables + elements.extend(generate_first_table(tsv_df, indicator_mapping_df, styles)) + elements.extend(generate_second_table(tsv_df, styles)) + elements.extend(generate_third_table(tsv_df, styles)) + + # Add VirusSeq acknowledgment if args.virusseq is True + if args and args.virusseq: + elements.append(PageBreak()) + virusseq_style = ParagraphStyle( + 'VirusSeqAcknowledgment', + parent=styles['Normal'], + fontSize=8, + leading=10, + alignment=TA_JUSTIFY + ) + virusseq_text = ( + "The results here are in whole or part based upon data hosted at the " + "Canadian VirusSeq Data Portal: " + "https://virusseq-dataportal.ca/. " + "We wish to acknowledge the following organisations/laboratories for " + "contributing data to the Portal: Canadian Public Health Laboratory " + "Network (CPHLN), CanCOGGeN VirusSeq and the list of labs available at " + "" + "https://virusseq-dataportal.ca/acknowledgements." + ) + elements.append(Paragraph(virusseq_text, virusseq_style)) + + # Build PDF + pdf.build(elements) + except Exception as e: + print(f"Error generating PDF: {e}") + print("Consider reducing the amount of data or increasing the page size.") + + +if __name__ == "__main__": + parser = argparse.ArgumentParser(description="Generate surveillance report PDF") + parser.add_argument("--tsv", required=True, help="Input TSV file") + parser.add_argument("--functions_table", required=True, help="Functions table file") + parser.add_argument("--metadata", help="Metadata file") + parser.add_argument("--virusseq", action="store_true", help="Include VirusSeq acknowledgment") + parser.add_argument("--output", required=True, help="Output PDF file name") + args = parser.parse_args() + + # Generate PDF + generate_pdf(args.tsv, args.output, args.metadata, args.functions_table, args) \ No newline at end of file diff --git a/bin/vcf2gvf.py b/bin/vcf2gvf.py index 925290c3..2cbb81f1 100755 --- a/bin/vcf2gvf.py +++ b/bin/vcf2gvf.py @@ -21,8 +21,8 @@ from functions import parse_INFO, find_sample_size, \ get_unknown_labels, separate_attributes, rejoin_attributes, \ clade_defining_threshold, map_pos_to_gene_protein, add_alias_names, \ - add_hgvs_names -from functions import empty_attributes, gvf_columns, vcf_columns, pragmas + add_hgvs_names, empty_attributes, gvf_columns, vcf_columns, pragmas +#from functions import empty_attributes, gvf_columns, vcf_columns, pragmas def vcftogvf(vcf, strain, GENE_PROTEIN_POSITIONS_DICT, sample_size): From 0df51728fb9e4acb87e96571f0c08a6939db7e00 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 9 Dec 2024 15:19:39 -0800 Subject: [PATCH 128/161] updated conf --- conf/modules.config | 8 ++++++++ conf/nf-ncov-voc.config | 3 ++- conf/profiles.config | 4 ++++ 3 files changed, 14 insertions(+), 1 deletion(-) diff --git a/conf/modules.config b/conf/modules.config index 8c3902ef..7cad9e19 100644 --- a/conf/modules.config +++ b/conf/modules.config @@ -124,6 +124,14 @@ process { ] } + withName: TSV2PDF { + publishDir = [ + path: { "${params.outdir}/${params.prefix}/SURVEILLANCE/PDF" }, + mode: params.publish_dir_mode, + saveAs: { filename -> filename.equals('versions.yml') ? null : filename } + ] + } + // Wastewater diff --git a/conf/nf-ncov-voc.config b/conf/nf-ncov-voc.config index a86823db..95deaa9b 100644 --- a/conf/nf-ncov-voc.config +++ b/conf/nf-ncov-voc.config @@ -152,7 +152,8 @@ params { // problematic SARS-COV-2 sites probvcf = "$baseDir/assets/virus_problematicSites/NC_045512.2/problematic_sites_sarsCov2.vcf" - funcannot = "$baseDir/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.1.tsv" + funcannot = "$baseDir/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.2.tsv" + surveillance_indicators = "$baseDir/assets/virus_surveillanceIndicators/functions_df_template.tsv" skip_problematics_sites = false skip_peptide_annottaion = false genecoord = "$baseDir/assets/virus_geneCoordinates/NC_045512.2/NC_045512.2.json" diff --git a/conf/profiles.config b/conf/profiles.config index b7292ccc..40237531 100644 --- a/conf/profiles.config +++ b/conf/profiles.config @@ -64,5 +64,9 @@ profiles { executor.cpus = 16 executor.memory = 60.GB } + wave { + enabled = true + strategy = ['singularity'] + } eagle { includeConfig 'eagle.config' } } \ No newline at end of file From 0315cf9861503f236f21d5b24d158a20bf26448b Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 9 Dec 2024 15:20:05 -0800 Subject: [PATCH 129/161] updated sub-workflows --- .../virusmvp_gvf_processing_annotations.nf | 77 +++++++++---------- subworkflows/local/virusmvp_surveillance.nf | 17 ++-- 2 files changed, 50 insertions(+), 44 deletions(-) diff --git a/subworkflows/local/virusmvp_gvf_processing_annotations.nf b/subworkflows/local/virusmvp_gvf_processing_annotations.nf index 1483df29..161a4458 100644 --- a/subworkflows/local/virusmvp_gvf_processing_annotations.nf +++ b/subworkflows/local/virusmvp_gvf_processing_annotations.nf @@ -4,60 +4,59 @@ nextflow.enable.dsl = 2 // import modules -include { NCOVSPLITMUTATIONSGVF } from '../../modules/local/splitmutations_gvf' -include { NCOVSPLITMUTATIONSPOKAY } from '../../modules/local/splitmutations_pokay' -include { FUNCTIONALANNOTATION } from '../../modules/local/addFunctionalAnnotation' -include { VARIANTANNOTATION } from '../../modules/local/addVariantAnnotation' +include { NCOVSPLITMUTATIONSGVF } from '../../modules/local/splitmutations_gvf' +include { NCOVSPLITMUTATIONSPOKAY } from '../../modules/local/splitmutations_pokay' +include { FUNCTIONALANNOTATION } from '../../modules/local/addFunctionalAnnotation' +include { VARIANTANNOTATION } from '../../modules/local/addVariantAnnotation' workflow GVF_PROCESSING_ANNOTATION { take: - annotation_gvf - + annotation_gvf + main: - - if(!params.mpox){ - functional_annotation = file(params.funcannot, checkIfExists: true) - func = [ [ id:"pokay" ], functional_annotation ] - - split_names = file(params.mutationsplit, checkIfExists: true) - //split_tsv = [ [ id:params.virus_accession_id ], split_names ] - - if(!params.skip_splitting_mutations){ - - NCOVSPLITMUTATIONSPOKAY( - func, - split_names - ) - - NCOVSPLITMUTATIONSGVF( - annotation_gvf, - split_names - ) - annotation_gvf=NCOVSPLITMUTATIONSGVF.out.gvf - } - - FUNCTIONALANNOTATION( + + if (!params.mpox) { + functional_annotation = file(params.funcannot, checkIfExists: true) + func = [[id: "pokay"], functional_annotation] + + split_names = file(params.mutationsplit, checkIfExists: true) + //split_tsv = [ [ id:params.virus_accession_id ], split_names ] + + if (!params.skip_splitting_mutations) { + + NCOVSPLITMUTATIONSPOKAY( + func, + split_names + ) + + NCOVSPLITMUTATIONSGVF( annotation_gvf, - NCOVSPLITMUTATIONSPOKAY.out.tsv + split_names ) - annotation_gvf=FUNCTIONALANNOTATION.out.gvf - + annotation_gvf = NCOVSPLITMUTATIONSGVF.out.gvf } - + } + if (!params.skip_functionalannotation) { + FUNCTIONALANNOTATION( + annotation_gvf, + NCOVSPLITMUTATIONSPOKAY.out.tsv + ) + annotation_gvf = FUNCTIONALANNOTATION.out.gvf + } + + if (!params.skip_variantannotation) { variant_annotation = file(params.variant, checkIfExists: true) - variant_tsv = [ [ id:params.virus_accession_id ], variant_annotation ] - + variant_tsv = [[id: params.virus_accession_id], variant_annotation] VARIANTANNOTATION( annotation_gvf, variant_tsv, true ) - annotation_gvf=VARIANTANNOTATION.out.gvf - + annotation_gvf = VARIANTANNOTATION.out.gvf + } emit: - annotation_gvf - + annotation_gvf } diff --git a/subworkflows/local/virusmvp_surveillance.nf b/subworkflows/local/virusmvp_surveillance.nf index 15ed2869..70d17683 100644 --- a/subworkflows/local/virusmvp_surveillance.nf +++ b/subworkflows/local/virusmvp_surveillance.nf @@ -1,18 +1,25 @@ #!/usr/bin/env nextflow - nextflow.enable.dsl = 2 // import modules - include { GVF2TSV } from '../../modules/local/gvf2tsv' -//include { surveillancePDF } from '../../modules/local/archive/custom' +include { TSV2PDF } from '../../modules/local/tsv2pdf' workflow SURVEILLANCE { take: ch_gvf + ch_metadata // This will be a value channel, potentially containing null main: GVF2TSV(ch_gvf) - //surveillancePDF(surveillanceRawTsv.out.surveillancetsv.flatten(), ch_surveillanceIndicators, ch_metadata) - //ch_surv = surveillancePDF.out.surveillance_pdf + tsv = GVF2TSV.out.surveillancetsv + surveillance_indicators = Channel.value([id: "surveillance", file: params.surveillance_indicators]) + if (params.mode == 'reference') { + metadata = ch_metadata + } + else { + metadata = [[], []] + } + // Use a conditional operator to handle the case where metadata might be null + TSV2PDF(tsv, surveillance_indicators, metadata) } From 2828b74b70dee33cb39efa6b40087b74e161d014 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 9 Dec 2024 15:20:28 -0800 Subject: [PATCH 130/161] updated sars-cov-2 workflow --- workflows/covidmvp.nf | 14 ++++++++------ 1 file changed, 8 insertions(+), 6 deletions(-) diff --git a/workflows/covidmvp.nf b/workflows/covidmvp.nf index 4b313014..1e9a3cf1 100644 --- a/workflows/covidmvp.nf +++ b/workflows/covidmvp.nf @@ -59,17 +59,17 @@ workflow COVIDMVP { PREPROCESSING(metadata, sequences) metadata = PREPROCESSING.out.metadata - sequences = PREPROCESSING.out.sequences + processed_sequences = PREPROCESSING.out.sequences // Step 2: Process SEQKIT_GREP output - ch_collected_sequences = sequences + ch_collected_sequences = processed_sequences .map { it[1] } .collect() .map { seqs -> [[id: "seqkit_stat"], seqs] } if (!params.skip_qc) { - QUALITYCONTROL(sequences, ch_collected_sequences) + QUALITYCONTROL(processed_sequences, ch_collected_sequences) sequences_grouped = QUALITYCONTROL.out.sequences ch_stats = QUALITYCONTROL.out.stats } @@ -82,7 +82,7 @@ workflow COVIDMVP { } else { if (!params.skip_qc) { - QUALITYCONTROL(sequences, ch_collected_sequences) + QUALITYCONTROL(sequences, sequences) sequences_grouped = QUALITYCONTROL.out.sequences ch_stats = QUALITYCONTROL.out.stats } @@ -102,6 +102,8 @@ workflow COVIDMVP { if (!params.skip_postprocessing) { POSTPROCESSING(annotated_gvf, PREPROCESSING.out.logfile) } - - SURVEILLANCE(annotated_gvf) + if (!params.skip_surveillance) { + ch_metadata = params.metadata ? Channel.value(file(params.metadata)) : Channel.value(null) + SURVEILLANCE(annotated_gvf, ch_metadata) + } } From 5e9179a6bf0b465a9f91803fab8cb2d0e4237052 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 9 Dec 2024 15:21:05 -0800 Subject: [PATCH 131/161] updated preset param files --- covidmvp_clinical_params.yaml | 6 ++++-- covidmvp_user.yaml | 5 +++-- 2 files changed, 7 insertions(+), 4 deletions(-) diff --git a/covidmvp_clinical_params.yaml b/covidmvp_clinical_params.yaml index a0e22714..f5b8be81 100644 --- a/covidmvp_clinical_params.yaml +++ b/covidmvp_clinical_params.yaml @@ -1,6 +1,8 @@ mode: "reference" +seq: "/scratch/group_share/nextflow_workdir/mzanwar/93/c3c398c03ff4a68a688446f139cda0/2024-11-15T02%3A00%3A02Z.5f384c10-e08e-4567-ae6e-a1e26035e4b3.multi.fa.xz" +meta: "/scratch/group_share/nextflow_workdir/mzanwar/2d/63961dce3ce007283f6f9f71413044/viralai_metadata_processed.csv.gz" grouping_criteria: "lineage" -viralai: true +viralai: false virusseq: true virusseq_update: false skip_classification: true @@ -8,7 +10,7 @@ skip_postprocessing: false skip_posting: true skip_harmonize: false start_date: "2020-01-01" -end_date: "2024-10-25" +end_date: "2024-12-02" metadata_source: "ViralAi_EpiCoV" metadata_config: "/project/def-virusmvp/mzanwar/nf-ncov-voc/assets/metadata_conf/metadata.yaml" outdir: "/project/def-virusmvp/mzanwar/nf-ncov-voc/results/covidmvp" diff --git a/covidmvp_user.yaml b/covidmvp_user.yaml index 2be96f96..26f16958 100644 --- a/covidmvp_user.yaml +++ b/covidmvp_user.yaml @@ -1,12 +1,13 @@ prefix: "covidmvp-user" mode: "user" viral_aligner: "minimap2" +viralai: false skip_classification: true skip_postprocessing: true skip_posting: true skip_harmonize: true start_date: "2020-01-01" -end_date: "2024-04-15" +end_date: "2024-12-01" outdir: "results/covidmvp" -seq: "data/viralai_test.fasta.gz" +seq: "/project/def-virusmvp/mzanwar/nf-ncov-voc/data/sars-cov-2/sars-cov-2_test_data_1x.fa" # seq: "data/viralai_test.vcf" From aa97bfe4a6d8d141e2d76f6d4163dc4932404396 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 9 Dec 2024 15:22:00 -0800 Subject: [PATCH 132/161] updated tsv2pdf module --- modules/local/tsv2pdf.nf | 33 +++++++++++++++++++++++++++++++++ 1 file changed, 33 insertions(+) create mode 100644 modules/local/tsv2pdf.nf diff --git a/modules/local/tsv2pdf.nf b/modules/local/tsv2pdf.nf new file mode 100644 index 00000000..91ed6f4f --- /dev/null +++ b/modules/local/tsv2pdf.nf @@ -0,0 +1,33 @@ +process TSV2PDF { + tag "${meta.id}" + conda "conda-forge::pandas=1.4.3" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'community.wave.seqera.io/library/pip_pandas_reportlab:14a90fc25f86e9ba' + : 'community.wave.seqera.io/library/pip_pandas_reportlab:14a90fc25f86e9ba'}" + + input: + tuple val(meta), path(tsv) + tuple val(meta2), path(surveillanceindicators) + tuple val(meta3), path(metadata) + + output: + tuple val(meta), path("*.pdf"), emit: surveillance_pdf + + script: + def metadata_arg = metadata ? "--metadata ${metadata}" : "" + def virusseq_arg = params.mode == 'reference' ? "--virusseq" : "" + def prefix = task.ext.prefix ?: "${meta.id}" + + """ + echo "Inputs:" + echo "TSV file: ${tsv}" + echo "Indicators file: ${surveillanceindicators}" + echo "Metadata: ${metadata}" + surveillance_report_pdf.py \ + --tsv ${tsv} \ + --functions_table ${surveillanceindicators} \ + ${metadata_arg} \ + ${virusseq_arg} \ + --output ${prefix}.pdf + """ +} From 718781725c05cee240c71c79271a9f791af357cb Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 9 Dec 2024 15:22:23 -0800 Subject: [PATCH 133/161] version bump for pokay sars-cov-2 --- ...kay_functionalAnnotation_SARSCoV2_v4.2.tsv | 1429 +++++++++++++++++ 1 file changed, 1429 insertions(+) create mode 100644 assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.2.tsv diff --git a/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.2.tsv b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.2.tsv new file mode 100644 index 00000000..3147d7d1 --- /dev/null +++ b/assets/virus_functionalAnnotation/NC_045512.2/Pokay_functionalAnnotation_SARSCoV2_v4.2.tsv @@ -0,0 +1,1429 @@ +organism reference accession reference database name nucleotide position original mutation description nucleotide mutation amino acid mutation amino acid mutation alias gene name gene symbol protein name protein symbol measured variant functional effect inferred variant functional effect viral life cycle functional effect variant functional effect description CVX code DrugBank Accession Number Antibody Registry ID author publication year URL DOI PMID peer review status curator mutation functional annotation resource +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2(GU280_gp01):g.1438T>C YP_009724389.1:p.Phe480Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has an inhibition rate of virus production by Remdesivir of 0.80. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2(GU280_gp01):g.1438T>C YP_009724389.1:p.Phe480Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has an inhibition rate of virus production by Remdesivir of 0.78. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2(GU280_gp01):g.1438T>C YP_009724389.1:p.Phe480Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) viral load This mutant causes a 0.48x fold change in the infectious virus production rate. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2(GU280_gp01):g.1438T>C YP_009724389.1:p.Phe480Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has a 0.27x fold change in EC50 value with Remdesivir. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2(GU280_gp01):g.1438T>C YP_009724389.1:p.Phe480Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) pharmaceutical effectiveness This mutant has a 0.66x fold change in EC50 value with Remdesivir. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 1703 F480L NC_045512.2(GU280_gp01):g.1438T>C YP_009724389.1:p.Phe480Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) viral load This mutant causes a 0.41x fold change in the infectious virus production rate. Torii 2022 https://doi.org/10.1101/2022.02.22.481436 doi:10.1101/2022.02.22.481436 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 pmid:33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.526 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,22992,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,S477N,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed no significant change in IC50 serum dilution concentration for 6 convalescent sera. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 pmid:33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed 3.6x reduction in both IC50 serum dilution concentration for sera from 5 BNT162b2 (Pzifer) or 3 mRNA1273 (Moderna) vacinees collected 28 days following booster dose. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 pmid:33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.526+E484K at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 88%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 pmid:34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,21846,22317,22319,22320,23011,23012,23399,23401,23401,23402,23403,23403,23664 L5F,T95I,D253G,D253G,D253G,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed 3.8x reduction in IC50 serum dilution concentration for 6 convalescent sera. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 pmid:33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,22992,23011,23012,23664 L5F,S477N,E484K,E484K,A701V YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 114 test-positive were Iota. Two dose vaccine efficacy against Iota was 95.7 (81.7-99.0%), one dose VE was 88.8 (0.7-98.7)%. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21575,25186 L5F,Q1208H NC_045512.2(GU280_gp02):g.13C>T,NC_045512.2(GU280_gp02):g.3624G>T YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Gln1208His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Four of the convalescent sera tested showed 4-fold or greater improvement in neutralization efficiency. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21587 P9S NC_045512.2(GU280_gp02):g.25C>T YP_009724390.1:p.Pro9Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2M28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21588,21848,22132,22191,22600,22600,22907,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24138,24368 P9L,E96Q,R190S,I210T,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T859N,D936H YP_009724390.1:p.Pro9Leu,YP_009724390.1:p.Glu96Gln,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Ile210Thr,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr859Asn,YP_009724390.1:p.Asp936His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1.640.2 variant was ~5.6x folds more significant in 9 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 pmid:35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21588,21848,22132,22191,22600,22600,22907,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24138,24368 P9L,E96Q,R190S,I210T,R346S,R346S,Y449N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T859N,D936H YP_009724390.1:p.Pro9Leu,YP_009724390.1:p.Glu96Gln,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Ile210Thr,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Tyr449Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr859Asn,YP_009724390.1:p.Asp936His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in B.1.640.2 variant was ~1000x folds more significant in 8 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 pmid:35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.2 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.2 has an IC50 fold change of 0.07x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Omicron BA.2 has an IC50 fold change of 0.09x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Omicron BA.2 has an IC50 fold change of 0.08x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.2 has an IC50 fold change of 0.04x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.2 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21594,21603,21603,21614,21617,21617,21618,21618,21629,21630,21632,21633,21633,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22194,22197,22198,22198,22199,22200,22576,22577,22578,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,L24_A27delinsS,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,V213G,V213G,V213G,V213G,V213G,V213G,G339D,G339D,G339D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Leu24_Ala27delinsSer,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Omicron BA.2 variant is 0.8x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21597 S12F NC_045512.2(GU280_gp02):g.35C>T YP_009724390.1:p.Ser12Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects A variant in low % circulation, predicted to have a similar effect to the experimentally verified S12P, which introduces a new signal peptide, altering cleavage to occur between residues C15 and V16, thereby eliminating the C15-C136 disulfide bond – similarly to escape mutants at positions C15 and C136. This in turn decreases to varying degrees N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600 S13I NC_045512.2(GU280_gp02):g.38G>T YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The S13I mutation dampened binding of 5 mAbs and abrogated binding of 5 additional mAbs out of 11 neutralizing mAbs evaluated. Predicted to shift the signal peptide cleavage site from S13-Q14 to C15-V16, which can affect NTD conformation. PG: in saying S12F does not shift the signal peptide nor affect mAb binding, this manuscript appears to contradict the text of McCallum et al.'s earlier 2021 manuscript stating that S12F *does* affected some mAb binding via putative signal peptide shift. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018 S13I,W152C NC_045512.2(GU280_gp02):g.38G>T,NC_045512.2(GU280_gp02):g.456G>T YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The B.1.427/B.1.429 S13I/W152C NTD did not bind to any NTD-directed neutralizing mAbs, which are known to target a single antigenic site (antigenic site i), whereas binding of the non-neutralizing S2L20 mAb to the NTD antigenic site iv was not affected by any mutants, confirming proper retention of folding. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using HIV pseudotype: Neutralization potency of 11 Moderna mRNA1273-elicited plasma (7-27 days post-2nd dose) was reduced ~2.8-fold compared to wildtype (D614G) S. It was reduced ~4-fold in 14 Pfizer/BioNtech BNT162b2-elicited plasma (7-27 days post-2nd dose). Using VSV pseudotype: we observed a 3-fold average reduction of Pfizer/BioNtech BNT162b2-elicited plasma neutralizing activity. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Antibody neutralization assays showed 6.7-fold resistance against 7/8 convalescent plasma. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 pmid:33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 9 plasma collected 15 to 28 days after early 2020 infections, neutralization reduced 4.9-fold for B.1.427/B.1.429 compared to wildtype (D614G). In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.427/B.1.429 pseudotyped virus, as well as WT and other VOCs. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 14 of 34 RBD-specific mAbs showed reduced neutralization to the B.1.427/B.1.429 variant pseudotype. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Lineages bearing these spike mutations comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the 'California' or 'West Coast' variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI:1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Peng 2021 https://doi.org/10.1093/cid/ciab283 doi:10.1093/cid/ciab283 pmid:33788923 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Swab samples N/NP viral RNA is approximately 2-fold higher in B.1.427/B.1.429 than in non-variant viruses. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 pmid:33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Exhibits an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. a.k.a. 20C/L452R or B.1.427/B.1.429. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 pmid:33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was minimal against B.1.249 (1.7-fold). Neutralization against 10 convalescent plasma was somewhat poorer (3.1-fold). Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.427/429 reduced 2.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 in all samples at Day 43 and Day 209 using pseudotyped lentivirus neutralization in Moderna vaccinee cohort. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 pmid:34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.429 virus has reduced neutralization activity vs wild type: 2.0x (30 sera Pfizer median 9 days post 2nd dose, 35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 2.7x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 6 of 11 (55%) vaccine recipients (Moderna or Pfizer), showed 2x reduction in neutralization to a B.1.429 lineage virus. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 pmid:33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 2.3x reduction of NT50 value B.1.427 (Epsilon) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21600,22018,22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403,24374,25135 S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G,L938F,K1191N YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu938Phe,YP_009724390.1:p.Lys1191Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for CAL.20C (B.1.429), and a slight decrease in CD8+ percentage (p=0.0201) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 pmid:33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21604,21604 Q14H,Q14H NC_045512.2(GU280_gp02):g.42G>C,NC_045512.2(GU280_gp02):g.42G>T YP_009724390.1:p.Gln14His,YP_009724390.1:p.Gln14His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21605 C15R NC_045512.2(GU280_gp02):g.43T>C YP_009724390.1:p.Cys15Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21606 C15F NC_045512.2(GU280_gp02):g.44G>T YP_009724390.1:p.Cys15Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2M28 Eliminates the C15-C136 disulfide bond. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2(GU280_gp02):g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggetsing that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2(GU280_gp02):g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates neutralization by N-terminal-domain-targeting mAbs 4-19. Impairs neutralization by N-terminal-domain-targeting mAbs 4A8 and 2-17. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2(GU280_gp02):g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite 'i', but no effect on other mAbs within that supersite McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614 L18F NC_045512.2(GU280_gp02):g.52C>T YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 pmid:34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132 L18F,T20N,P26S,D138Y,R190S NC_045512.2(GU280_gp02):g.52C>T,NC_045512.2(GU280_gp02):g.59C>A,NC_045512.2(GU280_gp02):g.76C>T,NC_045512.2(GU280_gp02):g.412G>T,NC_045512.2(GU280_gp02):g.570G>T YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The neutralization titer of NTD-binding mAb159 was 133-fold reduced on P.1 compared to Victoria (~wild type), with only 64% neutralization at 10 μg/mL. Residues 20, 18, and 138 form a cluster underlying the 245–259 loop, which inserts into a groove between the light and heavy chains of Fab 159. In addition, the N-terminal residues preceding residue 18 interact with the antibody and may be perturbed. Given that there is likely a single supersite ('i') for potent NTD-binding antibodies, the binding of many of these are likely affected. Using 20 potent (primaruly anti-RBD) antibodies, neutralization was measured by a focus reduction neutralization test (FRNT) and compared with neutralization of Victoria (~wild type) and variants B.1.1.7 and B.1.351. Compared to Victoria neutralization by the mAbs was significantly impacted by P.1, with 12/20 showing > 10-fold reduction in FRNT50 titer and a number showing complete knockout of activity. The results with P.1 showed a greater impact compared to B.1.1.7 but were, as expected, similar to those with B.1.351. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 pmid:33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure CryoEM reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the “up” position. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 pmid:33688656 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 12 Moderna vaccinee sera 15 days post second dose (43 days since first vaccination), an average 2.8x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 4.8x decrease against the full P.1 type vs WA-1 was observed, though overall with a higher ID50 reciprocal value. In 10 Pfizer vaccinee sera 7 days or more post second dose (28 days or more since first vaccination), an average 2.2x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.8x decrease against the full P.1 type vs WA-1 was observed, with similar variant ID50 reciprocal value. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 pmid:33688656 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In convalescent sera one month or more post-infection in Spring 2020, an average 6.5x decrease in reciprocal ID50 value was observed ten key point mutations in Spike in the P.1 lineage vs wildtype. A 3.4x decrease against the full P.1 type vs WA-1 was observed, with better full P.1 ID50 reciprocal value compared to the 10-mutation model. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 pmid:33688656 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Amongst RBD-targeting Emergency Use Authorized monoclonal antibody treatments CB6, LY-CoV555 and REGN10933 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1, but REGN10987 activity remains strong. RBD-targeting monoclonal antibodies 2-15 and C121 show abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. N terminal domain targeting monoclonal antibodies 5-7, 4-8, 4-18 and 2-17 have abrogated neutralization activity against the ten key point mutations in Spike in the P.1 lineage vs wildtype or WA-1. Wang 2021 https://doi.org/10.1101/2021.03.01.433466 doi:10.1101/2021.03.01.433466 pmid:33688656 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection After a 128 day interval, a patient in Sao Paulo State, Brazil reinfected with P.1 (first episode likely predates P.1 emergence). Both cases were fairly mild (difficulty breathing, tiredness, dizziness and fatigue). Malta Romano 2021 https://doi.org/10.1590/S1678-9946202163036 doi:10.1590/S1678-9946202163036 pmid:33909850 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 349 test-positive were Gamma. Two dose vaccine efficacy against Gamma was 95.5 (90.9-97.8%), one dose VE was 74.2 (43.8-88.1%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~6x cleavage of S2 relative to WA1 (D614G) wildtype by Gamma variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but H655Y is upstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Three healthcare workers (29-50yo) had confirmed P.1 [Gamma] re-infection in the Amazonas region of Brazil 3-9 months after initial infection from viruses with distinct lineage from P.1, but mild symptoms upon re-infection and evidence for infectiousness during re-infection. Naveca 2021 https://doi.org/10.21203/rs.3.rs-318392/v1 doi:10.21203/rs.3.rs-318392/v1 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 3.0x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 4.1x reduction of NT50 value P.1 (Gamma) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Gamma (P.1) variant is 0.6x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was slightly lower against B.1.1.248 variant constellation in sera tested from most of the 15 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 16.6% in this B.1.1.248 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 pmid:33972942 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.248 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07. B.1.1.248 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.7 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0039 for mild resistance. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Unlike wild type or B.1.1.7, P.1 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. Montagutelli 2021 https://doi.org/10.1101/2021.03.18.436013 doi:10.1101/2021.03.18.436013 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.248 variant constellation in 10 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples, P=0.0020. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 4.3-fold against P.1 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 pmid:33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped P.1 virus has reduced neutralization activity vs wild type: 6.7x (30 sera Pfizer median 9 days post 2nd dose) and 4.5x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using P.1 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In human sera 8 weeks post-vaccination with INO-4800, a ~2-fold reduction in P.1 neutralization was observed. Andrade 2021 https://doi.org/10.1101/2021.04.14.439719 doi:10.1101/2021.04.14.439719 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Among 46,884 HCWs in Manaus, Brazil vaccinated with at least one dose of CoronaVac, a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%; 95% CI, 11.3 - 71.4) in the odds of symptomatic SARS-CoV-2 infection was observed during the period 14 days or more after receiving the first dose. Estimated vaccine effectiveness of at least one dose against any SARS-CoV-2 infection was 35.1% (95% CI, −6.6 - 60.5) in the same time period. Hitchlings 2021 https://doi.org/10.1101/2021.04.07.21255081 doi:10.1101/2021.04.07.21255081 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness VSV pseudotype P.1 entry mediated by the S proteins of the P.1 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Cell fusion proficiency was slight impaired. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding VSV pseudotype P.1 showed 4.8-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections). Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype P.1 showed 5.12-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking VSV pseudotype P.1 showed slight decrease in cell entry relative to wild type in 262T and 263T-ACE2 (kidney) cell lines. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Neutralizing antibodies that were generated following a mild infection with SARS-CoV-2 B.1.128 were effective in vitro, and likely protective, against the SARS-CoV-2 P.1. variant in the majority of individuals based on 60 convalescent sera tested. Mendes-Correa 2021 https://doi.org/10.1101/2021.05.11.21256908 doi:10.1101/2021.05.11.21256908 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ or CD8+ cell count effect for P.1 by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 pmid:33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for P.1 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the P.1 variants used, using the most popular as a stand in] McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.15x *increase* in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against P.1 reduced 3.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness P.1 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with Lilly mAb combination LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of P.1. There was also escape from neutralization of P.1 by REGN10933 (one of 2 in Regeneron's mAb cocktail) and a modest reduction in neutralization of P.1 by AstraZeneca's AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized P.1 with all reaching a plateau at 100% neutralization; interestingly, ADG30 showed a slight increase of neutralization of P.1. S309 Vir was largely unaffected, although for several viruses, including P.1, the antibody failed to completely neutralize, conceivably reflecting incomplete glycosylation at N343, since the sugar interaction is key to binding of this antibody. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 pmid:33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy P.1 lineage titers were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer (sera collected 4-14 days post-booster) and ChAdOx1 nCoV-19 AstraZeneca (sera collected 14 or 28 days post-booster) vaccines respectively. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 pmid:33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 2896 for P.1 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 pmid:33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 256 for B.1.1.7 virus. Compare to somewhat stronger neutralization titer for wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 pmid:33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against P.1 at various time points using pseudovirus neutralization in Moderna vaccinee cohort: Day 43 100%, Day 209 85%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 pmid:34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,22812,22812,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,24642,25088 L18F,T20N,P26S,D138Y,R190S,K417T,K417T,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I,V1176F YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion PBMCs of 11 mild COVID-19 patients collected 38-80 days after symptom onset were stimulated with the 15-mer peptide pools (w/ 10 residue overlaps) from the wholle viral proteome, showing no significant CD4+ cell count effect for P.1, and a slight increase in CD8+ percentage (p=0.0195) by Activation Induced Marker (AIM) assay (cellular immunity measurement). [in the text, this increase is not noted as signficant, even though p=0.05 is used elsewhere in the text as a signficance threshold] Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 pmid:33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21621,21638,21974,22132,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525 L18F,T20N,P26S,D138Y,R190S,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The relative transmissibility of P.1 estimated at the national level (Italy) varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. PG: variant list has been abbreviated due to mixed K417 bases in this lineage, potential miscalls of deletions Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21801,22206,22334,22600,22600,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22986,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D80A,D215G,W258R,R346S,R346S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,A475V,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ala475Val,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments and mutations from variants of concern completely ablates neutralization in 19 of 21 convalescents plasma collected mean 1.3 months post infection. [actual Y145del from manuscript substituted with more common Y144del description] Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801 L18F,D80A NC_045512.2(GU280_gp02):g.52C>T,NC_045512.2(GU280_gp02):g.239A>C YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The L18F and D80A of the B.1.351 lineage lead to reconfiguration of the N-terminal segment despite the disulfide between Cys16 and Cys136 that partly anchors the N-terminal peptide. The most consequential changes are probably from the triple residue deletion... which causes a shift of the nearby loop 144-155 and must also reconfigure the adjacent disorder loop (residues 246-260), both of which form part of the neutralizing epitopes...bringing large changes in the antigenic surface in this region. Cai 2021 https://doi.org/10.1101/2021.04.13.439709 doi:10.1101/2021.04.13.439709 pmid:33880477 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The 501Y.V2 to first wave IC50 ratio ranged from 6 to 200-fold. Averaging across all 7 participant convalescent sera highlighted the dramatic decrease in sensitivity to neutralization of authentic 501Y.V2 variants. PG: I'm purposefully ignoring D614G and A701V as contributors Cele 2021 https://doi.org/10.1038/s41586-021-03471-w doi:10.1038/s41586-021-03471-w pmid:33780970 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In human sera 8 weeks post-vaccination with INO-4800, a ~7-fold reduction in B.1.351 neutralization was observed. Andrade 2021 https://doi.org/10.1101/2021.04.14.439719 doi:10.1101/2021.04.14.439719 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Four fold reduction in neutralization efficiency was observed in sera of ferrets post-vaccination with INO-4800 (DNA plasmid pGX9501 encoding full length Spike). Riddell 2021 https://doi.org/10.1101/2021.04.17.440246 doi:10.1101/2021.04.17.440246 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. In a mouse study, primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Wu 2021 https://doi.org/10.1101/2021.04.13.439482 doi:10.1101/2021.04.13.439482 pmid:33880468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pzifer vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1), but were all infected before 14 days post second vaccination. Kustin 2021 https://doi.org/10.1101/2021.04.06.21254882 doi:10.1101/2021.04.06.21254882 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 8.2x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 6.3x reduction of NT50 value B.1.351 (Beta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals (5/9) and recipients of a only a single dose of mRNA vaccine (10/11) – heterotypic neutralization dropped to negligible levels, particularly against B.1.351. Skelly 2021 https://doi.org/10.21203/rs.3.rs-226857/v1 doi:10.21203/rs.3.rs-226857/v1 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 8 for B.1.351 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 pmid:33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.351 sample. Contrast this with 1.4-fold reduction for just the pseudovirus combination of 'key' B.1.351 mutations K417N+E484K+N501Y. WA1 and B.1.351 FRNT50 titers correlated weakly at the individual level, with some individual’s serum potently neutralizing WA1 while having FRNT50 for B.1.351 below the assay limit of detection (1:20). Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 pmid:33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Sera from individuals who have been infected with Delta does not have strong neutralising activity against Beta. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms had mean ~6x reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against Beta. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Beta Variant B.1.351 RBD significantly better than w.t. SARS-CoV-2 RBD. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.351 v2 virus has reduced neutralization activity vs wild type: 41.2x (30 sera Pfizer median 9 days post 2nd dose) and 20.8x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Pseudotype lentivirus for the full B.1.351 Spike variant list shows increase affinity for ACE2 as measured by IC50. This is in contrast to B.1.1.7 which showed no major change, indicating that the shared N501Y mutation is the driver of affinity change, attentuated in the B.1.1.7 mutatioon set, but maintained in the B.1.351 lineage. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy [Contrary to how this paper has been cited, Voysey et al. do NOT show evidence of decreased effectiveness of ChAdOx1 (AstraZeneca) against the South African B.1.351 lineage. Insufficient numbers reaching the primary study endpoint were available in that arm of the vaccine study to report any statistics from the South African participants. Additionally, the study period of the paper ended in November 2020, while the earliest reported case of this lineage is October (covariants.org), only becoming dominant by mid-November.] Voysey 2021 https://doi.org/10.1016/S0140-6736(20 doi:10.1016/S0140-6736(20 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.351. We observed an increase (relative to D614G) in binding of soluble ACE2 to B.1.351, and to a much gearter extent to B.1.1.7, which both carry the N501Y mutation (see Fig 3). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed for B.1.351 a CD4+ cell count decrease (29%, p=0.00063) as well as CD8+ (33%, p=0.0016) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 pmid:33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1.1.117, PRNT50 line virus neutralizating antibody activity assay of B.1.351 showed ~11x reduction in 13 vacinees's sera collected through 41 days after vaccination. Neutralization by a placebo control group of 6 naturally infected patients showed a smaller ~8x drop (starting from a ~50% higher PRNT50 value than vacinees for B.1.1.117 neutralization). Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed ~4x reduction in neutralization (ID50) for full B.1.351 pseudotype HIV-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a slightly higher 4.6x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera). Madhi 2021 https://doi.org/10.1056/NEJMoa2102214 doi:10.1056/NEJMoa2102214 pmid:33725432 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Beta neutralizing antibodies is 0.899x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape A 1.8-fold drop in FRNT50 for B.1.351 was observed in 44 sera collected between 1 and 301 post-infection. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 pmid:33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 3.2x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v1 reduced 6.9x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Encouragingly, we find that the majority of T cell responses in recipients of two doses of the BNT162b2 vaccine are generated by epitopes that are invariant between the [wildtype] and two of the current variants of concern (B.1.1.7 and B.1.351). In over 90% of two dose mRNA vaccinees, heterotypic neutralizing titres (NT50) against B.1.1.7 and B.1.351 remain comfortably above the level associated with immune protection in recent vaccine trials. However, in over 50% of convalescent COVID-19 individuals and recipients of a only a single dose of mRNA vaccine – heterotypic neutralization dropped to negligible levels, particularly against B.1.351. Skelly 2021 https://doi.org/10.21203/rs.3.rs-226857/v1 doi:10.21203/rs.3.rs-226857/v1 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The neutralizing activity of 16/20 convalescent sera was significantly lower against this pseudotyped virus model of B.1.351, with similar results for the live virus. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Beta neutralizing antibodies is 0.803x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.351 pseudotyped virus model ablates neutralization by RBD-directed mAbs CB6, 4-20, 2-4, 2-43, 910-30, 2-302-15, LY-Cov555, C121. B.1.351 pseudotyped virus model severely impairs neutralization by RBD-directed mAb 1-20. B.1.351 pseudotyped virus model impairs neutralization by RBD-directed mAb REGN10933. B.1.351 pseudotyped virus model ablates neutralization by N-terminal-domain-directed mAbs 5-24, 4-8, 4A8, 4-19. B.1.351 pseudotyped virus model severely impairs neutralization by N-terminal-domain-directed mAb 2-17. B.1.351 pseudotyped virus model impairs neutralization by N-terminal-domain-directed mAb 5-7. PG: Live virus data for the same mAbs is similar, but 1-20 becomes severally impaired, REGN10933 activity is ablated, and Brii-196 becomes impaired. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 (12.4x in twelve Moderna-recipient sera; 10.3x in ten Pfizer-recipient sera). [this is a larger list of B.1.351 than modeled by Wang et al. (2021) by including L18F and R246I, less effective at neutralizing] Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The sera of 16 individuals with time course collection was evaluated against VSV pseudotypes: while BD614G and B.1.1.7 were neutralized earlier, the anti-B.1.351 response was negative up to week 3, and became detectable at week 4 (1 week after booster dose), at a level lower than the two other viruses (~10x vs D614G) through week 6, the last timepoint measured. Three vaccinees never showed detectable neutralization to B.1.351 even after second dose. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR16m molecule had a 0.036x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: while B.1.1.7 and D614G showed neutralization by nasal swab from only one different previously infected vacinee neutralizing at weeks 3 and 6, B.1.351 showed zero neutralization at either time point in any sample (and relatively impaired serum neutralization). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v2 reduced 7.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.351 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 pmid:33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. Only 1 out of 12 serum samples from a cohort of Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) at full serum strength (average realtive decrease was 6.1x vs wild type). Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 pmid:33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.07x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a randomized phase 2a-b control trial of the Novavax (NVX-CoV2373) vaccine in South Africa, where B.1.351 virus dominates, efficacy was 60.1% (95% CI, 19.9 to 80.1) in HIV-negative and initially SARS-CoV-2 seronegative participants using the primary endpoint of laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants. Shinde 2021 https://doi.org/10.1056/NEJMoa2103055 doi:10.1056/NEJMoa2103055 pmid:33951374 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR22 molecule had a 1.57x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.054x fold change in IC50 in B.1.351 Beta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness B.1.351 virus neutralization (as tested using biolayer interferometry) of both Lilly antibodies was severely impacted, with LY-CoV16 and LY-CoV555 (due to mutations at 416 and 484 respectively) shows almost complete loss of neutralization of B.1.351. There was also escape from neutralization of B.1.351 by REGN10933 and a modest reduction in neutralization of B.1.351 by AZD8895 (while AZD1061 and AZD7442 showed equal neutralization of all SARS-CoV-2 variants tested). The three Adagio antibodies neutralized B.1.351. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 pmid:33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR16m molecule had a 6.7x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness DARPin SR16m molecule had a 99.7x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 L18F,D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with all key mutations from B.1.351 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting some synergy between the mutations to decrease cell entry fitness (i.e. cell entry is liklely not the driver of this lineage's dominance). Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22206,23060,23061,23062,23062,23063,23063,22810,22810,22811,22812,22813,22813,22813,23011,23012,23399,23401,23401,23402,23403,23403 L18F,D80A,D215G,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The most significant loss of neutralizing activity (PsVNA50 assay) using 6 hyperimmune immunoglobulin preparations from convalescent plasma was seen against authentic B.1.351 lineage virus (9.2-fold). Neutralization against 10 convalescent plasma was poorer (18.7x). Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks. Meister 2021 https://doi.org/10.1093/infdis/jiab260 doi:10.1093/infdis/jiab260 pmid:33993274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 L18F,D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation set (B.1.351+) demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525 L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the Parana state of Brazil, patients aged 20-29 years experienced a tripling of their case fatality rate (CFR), from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling comparing February to January in 2021. Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil. [this is somewhat indirect evidence that assume greatly increasing proportion of P.1 cases in March (70%) compared to February, but the first official ID of P.1 in Parana state (Feb 16th) may be due to testing procedures rather than actual prevalence] Santos de Oliviera 2021 https://doi.org/10.1101/2021.03.24.21254046 doi:10.1101/2021.03.24.21254046 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525 L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the Southern Brazilian stats of Rio Grande do Sul, comparing pre-P.1 and post-P.1 waves: The increase in Case Fatality Rate occurred in a greatest intensity in the population between 20 and 59 years old and among patients without pre-existing risk conditions. Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95%CI = 2.9 - 11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95%CI = 5.01-11.83; p <0.0001) comparing with November-December. This maybe due to a combination of changes in pathogenicity and virulence profiles, and health system overload. [exact mutations used to define P.1 lineage not disclosed in this publication] Ribas Freitas 2021 https://doi.org/10.1101/2021.04.13.21255281 doi:10.1101/2021.04.13.21255281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525 L18F,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using P.1 defining mutations: Significant shift to infection in those without pre-existing conditions (27.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (20% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.1% vs 0.6% for non-VOC cases). Significant increase in health care worker rate (19.8% vs 8.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 pmid:33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21614,22915,22915,22916,22916,22917,22917,23060,23061,23062,23062,23063,23063,23520,23521,23521,23522,23524,23524,23525,23525,23944,23944,23946,23947,23948,23948,25218 L18F,L452R,L452R,L452R,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A653V,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,G1219V YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala653Val,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gly1219Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 (Pfizer) vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains. Mallm 2021 https://doi.org/10.1101/2021.04.27.21254849 doi:10.1101/2021.04.27.21254849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21622,21624,22022,22216,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24863 R21T,R21T,E154K,Q218H,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,H1101D YP_009724390.1:p.Arg21Thr,YP_009724390.1:p.Arg21Thr,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Gln218His,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.His1101Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In two of eight cell lines tested (Caco-2 intenstinal and Calu-3 lung), a modest increase in cell entry was observed. This increase was not observed in a Calu-3 cell line with overexpressed ACE2. [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21622,21624,22022,22216,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24863 R21T,R21T,E154K,Q218H,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,H1101D YP_009724390.1:p.Arg21Thr,YP_009724390.1:p.Arg21Thr,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Gln218His,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.His1101Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Approximately 2-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21622,21624,22022,22216,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24863 R21T,R21T,E154K,Q218H,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,H1101D YP_009724390.1:p.Arg21Thr,YP_009724390.1:p.Arg21Thr,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Gln218His,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.His1101Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abrogates Bamlanivimab neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Significant decrease in combined Etesevimab+Bamlanivimab neutralization except at the highest concentration measured. [PG: note that the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21622,21624,22022,22216,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24863 R21T,R21T,E154K,Q218H,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,H1101D YP_009724390.1:p.Arg21Thr,YP_009724390.1:p.Arg21Thr,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Gln218His,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.His1101Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 15 Pfizer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~3x (compared to ~11x for B.1.351). [the virus tested as B.1.617 overlaps only partially with the Spike mutation lists used by PANGO, CDC, etc. for this lineage therefore the results should be interpreted carefully as transferable to B.1.617 generally] Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21627 T22I NC_045512.2(GU280_gp02):g.65C>T YP_009724390.1:p.Thr22Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain, frequently observed in various human infection lineages, reduces the tropism of SARS-CoV-2 in F81 (cat kidney, Felis catus) and BHK-21 (golden hamster kidney, Mesocricetus auratus) cell line cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21641,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23946,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22783,22783,22784,22785,22786,22786,22671,22672,22672,22673,22674,22679,22679,22686,22992,21594,21603,21603,21614,21617,21617,21618,21618,22992,22995,22194,22197,22198,22198,22199,22200,23071,23071,23074,23074,23075,23075 A27S,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,R408S,R408S,R408S,R408S,R408S,R408S,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T478K,T478K,V213G,V213G,V213G,V213G,V213G,V213G,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 3.9x-fold lower (95% CI: 0.14x-0.17x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21641,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23946,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22783,22783,22784,22785,22786,22786,22671,22672,22672,22673,22674,22679,22679,22686,22992,21594,21603,21603,21614,21617,21617,21618,21618,22992,22995,22194,22197,22198,22198,22199,22200,23071,23071,23074,23074,23075,23075 A27S,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,R408S,R408S,R408S,R408S,R408S,R408S,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T478K,T478K,V213G,V213G,V213G,V213G,V213G,V213G,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 78fM for binding to the Omicron BA.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21641,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23946,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22783,22783,22784,22785,22786,22786,22671,22672,22672,22673,22674,22679,22679,22686,22992,21594,21603,21603,21614,21617,21617,21618,21618,22992,22995,22194,22197,22198,22198,22199,22200,23071,23071,23074,23074,23075,23075 A27S,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,R408S,R408S,R408S,R408S,R408S,R408S,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T478K,T478K,V213G,V213G,V213G,V213G,V213G,V213G,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2 (from South Africa/CERI-KRISP-K032307/2021) were 4.5-fold lower (95% CI: 4.3x-4.7x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21641,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23946,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22917,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22783,22783,22784,22785,22786,22786,22671,22672,22672,22673,22674,22679,22679,22686,22992,23673,21594,21603,21603,21614,21617,21617,21618,21618,22992,22995,22194,22197,22198,22198,22199,22200,23071,23071,23074,23074,23075,23075 A27S,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,R408S,R408S,R408S,R408S,R408S,R408S,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,S704L,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T478K,T478K,V213G,V213G,V213G,V213G,V213G,V213G,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Ser704Leu,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 4.2-fold lower (95% CI: 5.8x-6.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21641,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23946,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22917,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22783,22783,22784,22785,22786,22786,22671,22672,22672,22673,22674,22679,22679,22686,22992,23673,21594,21603,21603,21614,21617,21617,21618,21618,22992,22995,22194,22197,22198,22198,22199,22200,23071,23071,23074,23074,23075,23075 A27S,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,L452Q,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,R408S,R408S,R408S,R408S,R408S,R408S,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,S704L,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T478K,T478K,V213G,V213G,V213G,V213G,V213G,V213G,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Ser704Leu,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.2.12.1 (from USA/NY-CDC-ASC210722700/2022) were 3.9x-fold lower (95% CI: 0.14x-0.18x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21648 T29I NC_045512.2(GU280_gp02):g.86C>T YP_009724390.1:p.Thr29Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21717,21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23011,23012,23399,23401,23401,23402,23403,23403,23593,23593,24224 Q52R,A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H,F888L YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.525 reduced 4.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21717,23011,23012,23593,23593,24224 Q52R,E484K,E484K,Q677H,Q677H,F888L YP_009724390.1:p.Gln52Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Phe888Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The B.1.525 appears to have poor transmissibility when in competition with B.1.1.7 and other circulating strains in Denmark (early 2021). Albertsen 2021 https://www.covid19genomics.dk/2021-05-08_data-overview.html#b1525 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21752,21752 W64R,W64R NC_045512.2(GU280_gp02):g.190T>C,NC_045512.2(GU280_gp02):g.190T>A YP_009724390.1:p.Trp64Arg,YP_009724390.1:p.Trp64Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21759 H66R NC_045512.2(GU280_gp02):g.197A>G YP_009724390.1:p.His66Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent, especially on a D614 wildtype background. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21987,21990,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23039,23040,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron (a.k.a. B.1.1.529) Spike pseudotyped VSV and Vero E6 cells has somewhat reduced neutralization (2.7x) vs wild type with monoclonal antibody Sotrovimab (a.k.a. VIR-7831). [delins at 214 omitted for syntax compatibility] Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21987,21990,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23039,23040,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,Y145del,Y145del,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493R,Q493R,Q493R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron breakthrough infection after 3-dose vaccination resulted in a further 3.5-fold and 2.9-fold increase of Omicron BA.1 and BA.2 neutralizing titers. Omicron BA.4/5 showed the highest neutralization resistance of all variants tested, resulting in low geometric mean neutralizing titers in plasma samples obtained after the second vaccine dose (NT50=72). Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Omicron BA.1 has an IC50 fold change of 0.08x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron B.1.1.529 (BA.1) neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron (B.1.1.529 [BA.1]) have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Omicron BA.1 has an IC50 fold change of 0.30x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigms’ ACE-2 variant LVE/STR chimera binds to SARS-2 Omicron variant B.1.1.529 spike protein trimer with high affinity. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 73 pM for binding to the Omicron B.1.1.529. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Omicron BA.1 has an IC50 fold change of 0.38x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding All 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 729 NT50. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 pmid:35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Delta variant and was used to determine neutralizing antibodytitres. There was a 24.63x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 4.21x fold increase in antibody response pre-reinfection. There was a 39.27x fold increase in antibody response during reinfection. Shete 2022 https://doi.org/10.1101/2022.05.12.491584 doi:10.1101/2022.05.12.491584 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against B.1 variant and was used to determine neutralizing antibodytitres. There was a 6.76x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 2.06x fold increase in antibody response pre-reinfection. There was a 8.18x fold increase in antibody response during reinfection. Shete 2022 https://doi.org/10.1101/2022.05.12.491584 doi:10.1101/2022.05.12.491584 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding All 10 individuals with 3 doses of the BNT162b2/BNT162b2 vaccine had a neutralizing titer in B.1 variant at an average of 3319 NT50. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 pmid:35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Plaque reduction neutralization test (PRNT) was used uring primary infection, post sixty daysof second dose vaccination, pre-reinfection and reinfection against Omicron variant and was used to determine neutralizing antibodytitres. There was a 114.84x fold increase in antibody response from first infection to recovered and vaccinated with 2 doses (60 days). There was a 6.61x fold increase in antibody response pre-reinfection. There was a 1194.9x fold increase in antibody response during reinfection. Shete 2022 https://doi.org/10.1101/2022.05.12.491584 doi:10.1101/2022.05.12.491584 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Omicron BA.1 variant is 1.0x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22673,22679,22679,22686,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22894,22896,22898,22992,22992,22995,23009,23010,23012,23013,23039,23048,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23202,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24130,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469,24503 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,S371L,S373P,S373P,S375F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,G446S,G446S,G446S,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,G496S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,N856K,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K,L981F YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Leu981Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Omicron BA.1 has an IC50 fold change of 1.26x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.3 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22992,22992,22995,23009,23010,23012,23013,23039,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075,23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525,23595,23596,23596,23598,23599,23604,23604,23853,23854,23854,23944,23944,23946,23947,23948,23948,24421,24421,24422,24423,24424,24424,24424,24465,24466,24466,24468,24469 A67V,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,S477N,T478K,T478K,E484A,E484A,E484A,E484A,Q493K,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N679K,N679K,N679K,N679K,N679K,P681H,P681H,N764K,N764K,N764K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N969K,N969K,N969K,N969K,N969K YP_009724390.1:p.Ala67Val,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.3 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23946,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22894,22896,22898,21763,21764,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22671,22672,22672,22673,22674,22679,22679,22686,22992,21846,22992,22995,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075 A67V,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G446S,G446S,G446S,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 4.2x-fold lower (95% CI: 0.15x-0.20x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,22771,22775,22775,23399,23401,23401,23402,23403,23403,23944,23944,23946,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22894,22896,22898,21763,21764,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,23854,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22671,22672,22672,22673,22674,22679,22679,22686,22992,21846,22992,22995,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075 A67V,D405N,D405N,D405N,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G446S,G446S,G446S,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,S477N,T95I,T478K,T478K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.3 (from South Africa/NICD-N22404/2021) were 6.2-fold lower (95% CI: 11.8x-14.3x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,23399,23401,23401,23402,23403,23403,23944,23944,23946,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22894,22896,22898,23048,21763,21764,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,23854,24130,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22673,22679,22679,22686,22992,21846,22992,22995,23202,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075 A67V,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G446S,G446S,G446S,G496S,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,N856K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,S371L,S373P,S373P,S375F,S477N,T95I,T478K,T478K,T547K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy paired testing of vaccine sera against ancestral virus compared to Omicron BA.1 shows that 3-dose vaccine regimen provides over 50x fold increase in protection against Omicron(B.1.1.529 [BA.1]) compared to a 2-dose regimen. Hao 2022 https://doi.org/10.1101/2022.08.12.22278720 doi:10.1101/2022.08.12.22278720 pmid:36032965 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,23399,23401,23401,23402,23403,23403,23944,23944,23946,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22894,22896,22898,23048,21763,21764,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,23854,24130,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22673,22679,22679,22686,22992,21846,22992,22995,23202,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075 A67V,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G446S,G446S,G446S,G496S,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,N856K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,S371L,S373P,S373P,S375F,S477N,T95I,T478K,T478K,T547K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness 4th antigenic exposure with Omicron (B.1.1.529 [BA.1])(n=29) infection increased variant specific plasma antibody and memory B cell responses as well as overall increased strain specific memory in individuals aged 22 –79 years, median age=33.5 years. Data collected 2.4 months after 3rd vaccination. Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,23399,23401,23401,23402,23403,23403,23944,23944,23946,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22894,22896,22898,23048,21763,21764,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,23854,24130,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22673,22679,22679,22686,22992,21846,22992,22995,23202,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075 A67V,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G446S,G446S,G446S,G496S,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,N856K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,S371L,S373P,S373P,S375F,S477N,T95I,T478K,T478K,T547K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 3.4-fold lower (95% CI: 3.2x-3.6x) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21762,23399,23401,23401,23402,23403,23403,23944,23944,23946,23947,23948,23948,23009,23010,23012,23013,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22576,22577,22578,22894,22896,22898,23048,21763,21764,23521,23521,23522,23524,23524,23525,23525,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,23060,23061,23062,23062,23063,23063,23595,23596,23596,23598,23599,23853,23854,23854,24130,24465,24466,24466,24468,24469,23604,23604,23039,23039,23040,23053,23053,23054,23054,23055,23055,24421,24421,24422,24423,24424,24424,24424,22673,22679,22679,22686,22992,21846,22992,22995,23202,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21987,21990,23071,23071,23074,23074,23075,23075 A67V,D614G,D614G,D614G,D614G,D614G,D614G,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,E484A,E484A,E484A,E484A,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G339D,G339D,G339D,G446S,G446S,G446S,G496S,H69del,H69del,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,N856K,N969K,N969K,N969K,N969K,N969K,P681H,P681H,Q493R,Q493R,Q493R,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,S371L,S373P,S373P,S375F,S477N,T95I,T478K,T478K,T547K,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Ala67Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.1 (from Botswana/R40B59_BHP_3321001248/2021) were 28.7x-fold lower (95% CI: 0.03x-0.05) than against US-WA1/2020 using an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Neutralization activity of almost all Moderna Phase 1 sera tested actually *increased*. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence The delH69/V70 enhances viral infectivity, indicating its effect on virus fitness is independent to the N501Y RBM change [with which it is found in lineage B.1.1.7] Possibly arisen as a result of the virus evolving from immune selection pressure in infected individuals and possibly only one chronic infection in the case of lineage B.1.1.7. Kemp 2020 https://doi.org/10.1101/2020.12.14.422555 doi:10.1101/2020.12.14.422555 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization activity of almost all convalescent sera tested decreased ~2x. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization activity of convalescent sera tested decreased ~2x with this B.1.1.7 pseudotyped virus. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduces neutralization by structurally unmapped mAb COVA1-21 (cluster XI). Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This deletion outside the receptor binding domain in pseudotyped VSV promoted the capacity of pseudotyped VSV to transduce black flying fox (Pteropus alecto) kidney PabKi.1 cells (17.8%) to a level twice that of human epithelial-like Huh-7 cells (9.8%) Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding No notable change in neutralization efficiency, despite N439K by itself showing a ~2x decrease on average in 16 health workers' convalescent sera. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21987,21990,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was somewhat lower against B.1.1.7 in sera tested from most of the 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21987,21990,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.7 variant constellation ablates Class 3 N-terminal domain targeting antibody COV2-2489. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,21987,21990,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y145del,Y145del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 8.8-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against cultured B.1.1.7 sample. Contrast this with 1.3-fold reduction for just the pseudovirus combination of 'key' B.1.1.7 mutation N501Y. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 pmid:33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,22920 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, much closer to D614G activity level than Y453F alone, suggesting compensatory effects between the deletion and the mutation in human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,22920 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing moderate decrease in infection rate amongst the cells, significantly lower than the deletion or Y453F alone, or their combination, suggesting a synergistic effect on poorer human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,22920,23399,23401,23401,23402,23403,23403,25249,25249,25249 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,D614G,D614G,D614G,D614G,D614G,D614G,M1229I,M1229I,M1229I YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.298 virus has reduced neutralization activity vs wild type: 1.4x (30 sera Pfizer median 9 days post 2nd dose) and 1.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,22920,24999,25000 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,S1147L,S1147L YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Ser1147Leu,YP_009724390.1:p.Ser1147Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild to modest decrease in infection rate amongst the cells, suggesting a net mild negative effect on human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,22920,25249,25249,25249 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Lentiviral pseudotyped with the key mutations from Mink Cluster 5 was neutralized more easily than D614G in 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,22920,25249,25249,25249 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells, markedly higher infectivity than either mutation alone, suggesting a synergistic net neutral effect on human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,22920,25249,25249,25249 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,Y453F,M1229I,M1229I,M1229I YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with all key mutations from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (~50%) decrease in infection rate amongst the cells, suggesting that this anthropozoonotic event is driven by other factors at the expense of human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23011,23012,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.7+E484K reduced 2.8x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Compare with 1.2x reduction for B.1.1.7 without E484K. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23011,23012,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera after the second dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 + E484K variant of ~6.7x, markedly higher than B.1.1.7 alone. For first dose sera, a 9.7x drop was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23011,23012,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization capacity GMT of 27 subjects' sera post-infection was markedly worse against B.1.1.7 + E484K than the lineage alone, with a 11.4x drop. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, moreso than this combination with the addition of P681H. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence In comparison of B.1.1.7 lineage (193 cases) vs. 'wildtype' (125) in Berlin Jan 18 to March 29 2021, significant symptom changes are absent loss of smell/taste (P=0.01), longer symptom duration (P=0.02). Mean age was 36 yo. van Loon 2021 https://doi.org/10.1101/2021.04.15.21255389 doi:10.1101/2021.04.15.21255389 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This mutation combination causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x). PG: these effects are laregly missing in the deletion-alone data Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence A higher proportion of cases infected with the B.1.1.7 variant were hypoxic on admission compared to other variants (70.0% vs 62.5%, p=0.029), in London between March 13th 2020 and February 17th 2021 (400 B.1.1.7 cases out of 1470 total sequenced). Snell 2021 https://doi.org/10.1101/2021.03.16.21253377 doi:10.1101/2021.03.16.21253377 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 pmid:33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 2.6x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.1.7 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 33%, Day 43 100%, Day 119 100%, Day 209 96%. Detectable antibodies against B.1.1.7 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 54%, Day 43 100%, Day 119 100%, Day 209 88%. Detectable antibodies against B.1.1.7 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 83%, Days 43,119,209 100%. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 pmid:34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using national surveillance data from Israel, using Pfizer vaccine and an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections: Adjusted estimates of vaccine effectiveness 7+ days after second dose were 95·3% (95% CI 94.9–95.7); 91.5% against asymptomatic SARS-CoV-2 infection (90·7–92·2; 40.9 vs 1.8 per 100 000 person-days), 97·0% against symptomatic COVID-19 (96.7–97.2%), 97.2% against COVID-19-related hospitalisation (96.8–97.5%), 97.5% against severe or critical COVID-19-related hospitalisation (97.1–97.8%), and 96.7% against COVID-19-related death (96.0–97.3%). In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined Haas 2021 https://doi.org/10.1016/S0140-6736(21 doi:10.1016/S0140-6736(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 8192 for B.1.351 virus. This compares favorably (stronger) to post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 pmid:33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure CryoEM analysis of B.1.1.7 demonstrates an increased propensity for 'up', receptor accessible conformation of the Spike protein trimer. Cai 2021 https://doi.org/10.1101/2021.04.13.439709 doi:10.1101/2021.04.13.439709 pmid:33880477 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy SARS-CoV-2 infection was confirmed in three HCWs working a single shift; all presented with mild symptoms of COVID-19. The two physicians were fully vaccinated with BNT162b2 vaccine, with the second dose administered 1 month before symptom onset. Both had high titres of IgG anti-spike antibodies at the time of diagnosis. WGS confirmed that all virus strains were VOC 202012/01-lineage B.1.1.7, suggesting a common source of exposure. Epidemiological investigation revealed that the suspected source was a SARS-CoV-2-positive patient who required endotracheal intubation due to severe COVID-19. All procedures were carried out using a full suite of personal protective equipment (PPE). Loconsole 2021 https://doi.org/10.1016/j.cmi.2021.05.007 doi:10.1016/j.cmi.2021.05.007 pmid:33984489 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 1422 test-positive were Alpha. Two dose vaccine efficacy against Alpha was 98.4% [96.9-99.1%], one dose VE was 90.1% (82.9-94.2%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection, sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Alpha (B.1.1.7) has an IC50 fold change of 1.19x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.7 pseudotyped virus model impairs binding by RBD-directed mAb 910-30. B.1.1.7 pseudotyped virus model abolishes N-terminal-domain-directed mAbs 5-24, 4-8, and 4A8. B.1.1.7 pseudotyped virus model impairs binding by N-terminal-domain-directed mAbs 2-17, 4-19, 5-7. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x improvement in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. 2x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.1.7). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 pmid:33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) aerosolization Alpha variant cases in a large campus study showed fine-aerosol shedding amongst unmasked participants remained significantly greater for alpha variant infections (18-fold, 95% CI, 3.4 to 92-fold) after adjusting for the increased viral RNA in MTS and saliva, the number of coughs during sampling sessions, and symptom. After controlling for the effect of masks and numbers of coughs during sampling, alpha variant infection was associated with a 100-fold (95% CI, 16 to 650-fold) increase in coarse- and a 73-fold (95% CI, 15 to 350-fold) increase in fine-aerosol RNA shedding. Adenaiye 2021 https://doi.org/10.1093/cid/ciab797 doi:10.1093/cid/ciab797 pmid:34519774 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability No differences in the stability of B.1.1.7 observed in the absence of simulated sunlight at either 20°C or 40°C (with a mean time for a 90% loss of viral infectivity across all dark conditions of 6.2 hours). However, a small but statistically significant difference in the stability was observed in simulated sunlight at 20°C and 20% relative humidity, with B.1.1.7 restoring wild type 90% loss time of 11 minutes vs. 7 and 8 minutes for B.1.319 (D614G) and B.28 (V367F) early 2020 viruses respectively. Schuit 2021 https://doi.org/10.1093/infdis/jiab171 doi:10.1093/infdis/jiab171 pmid:33822064 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Modelling the Alpha variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 3.9x relative to wild type (5.4 vs 1.4). This is less efficient than Delta (11x vs wildtype using a P681R mutation instead). [del ~144 changed due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a co-infection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant. Liu 2021 https://doi.org/10.1101/2021.08.12.456173v3 doi:10.1101/2021.08.12.456173v3 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant difference in T-cell response to B.1.1.7 was observed (vs. ancestral) in blood drawn from 28 participants received the Pfizer-BioNTech vaccine and 2 received the Moderna vaccine. This is despite three mutations (Y144del, D614G, and P681H) overlapping T-cell epitope hotspots. Woldemeskel 2021 https://doi.org/10.1172/JCI149335 doi:10.1172/JCI149335 pmid:33822770 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks. Meister 2021 https://doi.org/10.1093/infdis/jiab260 doi:10.1093/infdis/jiab260 pmid:33993274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The NAb titers (PRNT50) of sera collected from 38 vaccine recipients four-weeks after the second dose of inactivated whole-virion SARS-CoV-2 BBV152/COVAXIN vaccine [which contains D614G] were not significantly different between B.1.1.7 virus and ancestral D614G virus. Sapkal 2021 https://doi.org/10.1093/jtm/taab051 doi:10.1093/jtm/taab051 pmid:33772577 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy PBMCs of Pfizer/BioNTech BNT162b2 (n=8) 12-15 days post booster and Moderna mRNA-1273 COVID-19 vaccines (n=11) 13-30 days post-booster were stimulated with the Spike 15-mer peptide pools (w/ 10 residue overlaps), and showed no significant CD4+ cell count effect for B.1.1.7, and a slight increase in CD8+ percentage (p=0.0314) by Activation Induced Marker (AIM) assay (cellular immunity measurement). No signficant change in IF-gamma or IL-5 spot forming cell counts were observed. Tarke 2021 https://doi.org/10.1101/2021.02.27.433180 doi:10.1101/2021.02.27.433180 pmid:33688655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness [symptomatic or asymptomatic in cohort opf routinely NAAT-monitored UK HCWs] of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This cohort was vaccinated when the dominant variant in circulation was B.1.1.7 and demonstrates effectiveness against this variant. Hall 2021 https://doi.org/10.1016/S0140-6736(21 doi:10.1016/S0140-6736(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Between December 19, 2020 and Jan 24, 2021, 7214 of 9109 eligible HCWs at Sheba Medical Center in Israel had received one or more doses of BNT162b2 (Pfizer) vaccine. Adjusted rate reduction in SARS-CoV-2 NAAT positivity infection compared with unvaccinated workers 1-14 days after 1st dose was 30% (95% CI: 2-50), and 75% (95% CI: 72-84) after 15-28 days. Adjusted rate reduction in symptomatic COVID-19 compared with unvaccinated workers 1-14 days after 1st dose was 47% (95% CI: 17-66), and 85% (95% CI: 71-92) after 15-28 days. [Though often cited as an indicator of VE for B.1.1.7, during this time period in Israel, the prevalence of the B.1.1.7 variant increased from ~20% to 50% of cases (covariants.org), therefore these VE numbers likely represent a mix of B.1.1.7 and other lineage effects.] Amit 2021 https://doi.org/10.1016/S0140-6736(21 doi:10.1016/S0140-6736(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We found that a single dose of the BNT162b2 vaccine is about 60-70% effective at preventing symptomatic disease in adults aged 70 years and older in England and that two doses are about 85-90% effective. Those who were vaccinated and went on to have symptoms had a 44% lower risk of being admitted hospital and a 51% lower risk of death compared with people who were unvaccinated. We also found that a single dose of the ChAdOx1-S vaccine was about 60-75% effective against symptomatic disease and provided an additional protective effect against hospital admission—it is too early to assess the effect on mortality. The B.1.1.7 variant now dominates in the UK and these results will largely reflect vaccine effectiveness against this variant. Lopez Bernal 2021 https://doi.org/10.1136/bmj.n1088 doi:10.1136/bmj.n1088 pmid:33985964 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the 47D10. Alpha (B.1.1.7) has an IC50 fold change of 0.40x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events First documented cases of domestic cat and dog infections with the B.1.1.7 strain. Hamer 2021 https://doi.org/10.1111/tbed.14122 doi:10.1111/tbed.14122 pmid:33955193 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (48.7%; 95% confidence interval [CI], 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among those with the alpha variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among those with the alpha variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 pmid:34289274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA2-15 (~9x), B38 (~14x), S309 (~190x) by this B.1.1.7 pseudotyped virus model. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy We observed a sharp decline in cases when ∼50% of the elderly population was 2 weeks beyond their first vaccination dose and at a time point during which the B.1.1.7 variant gained transmission dominance. In support of this finding, it was suggested that, after the first vaccination dose, more than 70% of patients develop neutralization antibodies,15 and the vaccine efficiency can reach 85%. Munitz 2021 https://doi.org/10.1016/j.xcrm.2021.100264 doi:10.1016/j.xcrm.2021.100264 pmid:33899031 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralizing antibody titers of 2/20 (10%) samples showed >10x reduction (sera collected ~1mo post Jan 2020 first wave in China). Neutralizing antibody titers of 8/20 samples (40%) decreased below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China). Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Lessens the potency of mAbs COVA2-17 (~5x, similar to N501Y alone), COVA1-12 (~11x) and COVA1-21 (>100x), which do not compete allosterically. Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020. Possible reinfections were identified in 249 (0.7% [95% CI 0.6-0.8]) of 36509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Graham 2021 https://doi.org/10.1016/s2468-2667(21 doi:10.1016/s2468-2667(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.7 virus has reduced neutralization activity vs wild type: 2.1x (30 sera Pfizer median 9 days post 2nd dose) and 2.3x (35 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Note that Y145del was actually noted in the paper as the effect of their DNA construct, but this is equivalent at the protein level to the more commonly annotated Y144del. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The sera of 16 individuals with time course collection was evaulated against VSV pseudotypes: neutralized D614G at week 2, whereas B.1.1.7 started to be neutralized at week 3, although less efficiently than D614G. B.1.1.7 and D614G strains were similarly neutralized at week 4 (1 week after booster dose). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization assays of B.1.1.7 virus showed a reduction of 2.5-fold (14 days post 2nd dose AstraZeneca, n=15), 2.1-fold (28 days post 2nd dose AstraZeneca, n=10), and 3.3-fold (7-17 days post 2nd dose Pfizer-BioNTech, n=25). [D1119H was included in the original paper, assumed typographical error and changed to D1118H] Supasa 2021 https://doi.org/10.1016/j.cell.2021.02.033 doi:10.1016/j.cell.2021.02.033 pmid:33743891 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.39x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in early 2021 when Alpha was prevalent, vaccine efficacy was estimated as: mRNA-1273 86% (95%CI: 81-90.6%) and BNT162b2: 76% (95%CI: 69-81%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. [variant list included is ancestral Alpha, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 pmid:34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects ~20x resistence to mAb CQ038 by B.1.1.7 pseudotyped virus Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Reinfection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in an immunocompromised 16yo female with end stage renal disease 94 days after initial infection with a B.1.2 lineage virus. Both lineages were the prevalent one at the time of 1st and 2nd infections respectively in Texas, where the patient was located (suggesting exposure risk rather than lineage immune evasion). Marquez 2021 https://doi.org/10.1017/ice.2021.195 doi:10.1017/ice.2021.195 pmid:33934744 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Alpha Variant B.1.1.7 RBD significantly better than GenScript IgG FL18-740 w.t. ACE-2 mAB. Determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Alpha (B.1.1.7) has an IC50 fold change of 1.44x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A single dose of BNT162b2 (Pfizer) vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort (8203 treatment, 15121 control) was vaccinated when the dominant variant in circulation was B.1.1.7 and shows effectiveness against this variant. Hall 2021 https://doi.org/10.1016/S0140-6736(21 doi:10.1016/S0140-6736(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape NTD-specific nAbs showed a substantial (3-450x) decrease in neutralization potency against the recently reported highly transmissible B.1.1.7 variant of concern, whereas RBD-specific nAbs were either unaffected or showed lower decreases in potency. Graham 2021 https://doi.org/10.1016/j.immuni.2021.03.023 doi:10.1016/j.immuni.2021.03.023 pmid:33836142 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Alpha Molnupiravir (MK-4482) had ~2.75x fold drop. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 pmid:35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.7 reduced 1.2x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Second infection in December 2020 with B.1.1.7 after April 2020 initial infection with B.2 in a 78-year-old man with a history of Type 2 diabetes mellitus, diabetic nephropathy on hemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnea, ischemic heart disease, with no history of immunosuppression. Harrington 2021 https://doi.org/10.1093/cid/ciab014 doi:10.1093/cid/ciab014 pmid:33421056 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 1 (B.1.1.7) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2. Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~2.5x cleavage of S2 relative to WA1 (D614G) wildtype by Alpha variant variant as measured by mass spectrometry of Vero-TMPRSS culture. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Virus neutralisation activity (using a live SARS-CoV-2 microneutralisation assay (ND50)) by vaccine induced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B.1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Emary 2021 https://doi.org/10.2139/ssrn.3779160 doi:10.2139/ssrn.3779160 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Alpha (B.1.1.7) variant is 1.0x fold the wildtype in 42 COVI. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 15.4% in this B.1.1.7 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 pmid:33972942 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.1x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 (n=15) and day 14 (n-14) post-2nd dose) against a B.1.1.7 variant (USA/CA_CDC_5574/2020 [USA/CA-SEARCH-5574/2020?]) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 pmid:33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.1.7 pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed no statistically sognificant change in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 pmid:33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy NVX-CoV2373 [Novavax] vaccine in phase 3 trial was 89.7% (95% CI, 80.2-94.6) effective in preventing COVID-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8-99.5) and 86.3% (71.3-93.5) against the prototype strain and B.1.1.7 variant, respectively. Heath 2021 https://doi.org/10.1101/2021.05.13.21256639 doi:10.1101/2021.05.13.21256639 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.1.7 Spike variants lentivirus. 3.5x reduction in neutralization with Moderna vaccinated patient sera after 29 days (1st dose). 2.0x reduction in neutralization with Moderna vaccinated patient sera after 57 days (2nd dose). 2.1x reduction in neutralization with Novavax Phase 1 post-vaccination sera. Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) clinical indicators After adjusting for the age factor, in a prospective Chinese cohort study B.1.1.7 variant infection (compared to B.1.140) was the risk factor for C-reactive protein (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), Serum amyloid A (0.011, 5.031, [1.459, 17.354]), Creatine Kinase (0.034, 4.34, [0.05, 0.91]), CD4+ T lymphocyte (0.029, 3.31, [1.13, 9.71]), and Ground Glass Opacity (0.005, 5.418, [1.656, 17.729]) Song 2021 https://doi.org/10.1101/2021.05.04.21256655 doi:10.1101/2021.05.04.21256655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%). Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Live virus was tested ex vivo in reconstituted brochial epithelium, and out competed wild type. Touret 2021 https://doi.org/10.1101/2021.03.22.436427 doi:10.1101/2021.03.22.436427 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 1.7x reduction of NT50 value B.1.1.7 (Alpha) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Flow cytometry was used on recombinant VSV proteins and yeast surface display to assess the binding of a labeled soluble ACE2 protein to cells expressing B.1.1.7. We observed a dramatic increase (relative to D614G) in binding of soluble ACE2 to B.1.1.7, and to a lesser extent to B.1.351, which both carry the N501Y mutation (see Fig 3). Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM for binding to the Alpha B1.1.7. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy , Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,23709,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,T716I,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.1.7 lineage effectiveness was observed as 29.5% (95% CI [22.9,35.5]) against infection, and 54.1% against severe/critical/fatal disease (95% CI [26.1-71.9]). Two weeks or more after 2nd dose, effectiveness climbed to 89.5% [85.9,92.3] against infection, and 100% against severe/critical/fatal disease (95% CI [81.7,100]). , Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,24506 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,S982A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Lilly's LY-CoV16 showed marked reduction in neutralization of B.1.1.7. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 pmid:33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23604,23604,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Sera neutralized the B1.1.7 isolate with a lower potency (2-fold; 95% CL: 1.5 – 3-fold), and those with the lowest homotypic neutralizing potency had undetectable heterotypic potency (2/25). Skelly 2021 https://doi.org/10.21203/rs.3.rs-226857/v1 doi:10.21203/rs.3.rs-226857/v1 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23399,23401,23401,23402,23403,23403,23709,23604,23604,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,D614G,D614G,D614G,D614G,D614G,D614G,T716I,P681H,P681H,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific replication effects In this report, by using a lower infectious dose, we demonstrate that B.1.1.7 (cultured sample Hong Kong/HKPU-00015/2021) exhibits higher infectivity and/or replication efficiency in the nasal epithelium. (Hamster model of infection) Mok 2021 https://doi.org/10.1101/2021.04.19.440414 doi:10.1101/2021.04.19.440414 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralization capacity GMT of 27 subjects' sera post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 20/29 sera after the first dose of Pfizer showed an average reduction in neutralization titres against the B.1.1.7 variant of 3.2 ± 5.7. After the second dose, the GMT was markedly increased compared with the first-dose titres, with a fold change of 1.9 ± 0.9 (mean ± s.d.). Neutralization GMT of 27 subjects post-infection was considerably higher (stronger) than after the second Pfizer dose, and 4.5x drop in B.1.1.7 neutralization was observed. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility We estimate that this [B.1.1.17] variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. Data from other countries yield similar results: we estimate that R for VOC 202012/01 relative to other lineages is 55% (45–66%) higher in Denmark, 74% (66–82%) higher in Switzerland, and 59% (56–63%) higher in the United States, with consistent rates of displacement across regions within each country. Davies 2021 https://doi.org/10.1126/science.abg3055 doi:10.1126/science.abg3055 pmid:33658326 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Lineage B.1.1.7 spike–pseudotyped VSV was tested for neutralization vs Wuhan reference genome pseudotype in 40 sera collected 7 or 21 days post-booster dose. Statistically significant change (22%) in neutralization was observed among the 26 sera from those <=55yo, but not in the 14 sera from those >55yo. A ~20% change is not considered immunologically significant historically in influenza antibody studies. Muik 2021 https://doi.org/10.1126/science.abg6105 doi:10.1126/science.abg6105 pmid:33514629 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility At the national level (Italy), we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). Stefanelli 2021 https://doi.org/10.1101/2021.04.06.21254923 doi:10.1101/2021.04.06.21254923 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.1.7 defining mutations: Significant shift to asymptomatic cases (27.4% vs 18.6% for non-VOC cases). Significant shift to infection in those without pre-existing conditions (44.8% vs 89% for non-VOC cases). Significant increase in hospitalization rate (11% vs 7.5% for non-VOC cases). Significant increase in ICU rate (1.4% vs 0.6% for non-VOC cases). Significant decrease in death rate (2.0% vs vs 4.0% for non-VOC cases). Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 pmid:33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Oslo, Norway: Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants. Lindstrøm 2021 https://doi.org/10.1101/2021.03.29.21254122 doi:10.1101/2021.03.29.21254122 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Based on ∼300,000 RT-PCR samples collected from December 6th 2020 to February 10th 2021 in Israel, the B.1.1.7 is 45% (95% CI:20-60%) more transmissible than the wild-type strain, and become dominant in Israel within 3.5 weeks. Munitz 2021 https://doi.org/10.1016/j.xcrm.2021.100264 doi:10.1016/j.xcrm.2021.100264 pmid:33899031 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The matching-adjusted conditional odds ratio of hospitalisation was 1.58 (95% confidence interval 1.50 to 1.67) for COVID-19 patients infected with a SGTF-associated variant [primarily B.1.1.7], compared to those infected with non-SGTF-associated variants. The effect was modified by age (p<0.001), with ORs of 0.96-1.13 below age 20 years and 1.57-1.67 in age groups 40 years or older. Nyberg 2021 https://doi.org/10.48550/arXiv.2104.05560 doi:10.48550/arXiv.2104.05560 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using UK data 1 November 2020 to 14 February 2021, while correcting for misclassification of PCR test Spike Gene Target Failure (SGTF) and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Davies 2021 https://doi.org/10.1038/s41586-021-03426-1 doi:10.1038/s41586-021-03426-1 pmid:33723411 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load B.1.1.7 samples showed average Ct cycle threshold of 21.9 vs 23 for wildtype (i.e. ~2x higher viral load) comparing 37758 and 22535 samples respectively. Roquebert 2021 https://doi.org/10.1101/2021.03.19.21253971 doi:10.1101/2021.03.19.21253971 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Based on 36920 COVID Symptom Study app users reported SARS-CoV-2 test positivity in late 2020, Rt of B.1.1.7 was 1.35x (95% CI 1.02-1.69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Graham 2021 https://doi.org/10.1016/s2468-2667(21 doi:10.1016/s2468-2667(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio 341 samples collected Nov 9 to Dec 20, 2020 were sequenced from two London (UK) hospitals. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. No evidence was found of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). Frampton 2021 https://doi.org/10.1016/s1473-3099(21 doi:10.1016/s1473-3099(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. Graham 2021 https://doi.org/10.1016/s2468-2667(21 doi:10.1016/s2468-2667(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 249 B.1.1.7 (a.k.a. N501Y.V1) variant cases in three Paris hospital labs had a ~10-fold viral load increase (~3.3 Ct drop in N gene probe) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). PG: BUT there is a discrepancy in drop between the ORF1ab and N probes, with the former suggesting only a 2-fold drop, consistent with the drop observed in B.1.351. This might indicate higher subgenomic RNA content in B.1.1.7 skewing the change. Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Using lack of S probe detection as a proxy for B.1.1.7 status, 275 putative B.1.1.7 samples and 390 'wild type' SARS-CoV-2 positive samples in Wales were compared for Ct values, suggesting ~12-fold increase (~3.5 Ct decrease) in viral load for B.1.1.7 samples. Couzens 2021 https://doi.org/10.1101/2021.04.02.21254832 doi:10.1101/2021.04.02.21254832 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio The mortality hazard ratio associated with infection with [B.1.1.7] compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community (54906 matched pairs of participants who tested positive for SARS-CoV-2 in pillar 2 between 1 October 2020 and 29 January 2021). In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases. Challen 2021 https://doi.org/10.1136/bmj.n579 doi:10.1136/bmj.n579 pmid:33687922 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load In a study of 1260 ICU subjects, viral load distributions (collected within 48h of admission) were elevated in both seropositive and seronegative subjects infected with B.1.1.7 ('UK variant'). PG: The PANGO tool defining Spike variants for B.1.1.7 are listed here, whereas the paper only used a test for D1118H. Ratcliff 2021 https://doi.org/10.1101/2021.02.24.21251989 doi:10.1101/2021.02.24.21251989 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load This study reveals that B.1.1.7 SARS-CoV-2 variant is a slower-growing virus than parental B.1. Further, a higher replication along with reduced infectious viral titer was hypothesized to be linked to higher transmission with reduced pathogenicity. Nyayanit 2021 https://doi.org/10.1101/2021.04.30.442222 doi:10.1101/2021.04.30.442222 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Lamers 2021 https://doi.org/10.1101/2021.05.03.441080 doi:10.1101/2021.05.03.441080 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Danish study of the B.1.1.7 lineage shows hospital admission odds ratio of 1.63 vs other lineages. The adjusted OR was increased in all strata of age. Bager 2021 https://doi.org/10.2139/ssrn.3792894 doi:10.2139/ssrn.3792894 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Ontario, Feb 2021: The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49) Buchan 2021 https://www.medrxiv.org/content/10.1101/2021.03.31.21254502v1 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036). Song 2021 https://doi.org/10.1101/2021.05.04.21256655 doi:10.1101/2021.05.04.21256655 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5-1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load. Lyngse 2021 https://doi.org/10.1101/2021.04.16.21255459 doi:10.1101/2021.04.16.21255459 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.1.7 showed 1.77-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was unchanged. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 5.2-fold against B.1.1.7 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 pmid:33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Using primarily S-defining mutations for lineage B.1.1.7, most models of hospitalization and fatality risk ratios from consortium members show elevated ratios (~1.3-1.7x). 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/961042/S1095_NERVTAG_update_note_on_B.1.1.7_severity_20210211.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking VSV pseudotype B.1.1.7 showed no significant difference in cell entry relative to wild type in 6 cell lines. Cell fusion proficiency was unchanged. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Six fold increase in affinity for ACE2 by the B.1.1.7 lineage vs wild type is driven by a drop in observed dissociation rate constant. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 1 hour. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation set from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing significant (40%) increase in infection rate amongst the cells, much more than the effect of either the deletion or the point mutation alone, suggetsing that this combination has a synergistic effect contributing to cell entry fitness, but to a smaller extent than N501Y and the deletion alone. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding These key B.1.1.7 mutations as a combination neutralized slightly less well than D614G and this was noticeable in the lack of sera with high neutralizing titer for the viruses across 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Slight neutralization improvement on average in 16 health workers' convalescent sera. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation combination, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23604,23604 H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,P681H,P681H YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape One convalescent sera tested showed 4-fold or greater reduction in neutralization efficiency. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,22679,22679,24465,24466,24466,24468,24469,23521,23521,23522,23524,23524,23525,23525,22194,22197,22198,22198,22199,22200,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21641,24421,24421,24422,24423,24424,24424,24424,23060,23061,23062,23062,23063,23063,21594,21603,21603,21614,21617,21617,21618,21618,22879,22879,22881,22882,22882,22882,23595,23596,23596,23598,23599,23853,23854,23854,23071,23071,23074,23074,23075,23075,23944,23944,23946,23947,23948,23948,22992,22995,22671,22672,22672,22673,22674,22810,22810,22811,22812,22813,22813,22813,23018,22576,22577,22578,22783,22783,22784,22785,22786,22786,23604,23604,22686,22771,22775,22775,23053,23053,23054,23054,23055,23055,22992,23009,23010,23012,23013,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 H69del,H69del,S373P,S373P,N969K,N969K,N969K,N969K,N969K,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,V213G,V213G,V213G,V213G,V213G,V213G,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A27S,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,N440K,N440K,N440K,N440K,N440K,N440K,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,T478K,T478K,S371F,S371F,S371F,S371F,S371F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,R408S,P681H,P681H,S375F,D405N,D405N,D405N,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 17.2x-fold lower (95% CI: 0.6x-0.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,22679,22679,24465,24466,24466,24468,24469,23521,23521,23522,23524,23524,23525,23525,22194,22197,22198,22198,22199,22200,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21641,24421,24421,24422,24423,24424,24424,24424,23060,23061,23062,23062,23063,23063,21594,21603,21603,21614,21617,21617,21618,21618,22879,22879,22881,22882,22882,22882,23595,23596,23596,23598,23599,23853,23854,23854,23071,23071,23074,23074,23075,23075,23944,23944,23946,23947,23948,23948,22992,22995,22671,22672,22672,22673,22674,22810,22810,22811,22812,22813,22813,22813,23018,22576,22577,22578,22783,22783,22784,22785,22786,22786,23604,23604,22686,22771,22775,22775,23053,23053,23054,23054,23055,23055,22992,23009,23010,23012,23013,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 H69del,H69del,S373P,S373P,N969K,N969K,N969K,N969K,N969K,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,V213G,V213G,V213G,V213G,V213G,V213G,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A27S,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,T19I,T19I,T19I,T19I,T19I,T19I,T19I,T19I,N440K,N440K,N440K,N440K,N440K,N440K,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,T478K,T478K,S371F,S371F,S371F,S371F,S371F,K417N,K417N,K417N,K417N,K417N,K417N,K417N,F486V,G339D,G339D,G339D,R408S,R408S,R408S,R408S,R408S,R408S,P681H,P681H,S375F,D405N,D405N,D405N,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,S477N,E484A,E484A,E484A,E484A,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Val213Gly,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Thr19Ile,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Phe486Val,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, BA.4/5 (from ) were 13.0-fold lower (95% CI: 4.2x-4.6x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,22810,22810,22811,22812,22813,22813,22813,23009,23010,23012,23013 H69del,H69del,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484A,E484A,E484A,E484A YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Ontario, using a retrospective matched case (age, gender and onset date) study of 6,312 Omicron cases vs 8,875 Delta, the adjusted risk of hospitalization or death was 54% lower (HR=0.46, 95%CI: 0.27, 0.77) among Omicron cases, after adjusting for vaccination statis and time since 2nd shot. The ratio for >60yo was 0.55 (95%CI: 0.28-1.06), and <60yo was 0.30 (95%CI: 0.16-0.57). Ulloa 2021 https://doi.org/10.1101/2021.12.24.21268382 doi:10.1101/2021.12.24.21268382 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21763,21764,23009,23010,23012,23013 H69del,H69del,E484A,E484A,E484A,E484A NC_045512.2(GU280_gp02):g.204_209del,NC_045512.2(GU280_gp02):g.204_209del,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Population-level evidence suggests that the Omicron variant is associated with substantial ability to evade immunity from prior infection, evidenced by a reinfection hazard ratio of 2.39 (CI95: 1.88-3.11) relative to primary infection in the initial part of South Africa's 4th covid-19 wave (November 2021). In contrast, there is no population-wide epidemiological evidence of immune escape associated with the Beta or Delta variants. [minimal variant signature for Omicron (B.1.1.529) used based on H69del PCR dropout observed in November 2021 coincident with the rise of Omicron] Pulliam 2021 https://doi.org/10.1101/2021.11.11.21266068 doi:10.1101/2021.11.11.21266068 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21786,21786,21789,22298,22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403,24138 G75V,T76I,T76I,R246_D253delinsN,L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G,T859N YP_009724390.1:p.Gly75Val,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Arg246_Asp253delinsAsn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr859Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 1.7x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21786,21786,21789,22298,22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403,24138 G75V,T76I,T76I,R246_D253delinsN,L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G,T859N YP_009724390.1:p.Gly75Val,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Arg246_Asp253delinsAsn,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr859Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 3.4x reduction of NT50 value for C.37 (Lambda) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21786,21786,21789,22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403,24138,22298 G75V,T76I,T76I,L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G,T859N,R246_D253delinsN YP_009724390.1:p.Gly75Val,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr859Asn,YP_009724390.1:p.Arg246_Asp253delinsAsn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.048x fold change in IC50 in C.37 Lambda Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21786,21786,21789,22917,23027,23029,23029,23030,23031,23031,23399,23401,23401,23402,23403,23403,24138,22298 G75V,T76I,T76I,L452Q,F490S,F490S,F490S,F490S,F490S,F490S,D614G,D614G,D614G,D614G,D614G,D614G,T859N,R246_D253delinsN YP_009724390.1:p.Gly75Val,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Thr76Ile,YP_009724390.1:p.Leu452Gln,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr859Asn,YP_009724390.1:p.Arg246_Asp253delinsAsn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.038x fold change in IC50 in C.37 Lambda Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800 D80Y NC_045512.2(GU280_gp02):g.238G>T YP_009724390.1:p.Asp80Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This AA substitution outside the receptor binding domain in pseudotyped VSV promoted a 7.2% transduction rate in golden hamster cells, which was higher than that of human epithelial-like Huh-7 cells (6.6%). Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800 D80N NC_045512.2(GU280_gp02):g.238G>A YP_009724390.1:p.Asp80Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21800,22188,22206,22302,22335,22597,22597,22599,23011,23012,23521,23521,23522,23524,23524,23525,23525,23604,23604 D80Y,I210del,D215G,Y248del,W258L,R346K,R346K,R346K,E484K,E484K,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,P681H,P681H YP_009724390.1:p.Asp80Tyr,YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Tyr248del,YP_009724390.1:p.Trp258Leu,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against A.VOI.V2 (first identified in Angola) reduced 8.0x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2(GU280_gp02):g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 pmid:34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2(GU280_gp02):g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated that there is no free energy change (ddG) for this variant (i.e. same stability as wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2(GU280_gp02):g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2(GU280_gp02):g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion One individual of 30 in the study, with HLA supertype HLA*A24:02, had a linear epitope that overlaps this variant of concern. Redd 2021 https://doi.org/10.1101/2021.02.11.21251585 doi:10.1101/2021.02.11.21251585 pmid:33594378 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801 D80A NC_045512.2(GU280_gp02):g.239A>C YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abolishes neutralizing activity of N-terminal-domain-directed mAb 4-19. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~10-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~3 fold without the deletion] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were significant, but ~500x weaker than in previously infected patients after first dose. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 pmid:33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Detectable antibodies against B.1.351 at various time points using pseudotyped lentivirus neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 71%, Day 209 54%. Detectable antibodies against B.1.351 at various time points using live virus FRNT neutralization in Moderna vaccinee cohort: Day 29 8%, Day 43 100%, Day 119 79%, Day 209 58%. Detectable antibodies against B.1.351 at various time points using ACE2 blocking assay in Moderna vaccinee cohort: Day 29 63%, Day 43 100%, Day 119 71%, Day 209 79%. Decreased neutralization on some assays was seen especially in those vaccinees tested that were 71+. Pegu 2021 https://doi.org/10.1101/2021.05.13.444010 doi:10.1101/2021.05.13.444010 pmid:34031659 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In an Ontario long term care facility, cumulatively, weaker BNT162b2 vaccine stimulation, age/comorbidities, produced a ∼130-fold reduction in apparent neutralization titers in mean 88yo LTCH residents against Beta (B.1.351), relative to staff vaccinees against D614G wild type. 37.9% of 116 two-dose-mRNA-vaccinated residents had undetectable neutralizing antibodies to B.1.351. mRNA-1273 vaccinee sera displayed ~2 better neutralization than BNT162b2. [common defining B.1.351 mutations noted, as the manuscript does not provide details] Abe 2021 https://doi.org/10.1101/2021.08.06.21261721 doi:10.1101/2021.08.06.21261721 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 pmid:33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, 7 of 15 neutralized this B.1.351 pseudotype that includes the L242del, and only one had titers above 100. Only one of the 15 sera achieved 80% neutralization. [compare to 5 and 1 for pseudotype without the deletion] Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 pmid:33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.351 was 3.4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 2.2-fold resistant. [Exact list of B.1.351 mutations used in these assays was not included in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Beta (B.1.351) has an IC50 fold change of 0.13x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Beta Molnupiravir (MK-4482) had ~1.75x fold drop. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 pmid:35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The B.1.351 variant constellation causes an ∼20-fold increase in affinity for ACE2 compared with Wuhan RBD, which may influence transmissibility. Zhou 2021 https://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 pmid:33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) humoral response durability In a prospective study of 107 hospitalized patients, decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7 and P.1 variants for at least 6 months (last of two samples taken) in patients previously hospitalized for COVID-19. A weaker protection was however observed for the B.1.351 variant. Betton 2020 https://doi.org/10.1093/cid/ciab308 doi:10.1093/cid/ciab308 pmid:33851216 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~6x cleavage of S2 relative to WA1 (D614G) wildtype by Beta variant as measured by mass spectrometry of Vero-TMPRSS culture [no mutations directly at furin cleavage site, but A701V is downstream] Compare to 4.5x or less for variants of concern with direct furin clevage site mutations. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio Compared to Alpha (B.1.1.7) variant, odds of progressing to severe disease were 1.24-fold (95% CI: 1.11-1.39) higher for Beta. Odds of progressing to critical disease were 1.49-fold (95% CI: 1.13-1.97) higher. Odds of COVID-19 death were 1.57-fold (95% CI: 1.03-2.43) higher. Abu-Raddad 2021 https://doi.org/10.1101/2021.08.02.21261465 doi:10.1101/2021.08.02.21261465 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Beta (B.1.351) variant is 0.4x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 34 convalescent cases 4–9 weeks following infection in June 2020, before the emergence of B.1.1.7, neutralization titers against B.1.351 were, on average, 13.3-fold reduced compared with an early Victoria sample (p < 0.0001). Significantly, 18 of 34 samples failed to reach 50% neutralization at a plasma dilution of 1:20, with a number showing a near total reduction of neutralization activity. In 13 convalescent cases 4–9 weeks following infection with B.1.1.7, neutralization titers against B.1.351 were, on average, 3.1-fold reduced compared with an early Victoria sample (p < 0.0001). Zhou 2021 https://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 pmid:33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Beta (B.1.351) has an IC50 fold change of 0.15x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccine plasma neutralization of B.1.351-spike virus was nominally robust but lower (~3x) than other variants of concern. Liu 2021 https://doi.org/10.1056/NEJMc2102017 doi:10.1056/NEJMc2102017 pmid:33684280 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.1.351-v3 reduced 8.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Testing against B.1.351 the 20 most effective mAbs (19 anti-RBD, 1 anti-NTD) from a screen of 377 against wild type, 4 of 20 antibodies had >10-fold fall in neutralization titers, with most of these showing a complete knockout of activity. This is in line with the key roles of K417, E484, and N501, in particular E484, in antibody recognition of the ACE2 interaction surface of the RBD. Regeneron mAb cocktail: The neutralization of REGN10987 was unaffected by B.1.351, while REGN10933 was severely impaired (773-fold). AstraZeneca mAb cocktail: Neutralization by the AZ pair of antibodies was little affected on B.1.351 compared with Victoria. Zhou 2021 https://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 pmid:33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy A two-dose regimen of (AstraZeneca) ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, vaccine efficacy against severe Covid-19 is undetermined. Madhi 2021 https://doi.org/10.1101/2021.02.10.21251247 doi:10.1101/2021.02.10.21251247 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The Janssen single dose vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa, where 92.6% of infections are estimated to have been B.1.351. 100% reduction in hospitalization risk remains across variants after 28 days post-vaccination. Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Unlike wild type or B.1.1.7, B.1.351 lineage virus was able to infect and replicate in common lab mouse strains, with high titer. PG: The virus used in these expriments has a non-typical deletion+sub in the 242 region. Montagutelli 2021 https://doi.org/10.1101/2021.03.18.436013 doi:10.1101/2021.03.18.436013 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Beta (B.1.351) has an IC50 fold change of 0.13x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera from healthcare workers (n = 25) 4–17 days following the second dose of Pfizer vaccine, administered 3 weeks after the first dose, showed geometric mean titers for B.1.351 7.6-fold lower than for an early Victoria sample (p < 0.0001). For the AstraZeneca vaccine, samples (n = 25) were obtained 14 or 28 days following the second vaccine dose, with a dosing interval of 8–14 weeks, geometric mean B.1.351 titers were 9-fold lower than for Victoria (p < 0.0001). Zhou 2021 http://doi.org/10.1016/j.cell.2021.02.037 doi:10.1016/j.cell.2021.02.037 pmid:33730597 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Beta (B.1.351) has an IC50 fold change of 0.88x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio On average across 7 European countries studied, using B.1.351 defining mutations: Significant shift to infection in those without pre-existing conditions (79.6% vs 89% for non-VOC cases). Significant increase in hospitalization rate (19.3% vs 7.5% for non-VOC cases). Significant increase in ICU rate (2.3% vs 0.6% for non-VOC cases). PG: seems to be different notations around the LAL deletion, using the minimal shared definition to catch as many as possible. Funk 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.16.2100348 doi:10.2807/1560-7917.ES.2021.26.16.2100348 pmid:33890566 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.351 v1 virus has reduced neutralization activity vs wild type: 34.5x (30 sera Pfizer median 9 days post 2nd dose) and 27.7x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy ELISpot assays show T cell neutralization reduced by 29.8% in this B.1.351 pseudotype relative to wild type in 18-20 pooled patient samples post second mRNA vaccine dose, with no significant difference between Pfizer and Moderna cohorts. Reduction was stronger in the S1 subunit than S2 (separate peptide pools were used). Gallagher 2021 https://doi.org/10.1101/2021.05.03.442455 doi:10.1101/2021.05.03.442455 pmid:33972942 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using B.1.351 defining mutations for Spike, observed 4x average decrease in neutralization efficiency (but still relevant titres) for sera from 10 BNT162b2 vaccinees 12 days after second dose, but only one relevant titre 12 days after first dose. Compares unfavorably to wild type or B.1.1.7 titres. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Using convalescent sera from 15 early pandemic patients (Seattle Flu Study), mean 220 days post symptom onset (IQR 125-269, and three asymptomatic cases) with 27% WHO disease severity scale 3, one third (5/15) of sera neutralized this B.1.351 pseudotype and only three had ID50 titers above 100. Only two of the 15 sera achieved 80% neutralization. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 pmid:33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera collected from 15 early pandemic patients (Seattle Flu Study), mean 16 days post first dose with either Pfizer/BioNTech or Moderna vaccines, the median ID50 titers were ~3-fold lower against this B.1.351 pseudotyped virus relative to wild type. A single asymptomatic patient, who had no detectable RBD-specific IgG memory before vaccination, also did not elicit nAbs against the B.1.351 variant. [compare to ~10 fold with L242del] ID50 titres in non-infected mRNA vaccines more than two weeks post-booster were signficiant, but >100x weaker than in previously infected patients after first dose. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 pmid:33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664,23399,23401,23401,23402,23403,23403 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Anti-NTD CV1 mAb isolated from an early pandemic case was unable to neutralize either partial B.1.351 variant pseudovirus used (A701V or L242del). The neutralization potency of mAb CV30, which contacts K417 and N501 but not E484, was ~10-fold weaker toward both B.1.351 variants. The neutralization potency of anti-RBD mAb CV3-1 was 3-4-fold less potent against the B.1.351 variants, while anti-RBD mAb CV2-75 was modestly less effective. Stamatatos 2021 https://doi.org/10.1126/science.abg9175 doi:10.1126/science.abg9175 pmid:33766944 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23664,23060,23061,23062,23062,23063,23063,23011,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 4 health care workers in the 20's and 30's with no underlying conditions and seropositivity or confirmed 2020 SARS-CoV-2 infections were confirmed to have B.1.351 infection during a Februrary 2021 hospital outbreak in Luxembourg. Symptoms were mostly mild on first infection, and milder on second infection. Staub 2021 https://doi.org/10.2807/1560-7917.ES.2021.26.18.2100423 doi:10.2807/1560-7917.ES.2021.26.18.2100423 pmid:33960291 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23664,23060,23061,23062,23062,23063,23063,23011,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Hamsters re-infected with B.1.351 virus after seroversion from previous infection with a lineage A virus did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. They had little infectious virus and no pathology in the lungs. Initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351, but prevents disease and onward transmission. Yinda 2021 https://doi.org/10.1101/2021.05.05.442780 doi:10.1101/2021.05.05.442780 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22206,22810,22810,22811,22812,22813,22813,22813,23664,23060,23061,23062,23062,23063,23063,23011,23012 D80A,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,A701V,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ala701Val,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence Inoculation with the B.1.351 isolate resulted in lower clinical scores in 6 rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. Our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity. Munster 2021 https://doi.org/10.1101/2021.05.07.443115 doi:10.1101/2021.05.07.443115 pmid:34382034 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped B.1.351 v3 virus has reduced neutralization activity vs wild type: 42.4x (30 sera Pfizer median 9 days post 2nd dose) and 19.2x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Notably, 36.7% (11/30) recipients of two-dose Pfizer and 42.9% (15/35) recipients of two-dose Moderna vaccines did not have detectable neutralization of at least one of the B.1.351 variants. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralization activities of two vaccines developed in China were tested against 501Y.V2 authentic virus: inactivated BBIBP-CorV (no significant change) and recombinant dimeric RBD vaccine ZF2001 (~1.6x reduction vs wildtype, p=0.04). Both vaccines largely preserved their neutralizing titres. Huang 2021 https://doi.org/10.1101/2021.02.01.429069 doi:10.1101/2021.02.01.429069 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Most of the plasma from 55 Pfizer vaccinees developed high percentages of Wuhan-Hu-1 S-ACE2 blocking activity, peaking at day 28 (7 days post-boost). A strikingly consistent hierarchy of reduction in plasma antibody binding by variant S and RBD antigens was observed among study participants, with progressively decreased binding for B.1.1.7 (not significant), P.1 (significant) and B.1.351 (significant) compared to Wuhan-Hu-1 antigens. Röltgen 2021 https://doi.org/10.1101/2021.04.05.21254952 doi:10.1101/2021.04.05.21254952 pmid:33851181 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy During an outbreak of SARS-CoV-2 501Y.V2 in a nursing home, all non-vaccinated residents (5/5) versus half of those fully vaccinated 2-5 weeks prior with BNT162b2 (13/26) were infected. Two of 13 vaccinated versus 4 of 5 non-vaccinated residents presented severe disease. BNT162b2 did not prevent the outbreak, but reduced transmission and disease severity. Among the 13 fully vaccinated residents who were infected, 2 (15.4%) presented with an asymptomatic disease, 9 (69.2%) developed mild to moderate symptoms, and 2 (15.4%) progressed to severe disease with fatal evolution secondary to acute respiratory distress syndrome (ARDS). There was no relationship between anti-S antibody levels at diagnosis and disease severity. Overall, the proportion of residents with severe disease in the non-vaccinated group (4/5) was higher than that in the vaccinated group (2/13). Only 1 vaccinated staff, but 10 unvaccinated were infected in the outbreak (no severe disease). Bailly 2021 https://doi.org/10.1093/cid/ciab446 doi:10.1093/cid/ciab446 pmid:33993228 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was significantly lower against B.1.351 in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In sera 1-2 weeks after BNT162b2 first dose, from six patients previously infected with B.1, antibody titer in a microneutralization assay was on average 1625 for B.1.351 virus. This compares favorably (stronger) to most post-infection neutralization titer against all variants tested in the same sera (wild type, B.1.1.7, B.1.351, and P.1). Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 pmid:33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.5x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received BBIBP-CorV (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the BBIBP-CorV vaccinee sera. >3x reduction in neutralization by serum collected 2 to 3 weeks after the second dose from vaccinees who had received CoronaVac (pVNT50 against VSV pseudotyped as B.1.351). Convalescent plasma had similar titer against wild type as the CoronaVac vaccinee sera. Wang 2021 https://doi.org/10.1056/NEJMc2103022 doi:10.1056/NEJMc2103022 pmid:33822491 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.351 variant constellation two-tailed Wilcoxon matched-pairs signed-rank test against 10 convalescent sera P=0.0020 for moderate resistance. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the B.1.351 lineage of SARS-CoV-2 in South Africa. The SA arms of the Phase 3 double blind study showed severe/critical disease VE of 73.1% (95% CI: 40.0-89.4), and moderate to severe/critical disease VE of 52.0% (95% CI: 30.3-67.4). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 66.9% of SA severe infections that have been sequenced as of this report, 94.5% are B.1.351. 2021 https://www.fda.gov/media/146217/download False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The dominant circulating B.1.351 spike variant originating in RSA, which harbors E484K and additional substitutions in the RBD, NTD, and S2 and deletions in the NTD (amino acids 242–244), was neutralized with a 5.02-fold reduced titer Solfrosi 2021 https://doi.org/10.1084/jem.20202756 doi:10.1084/jem.20202756 pmid:33909009 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape B.1.1.351 in 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects B.1.1.351 variant constellation ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. B.1.1.351 variant constellation ablates Class 3 N-terminal domain targeting antibodies COV2-2489 and COV2-2676 (the only two tested). Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In a Syrian hamster model, B.1.351 variant virus had >4x reduction in YRNT90 (measure of neutralization) using wild type convalescent sera. PG: Note that exact sequence for B.1.351 used was not disclosed. Cochin 2021 https://doi.org/10.1101/2021.04.19.440435 doi:10.1101/2021.04.19.440435 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 13 plasma collected ~1mo after B.1.1.7 infection (nursing home in Ticino, Switzerland), neutralization reduced to undetectable levels in many plasma for B.1.351 pseudotyped virus, as well as WT and other VOCs. [paper does not detail the B.1.351 variants used, using the most popular as a stad in] McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding VSV pseudotype B.1.351 showed 7.86-fold decrease in NT50 vs wild type in sera from 9 ICU patients undergoing treatment in Germany (pre-variant infections). Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abrogates Bamlanivimab, Etesevimab, or their combined use neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Approximately 6-fold reduction in 15 ICU patient convalescent plasma neutralization as quantified by measuring virus-encoded luciferase activity in cell lysates at 16-18 h post transduction. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccine elicited antibodies neutralized virus with the B.1.351 spike protein had an average 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In one of eight cell lines tested (293T lung cells), a modest increase in cell entry was observed. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees 6.5-fold against B.1.351 (contrast with 3.4 fold against original SARS-CoV-2). Leier 2021 https://doi.org/10.1101/2021.04.25.21256049 doi:10.1101/2021.04.25.21256049 pmid:33948601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness VSV pseudotype B.1.351 entry mediated by the S proteins of the B.1.351 variant was completely resistant to blocking by REGN10989 and Bamlanivimab. Entry driven by the S proteins of the B.1.351 was partially resistant against Casirivimab. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy B.1.351 pseudotyped lentivirus showed 3.4 and 3.8x reduction in IC50 serum dilution concentration for sera from BNT162b2 (Pzifer) or mRNA1273 (Moderna) vacinees collected 28 days following booster dose. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 pmid:33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy VSV pseudotype B.1.351 showed 7.85-fold reduction in neutralization efficiency vs wild type in 15 Pfizer BNT162b2 vaccinee sera 13-15 days post second dose. Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.351 (authentic cell culture supernatants). By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Study was 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 pmid:33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking VSV pseudotype B.1.351 showed slight decrease in cell entry relative to wild type in 263T-ACE2 (kidney) cell line, and slight increase in Calu-3 (lung). Cell fusion proficiency was slight impaired. Hoffman 2021 https://doi.org/10.1016/j.cell.2021.03.036 doi:10.1016/j.cell.2021.03.036 pmid:33794143 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding We analyzed 34 convalescent samples including the WHONIBSC 20/130 reference serum, and, although a few sera showed near identical FRNT 50 values, the FRNT50 dilutions for the B.1.1.7 strain were 2.9-fold lower (geometric mean) than those for the Victoria strain (p < 0.0001). Sera from 13 subjects post-B.1.1.7 infection showed no significant change in neutralization against Victoria (~wild type), suggesting that B.1.1.7 infection also protects against ancestral virus. [Note that D1119H was included in the original paper, assuming typographical error and correcting to D1118H] Supasa 2021 https://doi.org/10.1016/j.cell.2021.02.033 doi:10.1016/j.cell.2021.02.033 pmid:33743891 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy , Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 15 Pzifer non-senior vaccinee sera collected 3-4 weeks post-booster [using Table S1, not the text that says 2-3 weeks], neutralization was reduced ~11x. Hoffman 2021 https://doi.org/10.1101/2021.05.04.442663 doi:10.1101/2021.05.04.442663 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21801,22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23664 D80A,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A701V YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In Qatar, where Pfizer vaccine use is prevalent (<10% of the population covered in the time period of the study ending Mar 31, 2021), any time after one dose (including the 2 weeks where no major effect is expected) B.1.351 lineage effectiveness was observed as 16.9% (95% CI [10.4,23.0]) against infection, and 0% against severe/critical/fatal disease (95% CI [0-19.0]). Two weeks or more after 2nd dose, effectiveness climbed to 75.0% [70.5,78.9] against infection, and 100% against severe/critical/fatal disease (95% CI [73.7,100]). , Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775 T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.617.1-v1 ('Kappa') reduced 3.4x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22227,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1, Delta (B.1.617.2) shows mean 2.1x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22227,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 T95I,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A222V,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Relative to B.1, Delta (B.1.617.2) shows 3.64x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22131,22220,22272,22299 T95I,R190T,F220I,R237K,R246T NC_045512.2(GU280_gp02):g.284C>T,NC_045512.2(GU280_gp02):g.569G>C,NC_045512.2(GU280_gp02):g.658T>A,NC_045512.2(GU280_gp02):g.710G>A,NC_045512.2(GU280_gp02):g.737G>C YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg190Thr,YP_009724390.1:p.Phe220Ile,YP_009724390.1:p.Arg237Lys,YP_009724390.1:p.Arg246Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 65yo female with no severe Covid-19 risk factors tested positive 36 days after second dose of BNT162b2 (Pfizer) vaccine. Presented with fatigue, sinus congestion, and a headache developed; her symptoms plateaued and began to resolve six days later. [Mising genome coverage in regions of Spike covering clinically relevant mutations K417T, L452R, E484K, A701V, D796H, N501Y] Hacisuleyman 2021 https://doi.org/10.1056/NEJMoa2105000 doi:10.1056/NEJMoa2105000 pmid:33882219 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22317,22319,22320,23399,23401,23401,23402,23403,23403 T95I,D253G,D253G,D253G,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio B.1.526 (Iota) substantially increased IFR in older adults: by 46% (95% CI: 7.4 – 84%) among 45-64 year-olds, 82% (95% CI: 20 – 140%) among 65-74 year-olds, and 62% (95% CI: 45 – 80%) among 75+ during Nov 2020 – Apr 2021, compared to baseline IFR estimated for preexisting variants. [minimum clade defining mutations listed] Yang 2021 https://doi.org/10.1101/2021.08.04.21261596 doi:10.1101/2021.08.04.21261596 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Sera from vaccinees [ChAdOx1 and BNT162b2 primarily used in UK] shows decreased ability to neutralize B.1.621 compared to first wave virus and Alpha, with a magnitude of change similar to Beta. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 69 test-positive were Mu. Two dose vaccine efficacy against Mu was 90.4% (73.9-96.5%), one dose VE was 45.8% (0.0-88.9%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Sera from individuals who have been vaccinated and have had subsequent recent Delta infection have a high level of neutralising activity against B.1.621. 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Sera from individuals who have been infected with Delta does not have strong neutralising activity against B.1.621 2021 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In sera from six patients collected 1 to 12 weeks post-infection with B.1, antibody titer in a microneutralization assay was on average 71.46 for P.1 virus. Compare to much stronger neutralization titers for B.1.1.7 (256) and wild type (456.1) in the same sera. Luftig 2021 https://doi.org/10.1056/NEJMc2104036 doi:10.1056/NEJMc2104036 pmid:33826815 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24410 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D950N YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 7.6x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. [This is a greater reduction than Beta @ 6.3x] Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24410 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D950N YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using live B.1.621 virus and a cytopathic effect-based assay, sera from 37 Pfizer/BioNTech BNT162b2 vaccinees collected 10-20 days post-booster showed significantly lower (95) but still 'robust' neutralization than against ancestral B.1 virus (107). Messali 2021 https://doi.org/10.1002/jmv.27247 doi:10.1002/jmv.27247 pmid:34329486 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22597,22597,22599,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23604,23604,24410 T95I,R346K,R346K,R346K,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D950N YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 12.4x reduction of NT50 value B.1.621 (Mu) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. [This is a greater reduction than Beta @ 8.2x] Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22679,22679,23039,23039,23040,24465,24466,24466,24468,24469,23521,23521,23522,23524,23524,23525,23525,24130,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21641,24421,24421,24422,24423,24424,24424,24424,23060,23061,23062,23062,23063,23063,22879,22879,22881,22882,22882,22882,23595,23596,23596,23598,23599,23853,23854,23854,23071,23071,23074,23074,23075,23075,23202,23944,23944,23946,23947,23948,23948,22992,22995,23048,22810,22810,22811,22812,22813,22813,22813,22673,22576,22577,22578,23604,23604,22686,23053,23053,23054,23054,23055,23055,22894,22896,22898,22992,23009,23010,23012,23013,24503,23399,23401,23401,23402,23403,23403 T95I,S373P,S373P,Q493R,Q493R,Q493R,N969K,N969K,N969K,N969K,N969K,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A27S,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,N440K,N440K,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,S371L,G339D,G339D,G339D,P681H,P681H,S375F,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,G446S,G446S,G446S,S477N,E484A,E484A,E484A,E484A,L981F,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Leu981Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 1.5x-fold lower (95% CI: 0.05x-0.07x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22679,22679,23039,23039,23040,24465,24466,24466,24468,24469,23521,23521,23522,23524,23524,23525,23525,24130,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,21641,24421,24421,24422,24423,24424,24424,24424,23060,23061,23062,23062,23063,23063,22879,22879,22881,22882,22882,22882,23595,23596,23596,23598,23599,23853,23854,23854,23071,23071,23074,23074,23075,23075,23202,23944,23944,23946,23947,23948,23948,22992,22995,23048,22810,22810,22811,22812,22813,22813,22813,22673,22576,22577,22578,23604,23604,22686,23053,23053,23054,23054,23055,23055,22894,22896,22898,22992,23009,23010,23012,23013,24503,23399,23401,23401,23402,23403,23403 T95I,S373P,S373P,Q493R,Q493R,Q493R,N969K,N969K,N969K,N969K,N969K,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,N856K,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,A27S,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,Q954H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,N440K,N440K,N440K,N440K,N440K,N440K,N679K,N679K,N679K,N679K,N679K,N764K,N764K,N764K,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,T547K,D796Y,D796Y,D796Y,D796Y,D796Y,D796Y,T478K,T478K,G496S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,S371L,G339D,G339D,G339D,P681H,P681H,S375F,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,G446S,G446S,G446S,S477N,E484A,E484A,E484A,E484A,L981F,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.Asn969Lys,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Asn856Lys,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Ala27Ser,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Gln954His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn679Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Asn764Lys,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Thr547Lys,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Asp796Tyr,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Gly496Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Ser371Leu,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Leu981Phe,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 22 Pfizer/BNT162b2-vaccinated sera (ages 26-74, median 65) collected 1 month after dose 3, XD (from ) were 4.4-fold lower (95% CI: 4.3x-4.7x) than against 208-428 972-1834 4.3-4.7 US-WA1/2020 usiong an infectious cDNA clone of mNG USA-WA1/2020. Kurhade 2022 https://doi.org/10.1101/2022.06.05.494889 doi:10.1101/2022.06.05.494889 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 T95I,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this lineage defining mutation combination from B.1.617.3 conferred a ~11.8x drop in neutralization (NT50) [suggesting role for T19R and T95I in half the sera]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 T95I,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this lineage defining mutation combination from B.1.617.3 increased syncytium formation ~2.3x. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 T95I,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this lineage defining mutation combination from B.1.617.3 conferred a ~4.5x infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,23011,23012,23271,23399,23401,23401,23402,23403,23403,23604,23604,23948 T95I,E484K,E484K,A570D,D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H,D796H YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Asp796His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 51yo female with no severe COVID-19 risk factors tested positive 19 days after second dose of mRNA-1273 (Moderna) vaccine. Presented with sore throat, congestion, and headache developed; the next day she lost her sense of smell. Symptoms resolved over a one week period. Serum obtained 4 days after symptom onset was tested for neutralization against wild-type virus, the E484K mutant, and the B.1.526 variant. It was equally effective against each. These data suggest that the antibody response recognized these variants but was nonetheless insufficient to prevent a breakthrough infection. The virus detected matched neither B.1.1.7 nor B.1.526 VOC strains in wide circulation in New York at the time of infection, though shared some mutations. Hacisuleyman 2021 https://doi.org/10.1056/NEJMoa2105000 doi:10.1056/NEJMoa2105000 pmid:33882219 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,23399,23401,23401,23402,23403,23403 T95I,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21846,23399,23401,23401,23402,23403,23403 T95I,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21855 S98F NC_045512.2(GU280_gp02):g.293C>T YP_009724390.1:p.Ser98Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly enhanced the transduction rate in raccoon dog (Nyctereutes procyonoides) kidney (62.4%) and Rickett’s big-footed bat (Myotis pilosus) kidney (45.0%) cell cultures compared to epithelial-like human Huh-7 cells (38.9%). Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21929 A123S NC_045512.2(GU280_gp02):g.367G>T YP_009724390.1:p.Ala123Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected in passage with mAb COV2-2489 during alanine mutagenesis antibody mapping experiment. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 pmid:33501445 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21969 C136Y NC_045512.2(GU280_gp02):g.407G>A YP_009724390.1:p.Cys136Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21969 C136Y NC_045512.2(GU280_gp02):g.407G>A YP_009724390.1:p.Cys136Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massively decreases N terminal domain antigen recognition by supersite i mAbs S2L28, S2M28, S2X28, S2X333, 4A8. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events These variants dominate in mink infections in North America, sometime supplemented with F486L. The Y453F variant found in other jurisdictions in mink infections is notably absent in North America. 2021 https://doi.org/10.1101/2021.03.18.21253734v3 doi:10.1101/2021.03.18.21253734v3 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. [PG: This mutation is adjacent to a well known deletion, which may confound the significance of this variant] Lucaci 2021 https://observablehq.com/@aglucaci/sc2-omicron Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected twice in passage with mAb COV2-2489. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 pmid:33501445 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~3.5x cleavage of S2 relative to WA1 (D614G) wildtype by Kappa (B.1.617.1) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~4.5x for closely related Delta B.1.617.2 also with P681R at the cleavage site). Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.5x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Inferring from two B.1.617.1 variants tested, estimate baseline 3.3x reduction in ID50 relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.617.1) showed a 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Average 2x neutralization efficiency decrease against sera from 26 Phase II trial Covaxin (BBV152) vaccine recipents. Very similar to B.1.1.7 (~2x) in the same study, and the neutralization from 17 sera of natural infections across B1 lineages. Yadav 2021 https://doi.org/10.1101/2021.04.23.441101 doi:10.1101/2021.04.23.441101 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Relative to B.1, Kappa (B.1.617.1) shows 5.71x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1, Kappa (B.1.617.1) shows mean 1.97x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.617.1) showed a 1.79x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.1) showed a 1.12x increase in binding (KD) relative to D614G, but described as 'not significant'. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775,21846,24863 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H,T95I,H1101D YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.His1101Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Kappa (B.1.617.1) has an IC50 fold change of 80.2x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775,21846,24863 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H,T95I,H1101D YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.His1101Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Kappa (B.1.617.1) has an IC50 fold change of 2.3x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775,21846,24863 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H,T95I,H1101D YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.His1101Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Kappa (B.1.617.1) has an IC50 fold change of 0.68x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775,21846,24863 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H,T95I,H1101D YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.His1101Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Kappa (B.1.617.1) has an IC50 fold change of 0.13x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775,24863 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H,H1101D YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.His1101Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.617.1-v1 ('Kappa') reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24775,24863 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,Q1071H,H1101D YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Gln1071His,YP_009724390.1:p.His1101Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cluster of B.1.617[.1] infections related to travel from India to USA, one patient with mild symptoms had received their second dose of Pfizer vaccine more than two weeks before the infection [i.e. vaccine breakthrough]. Verghese 2021 https://doi.org/10.1128/JCM.00741-21 doi:10.1128/JCM.00741-21 pmid:33952596 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22022,22915,22915,22916,22916,22917,22917,23599,23599,23604,23604,23399,23401,23401,23402,23403,23403,23873,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,E154K,L452R,L452R,L452R,L452R,L452R,L452R,P681R,P681R,P681R,P681R,D614G,D614G,D614G,D614G,D614G,D614G,A771S,D950N YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu154Lys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala771Ser,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4.5x cleavage of S2 relative to WA1 (D614G) wildtype by Delta (B.1.617.2) variant as measured by mass spectrometry of Vero-TMPRSS culture (compare to ~3.5x for closely related Kappa B.1.617.1 also with P681R at the cleavage site). Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against B.1.617.1-v1 ('Kappa') reduced 3.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. [Mutation list in publication appears to contain a typo with R158del instead of R158G] Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Mean 2.6x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from adult BNT162b2 vaccinees (28-47yo) collected ~1m post booster. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mean 4.0x reduction of NT50 value B.1.617.2 (Delta) relative to wild type in 8 sera from older convalescent patients (52-92yo) collected 1-3m post symptom onset. Uriu 2021 https://doi.org/10.1101/2021.09.06.459005 doi:10.1101/2021.09.06.459005 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Modelling the Delta variant in primary human airway epithelial (HAE) cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increased 11x relative to wild type (15.3 vs 1.4). [del ~157 truncated due to ambiguity] Furthermore the RNA ratio of Delta versus Alpha-spike/Delta-backbone continuously increased from 2.8 on day 1 to 9.8 on day 5 post infection in a coinfection model in HAEs, suggesting the spike gene drives the improved replication of Delta variant. Liu 2021 https://doi.org/10.1101/2021.08.12.456173v3 doi:10.1101/2021.08.12.456173v3 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.10x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.020x fold change in IC50 in B.1.617.2 Delta Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,24410 G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,D950N YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In primary human airway epithelial cultures, S1 to full length Spike ratio (measuring Spike furin cleavage processivity) increase 1.9x relative to wild type (2.7 vs 1.4). This is the Delta variant with the P681R furin cleavage site mutation absent. [del ~157 truncated due to ambiguity] Liu 2021 https://doi.org/10.1101/2021.08.12.456173v3 doi:10.1101/2021.08.12.456173v3 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21974 D138Y NC_045512.2(GU280_gp02):g.412G>T YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.43 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21974,23224,23399,23401,23401,23402,23403,23403 D138H,E554D,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp138His,YP_009724390.1:p.Glu554Asp,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Studying 94 COVID-19 extended infection cases with genomics April 1 to October 17, 2020, one case developed 23 mutations in a 19 day period, including this combination in Spike. Landis 2021 https://doi.org/10.1101/2021.05.08.21256775 doi:10.1101/2021.05.08.21256775 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21977 P139S NC_045512.2(GU280_gp02):g.415C>T YP_009724390.1:p.Pro139Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2(GU280_gp02):g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2L28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2(GU280_gp02):g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected once in passage with mAb COV2-2676. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 pmid:33501445 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21981 F140S NC_045512.2(GU280_gp02):g.419T>C YP_009724390.1:p.Phe140Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990 Y145del,Y145del NC_045512.2(GU280_gp02):g.432_434del,NC_045512.2(GU280_gp02):g.432_434del YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient. McCarthy 2021 https://doi.org/10.1126/science.abf6950 doi:10.1126/science.abf6950 pmid:33536258 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990 Y145del,Y145del NC_045512.2(GU280_gp02):g.432_434del,NC_045512.2(GU280_gp02):g.432_434del YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21987,21990,21993,21995,23011,23012,23399,23401,23401,23402,23403,23403 Y145del,Y145del,H146del,H146del,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Tyr145del,YP_009724390.1:p.Tyr145del,YP_009724390.1:p.His146del,YP_009724390.1:p.His146del,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Normalized for particle number, on ACE2.293T cells showed that the B.1.618 spike protein was about as infective as D614G wild type. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21993,21995 H146del,H146del NC_045512.2(GU280_gp02):g.436_438del,NC_045512.2(GU280_gp02):g.436_438del YP_009724390.1:p.His146del,YP_009724390.1:p.His146del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient. McCarthy 2021 https://doi.org/10.1126/science.abf6950 doi:10.1126/science.abf6950 pmid:33536258 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21997,21997,21998,21999,22000,22000,22001 K147E,K147E,K147E,K147E,K147E,K147E,K147E YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2X28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21997,21997,21998,21999,22000,22000,22001 K147E,K147E,K147E,K147E,K147E,K147E,K147E YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu,YP_009724390.1:p.Lys147Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 21998,21998 H146Y,H146Y NC_045512.2(GU280_gp02):g.436C>T, YP_009724390.1:p.His146Tyr,YP_009724390.1:p.His146Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in 4A8 monoclonal antibody EC50 (i.e. ablated recognition), but much milder effect on mAbs within antigenic supersite 'i' McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22001 K147Q NC_045512.2(GU280_gp02):g.439A>C YP_009724390.1:p.Lys147Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22002 K147T NC_045512.2(GU280_gp02):g.440A>C YP_009724390.1:p.Lys147Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massively decreases N terminal domain antigen recognition by supersite i mAbs S2M28, S2X28, S2X333, 4A8 (but not S2L28). McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22002 K147T NC_045512.2(GU280_gp02):g.440A>C YP_009724390.1:p.Lys147Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAbs S2M28, S2X333 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22003,22003 K147N,K147N NC_045512.2(GU280_gp02):g.441A>C,NC_045512.2(GU280_gp02):g.441A>T YP_009724390.1:p.Lys147Asn,YP_009724390.1:p.Lys147Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22005 N148S NC_045512.2(GU280_gp02):g.443A>G YP_009724390.1:p.Asn148Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong positive selection (up to 72% of supernatant sequences) under six rounds of COV47 convalescent plasma passage Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22010 K150E NC_045512.2(GU280_gp02):g.448A>G YP_009724390.1:p.Lys150Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22010 K150E NC_045512.2(GU280_gp02):g.448A>G YP_009724390.1:p.Lys150Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong positive selection (up to 40% of supernatant sequences) under three rounds of COV47 convalescent plasma passage Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22011 K150R NC_045512.2(GU280_gp02):g.449A>G YP_009724390.1:p.Lys150Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 18% of supernatant sequences) under two rounds of COV47 convalescent plasma passage Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22011 K150T NC_045512.2(GU280_gp02):g.449A>C YP_009724390.1:p.Lys150Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 22% of supernatant sequences) after COV47 convalescent plasma assay Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22016,22016,22016 W152R,W152R,W152R ,NC_045512.2(GU280_gp02):g.454T>C,NC_045512.2(GU280_gp02):g.454T>A YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 12 convalescent sera more than 2 weeks and less than 2 months post infection, this NTD mutation causes a ~3.5x drop in neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22016,22016,22016 W152R,W152R,W152R ,NC_045512.2(GU280_gp02):g.454T>C,NC_045512.2(GU280_gp02):g.454T>A YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg,YP_009724390.1:p.Trp152Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For NTD-binding neutralizing antibody ADI-56479 this mutation causes a 1000x drop in neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22016,22017,23011,23012,23399,23401,23401,23402,23403,23403,23868 W152L,W152L,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,G769V YP_009724390.1:p.Trp152Leu,YP_009724390.1:p.Trp152Leu,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gly769Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The estimated vaccine effectiveness against R.1 strain SARS-CoV-2 infection among residents in a Kentucky skilled nursing facility was 66.2% (95% CI = 40.5%–80.8%) and among health care workers was 75.9% (95% CI = 32.5%–91.4%) in the cohort of only those 14d+ post-vaccination Pfizer booster dose. VE against symptomatic COVID-19 was 86.5% (95% CI = 65.6%–94.7%) among residents and 87.1% (95% CI = 46.4%–96.9%) among HCP. VE against hospitalization was 94.4% (95% CI = 73.9%–98.8%) among residents; no HCP were hospitalized. Three residents died, two of whom were unvaccinated (VE = 94.4%; 95% CI = 44.6%–99.4%). Cavanaugh 2021 https://doi.org/10.15585/mmwr.mm7017e2 doi:10.15585/mmwr.mm7017e2 pmid:33914720 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22018 W152C NC_045512.2(GU280_gp02):g.456G>T YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Pseudoviruses carrying the W152C mutation demonstrated small increases in cell entry compared to D614G alone in 293T cells and human airway organoids. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 pmid:33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22018 W152C NC_045512.2(GU280_gp02):g.456G>T YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects The W152C mutation reduced recognition of six NTD neutralizing mAbs, including a complete loss of binding for two of them, with a complementary pattern to that observed for S13I (also found in lineage B.1.427/B.1.429) out of 11 neutralizing mAbs evaluated. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22022 E154K NC_045512.2(GU280_gp02):g.460G>A YP_009724390.1:p.Glu154Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034 R158G,R158G NC_045512.2(GU280_gp02):g.467_472del,NC_045512.2(GU280_gp02):g.472A>G YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Plasma neutralizing activity was also assessed against SARS-CoV-2 Delta, Omicron BA.1, BA.2 and BA.4/5 variants using viruses pseudotyped with appropriate variant spikeproteins. Delta breakthrough infection resulted in 15-fold increased neutralizing titers. Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity L27, V34 and E90 mutation resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 507 pM for binding to the Delta B.1.617.2. Values were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Plasma neutralizing activity in 49 participants was measured using HIV-1 pseudotyped with the 100 WT SARS-CoV-2 spike protein. Delta breakthrough infection resulted in 11-fold increased geometric mean half-maximal neutralizing titer (NT50). Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Delta neutralizing antibodies is 0.872x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Paradigm’s ACE-2 variant LVE/STR chimera neutralizes Delta Variant B.1.617.2 RBD or w.t. SARS-CoV-2 RBD with nearly equal potency determined using Surrogate Viral Neutralization Tests. Uhal B 2022 https://doi.org/10.1101/2022.06.23.497326 doi:10.1101/2022.06.23.497326 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Delta neutralizing antibodies is 0.952x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In the UK, of 43338 COVID-19-positive patients, 8682 had the Delta variant (median age 31 years [IQR 17–43]) and 196 were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2.26 [95% CI 1.32–3.89] relative to Alpha cases). Being admitted to hospital or attending emergency care within 14 days for Delta cases had an adjusted HR 1.45 [95% CI 1.08–1.95] relative to Alpha. Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients were similar: 1.94 [95% CI 0.47–8.05] for hospitalization and 1.58 [0.69–3.61]) for hospital admission or emergency care attendance. Twohig 2021 https://doi.org/10.1016/S1473-3099(21 doi:10.1016/S1473-3099(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy During December 14, 2020–August 14, 2021, frontline worker without previous documented SARS-CoV-2 infection were monitored regularly. Of 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. This trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Fowlkes 2021 https://doi.org/10.15585/mmwr.mm7034e4 doi:10.15585/mmwr.mm7034e4 pmid:34437521 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Case 62541 cluster in Singapore included a fully vaccinated nurse 2 months post-vaccine [likely Pfizer based on dates and supply], and a doctor of unknown vaccine status. This cluster was caused by a B.1.617.2 virus [via crossreference to Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.64x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.89x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy https://www.moh.gov.sg/news-highlights/details/3-new-cases-of-locally-transmitted-covid-19-infection-28apr2021-update False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy 136,160 reports from 14,997 nursing care facilities were broken into pre-Delta (Mar 1-May 9, 2021), intermediate (May 10-Jun 20, 2021) and Delta (Jun 21-Aug 1, 2021). Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%. Nanduri 2021 https://doi.org/10.15585/mmwr.mm7034e3 doi:10.15585/mmwr.mm7034e3 pmid:34437519 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a matched test-negative, case- control study design in Qatar, BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. The lower VE in Qatar relative to those reported in some other jurisdictions such as the UK and Canada (75%+) may reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Risk perception and behaviour amongst vaccinated individuals opver time may also play a role. Tang 2021 https://doi.org/10.1101/2021.08.11.21261885 doi:10.1101/2021.08.11.21261885 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Denmark, for the period Jan 1 to Jun 27, 2021, Delta variant was associated with increased an risk ratio of 2.83 [95% CI 2.02–3.98] for hospitalization. Bager 2021 https://doi.org/10.1016/S1473-3099(21 doi:10.1016/S1473-3099(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Of 218 individuals with B.1.617.2 infection in Singapore, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). Chia 2021 https://doi.org/10.1101/2021.07.28.21261295 doi:10.1101/2021.07.28.21261295 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy The incidence rate of Covid-19 during the Delta-dominant period (Jul-Aug 2021) was lower for late vaccinated (49.0/1000 person-years) [formerly placebo] versus early vaccinated (77.1/1000 person-years) participants in the Moderna mRNA-1273 Phase 3 trials, representing a 36.4% VE reduction (95% CI 17.1%-51.5%). There were fewer severe Covid-19 cases in the late group (6; 6.2/1000 person-years) than early (13; 3.3/1000 person-years), representing a 46.0% reduction (95% CI −52.4%-83.2%). Three Covid-19 related hospitalizations occurred with two resulting deaths in the early group. Baden 2021 https://doi.org/10.1101/2021.09.17.21263624 doi:10.1101/2021.09.17.21263624 pmid:34611666 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 2.3x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) [exact set of variants used is not listed in the manuscript] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Delta Molnupiravir (MK-4482) had ~4x fold drop. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 pmid:35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Using a test-negative design using Ontario data between Dec 14, 2020 and May 30, 2021, 421,073 symptomatic community-dwelling individuals were tested. Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Delta-positive cases were biased towards young male residents of the Peel region. Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) outcome hazard ratio In Ontario between Feb 7 and Jun 27, 2021, increased risk with the Delta variant was 108% (95% CI 78%–140%) for hospitalization, 235% (95% CI 160%–331%) for ICU admission and 133% (95% CI 54%–231%) for death. 2021 https://doi.org/10.1503/cmaj.211248 doi:10.1503/cmaj.211248 pmid:34610919 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Vaccination of health care workers in Delhi was started in early 2021, with the ChdOx-1 (Astra Zeneca) vaccine. Surveillance has suggested B.1.1.7 dominance in the Delhi area during early 2021, with growth of B.1.617 since March 2021. During the wave of infections during March and April an outbreak of SARS-CoV-2 was confirmed in 33 vaccinated staff members at a single tertiary centre (age 27-77 years). Sequencing revealed that 16/33 were B.1.617.2, with a range of other B lineage viruses including B.1.1.7 for the rest except one A lineage case. Importantly no severe cases were documented in this event. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) with the delta variant was (30.7%; 95% confidence interval [CI], 25.2 to 35.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Lopez Bernal 2021 https://doi.org/10.1056/NEJMoa2108891 doi:10.1056/NEJMoa2108891 pmid:34289274 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.617.2 aka Delta) showed a 1.92x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617.2 aka Delta) showed a 2.34x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred and represents minimal set agreed upon commonly] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In Minnesota in July 2020 (when Delta variant prevalence was >70%), the effectiveness against infection for mRNA-1273 was estimated at 76% (95% CI: 58-87%) using age, sex, race, PCR testing and vaccination date matched cohorts of unvaccinated, Pfizer and Moderna vaccinees. An even more pronounced reduction in effectiveness was observed for BNT162b2 of 42% (95% CI: 13-62%). mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). [variant list included is ancestral Delta, as this was an observational study no variant list was given] Puranik 2021 https://doi.org/10.1101/2021.08.06.21261707 doi:10.1101/2021.08.06.21261707 pmid:34401884 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 2027 test-positive cases were Delta. Two dose vaccine efficacy against Delta decreased from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 47D10. Delta (B.1.617.2) has an IC50 fold change of 46.5x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab35B5-47D10. Delta (B.1.617.2) has an IC50 fold change of 0.57x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs Bi-Nab47D10-35B5. Delta (B.1.617.2) has an IC50 fold change of 0.15x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Neutralization of the bsAbs 35B5. Delta (B.1.617.2) has an IC50 fold change of 0.87x. Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22028,22034,22915,22915,22916,22916,22917,22917,22992,22995,23399,23401,23401,23402,23403,23403,23599,23599,23604,23604,24410,21971,21972,21972,21974,21976,21976,21979,21981,21982,21984,21984,21985,21985,21986,21987,21987 R158G,R158G,L452R,L452R,L452R,L452R,L452R,L452R,T478K,T478K,D614G,D614G,D614G,D614G,D614G,D614G,P681R,P681R,P681R,P681R,D950N,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D,G142D YP_009724390.1:p.Glu156_Arg158delinsGly,YP_009724390.1:p.Arg158Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp950Asn,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp,YP_009724390.1:p.Gly142Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects BnAb 002-S21F2 IC50 on the Delta (B.1.617.2) variant is 0.6x fold the wildtype. Kumar 2022 https://doi.org/10.1101/2022.05.13.491770 doi:10.1101/2022.05.13.491770 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22031,22033,23011,23012,23599,23599,23604,23604 F157L,F157L,E484K,E484K,P681R,P681R,P681R,P681R YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against A.23.1-v2 reduced 2.3x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22031,22033,23599,23599,23604,23604 F157L,F157L,P681R,P681R,P681R,P681R YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Phe157Leu,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralization efficiency (ID50) against A.23.1-v1 reduced 1.1x relative to D614G wildtype using pseudotyped VSV assay on 8 Moderna vaccinee sera one week post-booster. Choi 2021 https://doi.org/10.1101/2021.06.28.449914 doi:10.1101/2021.06.28.449914 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22036 R158S NC_045512.2(GU280_gp02):g.474A>T YP_009724390.1:p.Arg158Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Selected three times in passage with mAb COV2-2489. Suryadevara 2021 https://doi.org/10.1101/2021.01.19.427324 doi:10.1101/2021.01.19.427324 pmid:33501445 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2(GU280_gp02):g.531G>C,NC_045512.2(GU280_gp02):g.531G>T,NC_045512.2(GU280_gp02):g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2(GU280_gp02):g.531G>C,NC_045512.2(GU280_gp02):g.531G>T,NC_045512.2(GU280_gp02):g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*16:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2(GU280_gp02):g.531G>C,NC_045512.2(GU280_gp02):g.531G>T,NC_045512.2(GU280_gp02):g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*07:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2(GU280_gp02):g.531G>C,NC_045512.2(GU280_gp02):g.531G>T,NC_045512.2(GU280_gp02):g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type C*07:02. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2(GU280_gp02):g.531G>C,NC_045512.2(GU280_gp02):g.531G>T,NC_045512.2(GU280_gp02):g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:03. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2(GU280_gp02):g.531G>C,NC_045512.2(GU280_gp02):g.531G>T,NC_045512.2(GU280_gp02):g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*05:02. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2(GU280_gp02):g.531G>C,NC_045512.2(GU280_gp02):g.531G>T,NC_045512.2(GU280_gp02):g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:02. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2(GU280_gp02):g.531G>C,NC_045512.2(GU280_gp02):g.531G>T,NC_045512.2(GU280_gp02):g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DQB1*02:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22093,22093,22093 M177I,M177I,M177I NC_045512.2(GU280_gp02):g.531G>C,NC_045512.2(GU280_gp02):g.531G>T,NC_045512.2(GU280_gp02):g.531G>A YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile,YP_009724390.1:p.Met177Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DPB1*04:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22107,22111 Q183H,Q183H NC_045512.2(GU280_gp02):g.549G>T,NC_045512.2(GU280_gp02):g.549G>T YP_009724390.1:p.Gln183His,YP_009724390.1:p.Gln183His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 pmid:33176080 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22132 R190S NC_045512.2(GU280_gp02):g.570G>T YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.69 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22188,23399,23401,23401,23402,23403,23403 I210del,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Ile210del,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection A 42yo Iranian male was reinfected with B.1.36 lineage virus 128 days after infection with genetically distinct B.1.36 virus, with negative PCR tests in between. In the first instance patient presented with cough, headache, severe diarrhea. In the second instance symptoms were more severe: body pain, shortness of breath, headache and anosmia. Anti-SARS-CoV-2 IgG and IgM tests were negative after both episodes. [Non-seroconversion may be associated with elevated risk of re-infection] [I210del is a homoplasy that has appeared in several disparate parts of the global phylogenetic tree, including A and B lineages, primarily in LMICs] Salehi-Vaziri 2021 https://doi.org/10.1016/j.virusres.2021.198421 doi:10.1016/j.virusres.2021.198421 pmid:33836204 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2(GU280_gp02):g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*13:02. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 pmid:34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2(GU280_gp02):g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:01. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 pmid:34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2(GU280_gp02):g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.98 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2(GU280_gp02):g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2(GU280_gp02):g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA type DRB1*03:02. Riou 2021 https://doi.org/10.1126/scitranslmed.abj6824 doi:10.1126/scitranslmed.abj6824 pmid:34931886 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22206 D215G NC_045512.2(GU280_gp02):g.644A>G YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22227 A222V NC_045512.2(GU280_gp02):g.665C>T YP_009724390.1:p.Ala222Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not associated with significant reduction of EC50 (recognition) in any antigenic supersite 'i' monoclonal antibodies. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22227,23399,23401,23401,23402,23403,23403 A222V,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) humoral response durability 27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3), i.e. with a 9 month interval. Both cases were mild. No significant differences in the neutralizing capacity of the two lineages were observed in 4 sera taken (1 pre-reinfection, three post-reinfection). Neutralizing antibody titres (IC50) before and immediately after re-infection were <300 against both strains, and jumped >7x upon re-infection. Viral titres were also higher in the second case. Second case also includes N:p.A220V Brehm 2021 https://doi.org/10.3390/v13040661 doi:10.3390/v13040661 pmid:33921216 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22227,23399,23401,23401,23402,23403,23403 A222V,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Ala222Val,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 27yo female nurse reinfected in December 2020 (B.1.177) after initial infection in March 2020 (B.3). Both cases were mild. Second case also includes N:p.A220V Brehm 2021 https://doi.org/10.3390/v13040661 doi:10.3390/v13040661 pmid:33921216 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22293 L244S NC_045512.2(GU280_gp02):g.731T>C YP_009724390.1:p.Leu244Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22294,22302 L244F,Y248del NC_045512.2(GU280_gp02):g.732A>C,NC_045512.2(GU280_gp02):g.743_745del YP_009724390.1:p.Leu244Phe,YP_009724390.1:p.Tyr248del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Virus evolution data in 9 immunocomprised patients with long active COVID-19 infections was gathered, showing sequence deletion hotspots. This variant was present in 1 patient. McCarthy 2021 https://doi.org/10.1126/science.abf6950 doi:10.1126/science.abf6950 pmid:33536258 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22301,22303 S247R,S247R NC_045512.2(GU280_gp02):g.739A>C,NC_045512.2(GU280_gp02):g.741T>G YP_009724390.1:p.Ser247Arg,YP_009724390.1:p.Ser247Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22304 Y248H NC_045512.2(GU280_gp02):g.742T>C YP_009724390.1:p.Tyr248His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22314 P251L NC_045512.2(GU280_gp02):g.752C>T YP_009724390.1:p.Pro251Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2X28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317 G252D NC_045512.2(GU280_gp02):g.755G>A YP_009724390.1:p.Gly252Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317,22319,22320 D253G,D253G,D253G NC_045512.2(GU280_gp02):g.758A>G,NC_045512.2(GU280_gp02):g.758A>G,NC_045512.2(GU280_gp02):g.758A>G YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22317,22319,22320 D253G,D253G,D253G NC_045512.2(GU280_gp02):g.758A>G,NC_045512.2(GU280_gp02):g.758A>G,NC_045512.2(GU280_gp02):g.758A>G YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite 'i', but no effect on other mAbs within that supersite McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22319 D253Y NC_045512.2(GU280_gp02):g.757G>T YP_009724390.1:p.Asp253Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in S2L28 monoclonal antibody EC50 (i.e. ablated recognition), within antigenic supersite 'i', but no effect on other mAbs within that supersite McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22323 S254Y NC_045512.2(GU280_gp02):g.761C>A YP_009724390.1:p.Ser254Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22323 S254F NC_045512.2(GU280_gp02):g.761C>T YP_009724390.1:p.Ser254Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not associated with significant reduction of EC50 (recognition) in any antigenic supersite 'i' monoclonal antibodies. McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22326 S255F NC_045512.2(GU280_gp02):g.764C>T YP_009724390.1:p.Ser255Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22328,22329,22331 G257S,G257S,G257S NC_045512.2(GU280_gp02):g.769G>A,NC_045512.2(GU280_gp02):g.769G>A,NC_045512.2(GU280_gp02):g.769G>A YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser,YP_009724390.1:p.Gly257Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334 W258R NC_045512.2(GU280_gp02):g.772T>C YP_009724390.1:p.Trp258Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334 W258R NC_045512.2(GU280_gp02):g.772T>C YP_009724390.1:p.Trp258Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against Spike N terminal domain antigenic supersite i mAb S2L28 McCallum 2021 https://doi.org/10.1101/2021.01.14.426475 doi:10.1101/2021.01.14.426475 pmid:33469588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22334,22879,22879,22881,22882,22882,22882,22904,22910,23011,23012 W258R,N440K,N440K,N440K,N440K,N440K,N440K,N450D,N450D,E484K,E484K YP_009724390.1:p.Trp258Arg,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22338 T259K NC_045512.2(GU280_gp02):g.776C>A YP_009724390.1:p.Thr259Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Six minks were intranasally infected with WA1 isolate, three developed this mutation during infection. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22340 A260T NC_045512.2(GU280_gp02):g.778G>A YP_009724390.1:p.Ala260Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22341 A260V NC_045512.2(GU280_gp02):g.779C>T YP_009724390.1:p.Ala260Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22344 G261D NC_045512.2(GU280_gp02):g.782G>A YP_009724390.1:p.Gly261Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Multiple mink but no humans on one farm in Denmark, potential adaptation. Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 pmid:33172935 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22377,22377 P272L,P272L ,NC_045512.2(GU280_gp02):g.815C>T YP_009724390.1:p.Pro272Leu,YP_009724390.1:p.Pro272Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*02:01. Dolton 2021 https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf doi:10.1101/2021.06.21.21259010v2.full.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22377,22377 P272L,P272L ,NC_045512.2(GU280_gp02):g.815C>T YP_009724390.1:p.Pro272Leu,YP_009724390.1:p.Pro272Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*08:01. Dolton 2021 https://doi.org/10.1101/2021.06.21.21259010v2.full.pdf doi:10.1101/2021.06.21.21259010v2.full.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22573,22574,22576,22577 G339H,G339H,G339H,G339H YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.15 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22573,22574,22576,22577,22596,22597,22597,22599,22599,22660,22660,22661,22663,22663,22664,22664,22671,22672,22672,22673,22674,22679,22679,22686,22771,22775,22775,22783,22783,22784,22785,22786,22786,22810,22810,22811,22812,22813,22813,22813,22879,22879,22881,22882,22882,22882,22895,22894,22896,22898,22938,22939,22939,22942,22942,22942,22992,23009,23010,23012,23013,23017,23018,23027,23029,23029,23030,23031,23031,23053,23053,23054,23054,23055,23055,22992,22995,23060,23061,23062,23062,23063,23063,23071,23071,23074,23074,23075,23075 G339H,G339H,G339H,G339H,R346T,R346T,R346T,R346T,R346T,L368I,L368I,L368I,L368I,L368I,L368I,L368I,S371F,S371F,S371F,S371F,S371F,S373P,S373P,S375F,D405N,D405N,D405N,R408S,R408S,R408S,R408S,R408S,R408S,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N440K,N440K,N440K,N440K,N440K,N440K,V445P,G446S,G446S,G446S,N460K,N460K,N460K,N460K,N460K,N460K,S477N,E484A,E484A,E484A,E484A,F486P,F486P,F490S,F490S,F490S,F490S,F490S,F490S,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,T478K,T478K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Gly339His,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Leu368Ile,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser371Phe,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser375Phe,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Asp405Asn,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Val445Pro,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Gly446Ser,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The hACE2-binding affinity of XBB.1.5 RBD has a dissociation constant KD of 3.4 nM, where S486P is the distinguishing Spike mutation vs parent XBB.1 RBD with a much weaker KD (19 nM), as measured by surface plasmon resonance (SPR) assays. Yue 2023 https://doi.org/10.1101/2023.01.03.522427 doi:10.1101/2023.01.03.522427 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2(GU280_gp02):g.1016G>A,NC_045512.2(GU280_gp02):g.1016G>A,NC_045512.2(GU280_gp02):g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 1.2x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2(GU280_gp02):g.1016G>A,NC_045512.2(GU280_gp02):g.1016G>A,NC_045512.2(GU280_gp02):g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22576,22577,22578 G339D,G339D,G339D NC_045512.2(GU280_gp02):g.1016G>A,NC_045512.2(GU280_gp02):g.1016G>A,NC_045512.2(GU280_gp02):g.1016G>A YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp,YP_009724390.1:p.Gly339Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.3 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22577 G339N YP_009724390.1:p.Gly339Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.11 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22583 V341I NC_045512.2(GU280_gp02):g.1021G>A YP_009724390.1:p.Val341Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22596,22597,22597,22599,22599 R346T,R346T,R346T,R346T,R346T YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.15 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22596,22597,22597,22599,22599 R346T,R346T,R346T,R346T,R346T YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr,YP_009724390.1:p.Arg346Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22597,22599 R346K,R346K,R346K ,NC_045512.2(GU280_gp02):g.1037G>A,NC_045512.2(GU280_gp02):g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation, which has emerged in some Omicron sequences, has a 0.7x reduction in neutralization activity with Sotrovimab in a VSV model on Vero E6 cells. [Omicron sequences with R346K may very well have a non-additive neutralization rather than 2.7x+0.7x = 3.4x] Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22597,22599 R346K,R346K,R346K ,NC_045512.2(GU280_gp02):g.1037G>A,NC_045512.2(GU280_gp02):g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 53% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22597,22599 R346K,R346K,R346K ,NC_045512.2(GU280_gp02):g.1037G>A,NC_045512.2(GU280_gp02):g.1037G>A YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22597,22599 R346I,R346I NC_045512.2(GU280_gp02):g.1037G>T,NC_045512.2(GU280_gp02):g.1037G>T YP_009724390.1:p.Arg346Ile,YP_009724390.1:p.Arg346Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Provides ~80% escape from mAb COV2-2130, even though its appearance in culture is formed without selective mAb pressure. Dong 2021 https://doi.org/10.1101/2021.01.27.428529 doi:10.1101/2021.01.27.428529 pmid:33532768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22598 R346E YP_009724390.1:p.Arg346Glu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.08 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2(GU280_gp02):g.1038A>T,NC_045512.2(GU280_gp02):g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Positive selection (up to 30% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, overall 70% switch away from R346 to S, K or M Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2(GU280_gp02):g.1038A>T,NC_045512.2(GU280_gp02):g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 pmid:33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22600,22600 R346S,R346S NC_045512.2(GU280_gp02):g.1038A>T,NC_045512.2(GU280_gp02):g.1038A>C YP_009724390.1:p.Arg346Ser,YP_009724390.1:p.Arg346Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 2/3 antibody C603. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22622 N354D NC_045512.2(GU280_gp02):g.1060A>G YP_009724390.1:p.Asn354Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.13 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22623 N354S YP_009724390.1:p.Asn354Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.17 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22624 N354K NC_045512.2(GU280_gp02):g.1062C>A YP_009724390.1:p.Asn354Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22627,22627,22629 K356T,K356T,K356T ,NC_045512.2(GU280_gp02):g.1067A>C,NC_045512.2(GU280_gp02):g.1067A>C YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr,YP_009724390.1:p.Lys356Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.14 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22629 K356R NC_045512.2(GU280_gp02):g.1067A>G YP_009724390.1:p.Lys356Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22632 R357K NC_045512.2(GU280_gp02):g.1070G>A YP_009724390.1:p.Arg357Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.18 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2(GU280_gp02):g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected variants in an in vitro evolution experiment for ACE2 binding, described as 'stabilizing' since it nicely fitsinside the hydrophobic pocket formed in the RBD domain. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2(GU280_gp02):g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22634 I358F NC_045512.2(GU280_gp02):g.1072A>T YP_009724390.1:p.Ile358Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.72 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22661 V367I NC_045512.2(GU280_gp02):g.1099G>A YP_009724390.1:p.Val367Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22679,22679 S373P,S373P NC_045512.2(GU280_gp02):g.1117T>C, YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Reduce affinity for mildly cross-reactive CR3022 (2003 pandemic SARS monoclonal antibody cross-reactive to SARS-CoV-2) Long 2020 https://doi.org/10.1128/mBio.02707-20 doi:10.1128/mBio.02707-20 pmid:33127862 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22679,22679,23009,23010,23012,23013 S373P,S373P,E484A,E484A,E484A,E484A YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Ser373Pro,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility On December 7, 2021 the estimate of Omicron effective reproduction rate (Rt) is 3.12 [presumably R0 is higher], compared to 1.12 for the dominant Delta VOC at that time. [shorthand of variant list shraed by all contemporary BA lineage used here] 2021 https://doi.org/10.47326/ocsat.dashboard.2021.1.0 doi:10.47326/ocsat.dashboard.2021.1.0 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22686 S375F NC_045512.2(GU280_gp02):g.1124C>T YP_009724390.1:p.Ser375Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. Lucaci 2021 https://observablehq.com/@aglucaci/sc2-omicron Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22696 K378N NC_045512.2(GU280_gp02):g.1134G>T YP_009724390.1:p.Lys378Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Ranked moderately effective mutant against this position in the RBD for mildly neutralizing COV2-2677 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23401,23402,23403,23403 P384L,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23401,23402,23403,23403 P384L,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22713,23399,23401,23401,23402,23403,23403 P384L,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Pro384Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22745 V395I NC_045512.2(GU280_gp02):g.1183G>A YP_009724390.1:p.Val395Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22766 I402V NC_045512.2(GU280_gp02):g.1204A>G YP_009724390.1:p.Ile402Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22783,22783,22784,22785,22786,22786 R408S,R408S,R408S,R408S,R408S,R408S YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22783,22783,22784,22785,22786,22786,23009,23010,23012,23013,23060,23061,23062,23062,23063,23063 R408S,R408S,R408S,R408S,R408S,R408S,E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Arg408Ser,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a study of 481 vaccinees going from lowest to highest infection rate, 2 doses of CoronaVac and 1 dose of BNT162b2 had the lowest infection rate at 6.3%, then it was 3 doses of BNT162b2 having a infection rate of 16.6%. 2 and 3 doses of CoronaVac had 48.6% and 20.6% infection rate respectively. 2 doses of BNT162b2 has the highest infection rate at 49.2%. Zhou 2022 https://doi.org/10.1101/2022.05.09.491254 doi:10.1101/2022.05.09.491254 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22784 R408G YP_009724390.1:p.Arg408Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.09 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects >20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against IgG1 monoclonal antibody ab1. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 3-fold decrease in affinity compared to wild-type RBD on the cell surface (Kd = 145.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The K417N mutation decreased the affinity ~4 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C682, and to a lesser extent C614 and C660 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 7.5 fold decrease in KD value for antibody binding of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 1.5 fold decrease in KD value of antibody binding of ACE2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 19 convalescent human sera ~1mo post infection, Two-tailed Wilcoxon matched-pairs signed-rank test shows mild resistance P=0.0361. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 36.9 fold decrease in KD value for antibody binding of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~6x binding against this isolated mutation. Estesevimab lost ~100x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotyped virus model ablates binding by RBD-directed mAbs CB6 and 910-30 (targeting the inner side of the RBD). Pseudotyped virus model impairs binding by RBD-directed mAbs 4-20 and REGN10933. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 5 antibodies tested were less potent against K417N by ten-fold or more (class 1 mAbs) Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.86 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 1.1 fold drop in IC50 of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813 K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In Moderna vaccinee sera, 2.7x reduction in neutralization, and 6.4 for the full B.1.351 Spike mutation complement, but despite the observed decreases, titers in human vaccinee sera against the B.1.351 variant remained at clinically significant level of ~1/300. Wu 2021 https://doi.org/10.1101/2021.01.25.427948 doi:10.1101/2021.01.25.427948 pmid:33501442 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape 27% of 44 early pandemic exposure convalescent plasma/sera lose all activity against a RBD triple mutant pseudovirus (RBD mutatants of the 501Y.V2 'South African' lineage), while only 23% retained high titres Wibmer 2021 https://doi.org/10.1101/2021.01.18.427166 doi:10.1101/2021.01.18.427166 pmid:33501446 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load B.1.351 and P.1 samples showed average Ct cycle threshold of 22.2 vs 23 for wildtype (i.e. ~60% higher viral load) comparing 3360 and 22535 samples respectively. Roquebert 2021 https://doi.org/10.1101/2021.03.19.21253971 doi:10.1101/2021.03.19.21253971 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutated version of RBD completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 pmid:33619479 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a significant (0.5 to 20-fold, but average ~2x) decrease in neutralization by vaccine plasma was observed. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of the B.1.351 RBD variants for ACE2 increased by 3.7 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CA1 on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody LyCoV016 (also known as CB6 or JS016) on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 1 (Spike 'up' conformation only, RBD targeting) monoclonal antibody CC12.1 on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody BD23 on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody C119 (also known as CB6 or JS016) on 501Y.V2 ('South African') lineage background Ablates ELISA test binding for class 2 (Spike 'up' or 'down' conformation, RBD targeting) monoclonal antibody P2B-2F6 on 501Y.V2 ('South African') lineage background Wibmer 2021 https://doi.org/10.1101/2021.01.18.427166 doi:10.1101/2021.01.18.427166 pmid:33501446 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against most samples Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from B.1.351. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This combination showed ~3x increase binding to ACE2 vs wild type, about half that of the B.1.1.7 lineage, suggesting that the K417N mutation is slightly detrimental to ACE2 binding, probably as a result of disrupting the salt bridge formed with ACE2 residue D30 Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 1.4-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.351 key variants lentivirus. Compare to 8.8-fold reduction against cultured B.1.351 virus. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 pmid:33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibodies ab8 and IgG1 ab1. Complete loss for the same antibodies was also observed against S1 pseudotyped and full Spike protein trimers with both B.1.351 and P.1 lineage variants, with slight binding signal for P.1 against IgG1 at the highest concentration tested (1uM). Complete loss of neutralization by these two antibodies was also observed. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using Mircoscale Thermopheresis, the B.1.351 variant harboring three mutations, binds ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD (Kd 87.6, vs 402.5 nM). Ramanathan 2021 https://doi.org/10.1101/2021.02.22.432359 doi:10.1101/2021.02.22.432359 pmid:33655251 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y. Laffeber 2021 https://doi.org/10.1101/2021.02.22.432357 doi:10.1101/2021.02.22.432357 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load The 62 B.1.351 (a.k.a. N501Y.V2) variant cases in three Paris hospital labs had a ~2-fold viral load increase (~1 Ct drop in both N and ORF1ab probes) compared to 332 ancestral lineage cases from the same time frame (2020-12-20 to 2021-02-26). Teyssou 2021 https://doi.org/10.1101/2021.03.21.21253498 doi:10.1101/2021.03.21.21253498 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported slight increase in affinity compared to wild-type RBD on the cell surface (Kd = 45.2nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Studying the key covariants in lineage of concern 501Y.V2, observed about 2-fold increase in ACE2 binding vs wildtype, but greatly decreased mAb binding, suggesting evolutionary optimum tension between immune evasion and ACE2 binding affinity as the N501Y variant alone has 10x increase in affinity but no effect on tested mAb binding. Liu 2021 https://doi.org/10.1101/2021.02.16.431305 doi:10.1101/2021.02.16.431305 pmid:33619479 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of ACE2 for this mutation combination was twice as high as for wild type. Having in mind that the affinity of SARS-CoV-2 for ACE2 is only 4-fold higher compared to SARS-CoV-1, this factor of 2 is expected to be biologically significant. Vogel 2021 https://doi.org/10.1101/2021.03.04.433887 doi:10.1101/2021.03.04.433887 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking The entry efficiencies of Spike pseudotyped viruses bearing N501Y Variant 2 (B.1.351) mutant were about 3 to 4.4 times higher than that of the WT pseudovirus when viral input was normalized, suggesting that these spike variants promote the infectivity of SARS-CoV-2. Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility 36,590 variant-specific RT-PCR tests were performed on samples collected between April 12 and May 7, 2021 in France to compare variant spread. Compared to January to March 2021, B.1.351 variant had a significant transmission advantage over B.1.1.7 in some regions (15.1 to 16.1% in Île-de-France and 16.1 to 18.8% in Hauts-de-France). This shift in transmission advantage is consistent with the immune evasion abilities of B.1.351 and the high levels of immunization in these regions. Roquebert 2021 https://doi.org/10.1101/2021.05.12.21257130 doi:10.1101/2021.05.12.21257130 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Assuming complete cross-protection, we estimate 501Y.V2/B.1.351 was 1.50 (95% CrI: 1.20-2.13) times as transmissible than previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure. Pearson 2021 https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Average ~10-fold reduction in neutralization efficacy in convalescent sera of 16 health workers infected in Spring 2020. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) with enrollment June 24 and November 9, 2020 from ~2000 HIV-negative 18-64 year olds (1:1 placebo to treatment), incidence of serious adverse events 14 or more days post- 2nd dose was balanced between the vaccine and placebo groups. A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. Serum samples obtained from 13 ChAdOx1 nCoV-19 vaccine recipients without SARS-CoV-2 infection through 41 days after vaccination showed 3.5x reduction in neutralization (ID50) for B.1.351 RBD pseudotype HIB-1 virus compared to D614G alone. This RBD variant combination's neutralization by a placebo control group of 6 naturally infected patients showed a similar 3.2x drop (though with D614G starting at a 1.7x higher titre than vaccinee sera). Madhi 2021 https://doi.org/10.1056/NEJMoa2102214 doi:10.1056/NEJMoa2102214 pmid:33725432 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Neutralizing antibody titers of 18 samples (90%) decreased against this B.1.351 pseudotyped virus below an ID50 threshold of 40 (sera collected ~8mo post Jan 2020 first wave in China). Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abolished neutralization by mAbs CQ026 and CQ038, greatly diminished neutralization by CQ012 and CQ046. Hu 2021 https://doi.org/10.1101/2021.01.22.427749 doi:10.1101/2021.01.22.427749 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant of key B.1.351 lineage mutations showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23011,23012,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed ~10x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23041,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trachea viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~750x fold drop in the R3P1-E4 antibody in comparison to the IgG control. Li 2022 https://doi.org/10.1186/s13578-022-00794-7 doi:10.1186/s13578-022-00794-7 pmid:35581593 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23041,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Lung viral loads were tested by qRT‑PCR and RNA scope at 3 dpi on 5 8‑month‑old male mice and there was a ~2266x fold drop in the R3P1-E4 antibody in comparison to the IgG control. Li 2022 https://doi.org/10.1186/s13578-022-00794-7 doi:10.1186/s13578-022-00794-7 pmid:35581593 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23041,23060,23061,23062,23062,23063,23063 K417N,K417N,K417N,K417N,K417N,K417N,K417N,Q493H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Gln493His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness 100% of the 5 8‑month‑old male R3P1-E4 antibody treated mice suvived 14 days after infection while only 60% the control group mice survived 5 days post infection. Li 2022 https://doi.org/10.1186/s13578-022-00794-7 doi:10.1186/s13578-022-00794-7 pmid:35581593 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~5x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied] Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (no synergy as level approx. that of N501Y alone). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22810,22810,22811,22812,22813,22813,22813,23399,23401,23401,23402,23403,23403 K417N,K417N,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811 K417D YP_009724390.1:p.Lys417Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Most and moderately effective mutant against this position in the RBD for moderately neutralizing COV2-2082 monoclonal antibody Mildly effective mutant against this position in the RBD for moderately neutralizing COV2-2094 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22811 K417D YP_009724390.1:p.Lys417Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, but moderate decrease in ACE2 binding affinity Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417I YP_009724390.1:p.Lys417Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812 K417I YP_009724390.1:p.Lys417Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.39 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 2.6 fold increase in IC50 of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.25 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 57.1 fold decrease in KD value for antibody binding of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-3C8. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes no detectable change in KD value for antibody binding of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 1.1 fold decrease in KD value of antibody binding of ACE2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Causes 2.9 fold decrease in KD value for antibody binding of P2C-1F11. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P22A-1D1. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The K417T mutation decreased the affinity ~2 fold, mainly by decreasing the k(on) but also by increasing the k(off) as measured by surface plasmon resonance. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~16x binding against this isolated mutation. Estesevimab lost ~16x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects No detectable fold drop in IC50 of P5A-1D2. Zhang 2021 https://doi.org/10.1038/s41467-021-24514-w doi:10.1038/s41467-021-24514-w pmid:34244522 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In vitro selection against class 1 antibody C682 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812 K417T,K417T ,NC_045512.2(GU280_gp02):g.1250A>C YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.64 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812,23011,23012,23060,23061,23062,23062,23063,23063 K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Tixagevimab, Regdanvimab and COR-101 display reduced binding affinity to virus pseudotyped as RBD from P.1. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812,23011,23012,23060,23061,23062,23062,23063,23063 K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The affinity of the P.1 RBD variants for ACE2 increased by 5.3 fold as measured by surface plasmon resonance relative to wild type RBD by increasing the k(on) and decreasing the k(off) rate constants. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The KD for the pseudotyped P.1-ACE2 interaction is 4.8 nM, showing that binding to P.1 is essentially indistinguishable from B.1.351 (4.0 nM), which binds with ~19x greater affinity that wild type. Dejnirattisai 2021 https://doi.org/10.1016/j.cell.2021.03.055 doi:10.1016/j.cell.2021.03.055 pmid:33852911 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2(GU280_gp02):g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2(GU280_gp02):g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2(GU280_gp02):g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2(GU280_gp02):g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2(GU280_gp02):g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2(GU280_gp02):g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2(GU280_gp02):g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22820 D420N NC_045512.2(GU280_gp02):g.1258G>A YP_009724390.1:p.Asp420Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22851 T430I NC_045512.2(GU280_gp02):g.1289C>T YP_009724390.1:p.Thr430Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22865 A435S NC_045512.2(GU280_gp02):g.1303G>T YP_009724390.1:p.Ala435Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to neutralizing mAb H014 (on D614G background) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Positive selection (up to 45% of supernatant sequences) under two rounds of C135 monoclonal antibody passage, eliminated in subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The N440K variant produced ten times higher infectious viral titers than a prevalent A2a strain, and over 1000 folds higher titers than a much less prevalent A3i strain prototype in Caco2 cells. Interestingly, A3i strain showed the highest viral RNA levels, but the lowest infectious titers in the culture supernatants, indicating the absence of correlation between the RNA content and the infectivity of the sample. Tandel 2021 https://doi.org/10.1101/2021.04.30.441434 doi:10.1101/2021.04.30.441434 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 0.7x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 3 antibody C669 mildly selected for the emergence of the N440K mutation in vitro (in contrast to N440H which caused mild escape in Class 1/2 mAb C653). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Greater than 10-fold reduction of binding effeiency vs wild type for mAb LY-CoV555. Abolishes binding of mAb ADG-1. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to class 3 antibodies (i.e. Abs that do not directly interfere with ACE2 binding). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 pmid:33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882 N440K,N440K,N440K,N440K,N440K,N440K YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects N501Y substitution decreased the neutralizing and binding activities of CB6 and increased that of BD-23 Cheng 2021 https://doi.org/10.1186/s12985-021-01554-8 doi:10.1186/s12985-021-01554-8 pmid:33910569 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22879,22879,22881,22882,22882,22882,23399,23401,23401,23402,23403,23403 N440K,N440K,N440K,N440K,N440K,N440K,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asn440Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection A 47yo Indian male was reinfected with B.1.36 lineage virus in September 2020 after infection with genetically distinct B.1.36 virus in July, with negative PCR tests in between. While the forst episode was asymptomatic, the second included fever, cough, and malaise. The second case additionally contained stopgain ORF3a:E261* Rani 2021 https://doi.org/10.1002/jmv.26997 doi:10.1002/jmv.26997 pmid:33818797 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444R NC_045512.2(GU280_gp02):g.1331A>G YP_009724390.1:p.Lys444Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Identified in 6/20 replicates of recombinant VSV growth in the presence of mAb COV2-2130. Dong 2021 https://doi.org/10.1101/2021.01.27.428529 doi:10.1101/2021.01.27.428529 pmid:33532768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893 K444R NC_045512.2(GU280_gp02):g.1331A>G YP_009724390.1:p.Lys444Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 20% of supernatant sequences) under two rounds of COV-NY convalescent plasma passage, eliminated in rounds three and four Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893,22893 K444T,K444T NC_045512.2(GU280_gp02):g.1331A>C, YP_009724390.1:p.Lys444Thr,YP_009724390.1:p.Lys444Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893,22893 K444T,K444T NC_045512.2(GU280_gp02):g.1331A>C, YP_009724390.1:p.Lys444Thr,YP_009724390.1:p.Lys444Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22893,22893 K444T,K444T NC_045512.2(GU280_gp02):g.1331A>C, YP_009724390.1:p.Lys444Thr,YP_009724390.1:p.Lys444Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Results in 3.7-fold drop in neutralization potency for COVA2-29, which is a cluster I RBD141 specific antibody. Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2(GU280_gp02):g.1332G>T,NC_045512.2(GU280_gp02):g.1332G>C YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2(GU280_gp02):g.1332G>T,NC_045512.2(GU280_gp02):g.1332G>C YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2(GU280_gp02):g.1332G>T,NC_045512.2(GU280_gp02):g.1332G>C YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects ~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2(GU280_gp02):g.1332G>T,NC_045512.2(GU280_gp02):g.1332G>C YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2(GU280_gp02):g.1332G>T,NC_045512.2(GU280_gp02):g.1332G>C YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2(GU280_gp02):g.1332G>T,NC_045512.2(GU280_gp02):g.1332G>C YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2(GU280_gp02):g.1332G>T,NC_045512.2(GU280_gp02):g.1332G>C YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2(GU280_gp02):g.1332G>T,NC_045512.2(GU280_gp02):g.1332G>C YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-01 and moderately resistant to 2H04 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2(GU280_gp02):g.1332G>T,NC_045512.2(GU280_gp02):g.1332G>C YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Improvement in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2(GU280_gp02):g.1332G>T,NC_045512.2(GU280_gp02):g.1332G>C YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Abolishes binding efficiency vs wild type for mAb REGN10933. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2(GU280_gp02):g.1332G>T,NC_045512.2(GU280_gp02):g.1332G>C YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22894,22894 K444N,K444N NC_045512.2(GU280_gp02):g.1332G>T,NC_045512.2(GU280_gp02):g.1332G>C YP_009724390.1:p.Lys444Asn,YP_009724390.1:p.Lys444Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Positive selection (up to 14% of supernatant sequences) after COV-NY convalescent plasma assay Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22895 V445P YP_009724390.1:p.Val445Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.05 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22896 V445A NC_045512.2(GU280_gp02):g.1334T>C YP_009724390.1:p.Val445Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 41% appearance in 2 passages against Regeneron monoclonal antibody RGN10987 @ 10ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 pmid:32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2(GU280_gp02):g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2499 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2(GU280_gp02):g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Decrease in neutralization capability of all 4 convalescent sera tested (1 ablated). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2(GU280_gp02):g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2(GU280_gp02):g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 1 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2(GU280_gp02):g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-02, SARS2-32 and SARS2-35 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22899 G446D NC_045512.2(GU280_gp02):g.1337G>A YP_009724390.1:p.Gly446Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed a ~4x drop in sensitivity. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2(GU280_gp02):g.1348A>T,NC_045512.2(GU280_gp02):g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Most effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2(GU280_gp02):g.1348A>G,NC_045512.2(GU280_gp02):g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2(GU280_gp02):g.1348A>G,NC_045512.2(GU280_gp02):g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2(GU280_gp02):g.1348A>G,NC_045512.2(GU280_gp02):g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 95% appearance in 2 passages against Regeneron monoclonal antibody RGN10934 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 pmid:32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2(GU280_gp02):g.1348A>T,NC_045512.2(GU280_gp02):g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations), triple replicates. Against a broader panel of 16 convalescent plasma (no replicates), reductions in neutralization are considerably less dramatic in pattern, and sometime neutralization increases. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2(GU280_gp02):g.1348A>T,NC_045512.2(GU280_gp02):g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2(GU280_gp02):g.1348A>T,NC_045512.2(GU280_gp02):g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2(GU280_gp02):g.1348A>G,NC_045512.2(GU280_gp02):g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2(GU280_gp02):g.1348A>G,NC_045512.2(GU280_gp02):g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-07 nd moderately resistant to SARS2-16 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2(GU280_gp02):g.1348A>T,NC_045512.2(GU280_gp02):g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450D,N450D NC_045512.2(GU280_gp02):g.1348A>G,NC_045512.2(GU280_gp02):g.1348A>G YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910 N450Y,N450Y NC_045512.2(GU280_gp02):g.1348A>T,NC_045512.2(GU280_gp02):g.1348A>T YP_009724390.1:p.Asn450Tyr,YP_009724390.1:p.Asn450Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 4 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22904,22910,23011,23012,23039,23039,23040,23373,25045,25046,25046 N450D,N450D,E484K,E484K,Q493R,Q493R,Q493R,T604I,P1162S,P1162S,P1162S YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Asn450Asp,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Thr604Ile,YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Artificially constructed HIV-1 pseudovirus with set of mutations drawn from plasma passage escape experiments shows ablated neutralization efficacy (NT50 ~ 0) in two of 21 convalescents plasma collected mean 1.3 months post infection. Greater than 4-fold reduction was observed in most of the other plasma. 14 vaccinee plasma showed a slightly lower reduction in efficacy, albeit from a higher average starting point titre than convalescents. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22905 N448S NC_045512.2(GU280_gp02):g.1343A>G YP_009724390.1:p.Asn448Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22907 Y449N NC_045512.2(GU280_gp02):g.1345T>A YP_009724390.1:p.Tyr449Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22907 Y449H NC_045512.2(GU280_gp02):g.1345T>C YP_009724390.1:p.Tyr449His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2(GU280_gp02):g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2(GU280_gp02):g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2(GU280_gp02):g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2(GU280_gp02):g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01 and SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2(GU280_gp02):g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2(GU280_gp02):g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912 N450K NC_045512.2(GU280_gp02):g.1350T>G YP_009724390.1:p.Asn450Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912,22912,22916 L452M,L452M,L452M ,NC_045512.2(GU280_gp02):g.1354C>A,NC_045512.2(GU280_gp02):g.1354C>A YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22912,22912,22916 L452M,L452M,L452M ,NC_045512.2(GU280_gp02):g.1354C>A,NC_045512.2(GU280_gp02):g.1354C>A YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met,YP_009724390.1:p.Leu452Met surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. [listed as L454R in Figure, but L452R in text, also text suggests not statistically significant, but error bars say otherwise in Figure 4] Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) entirely lost its neutralizing activity due to the central location of L452R in the epitopes recognized by this mAb. Regdanvimab (CT-P59), and to a smaller extent etesevimab, showed a reduction in neutralization potency. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2/3 antibody C628 and class 2 antibody C643 selected for the emergence of the L452R mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~5x binding against this isolated mutation. Cligavimab lost ~4x binding against this isolated mutation. Regdanvimab lost ~4x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.67 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Ablation of neutralization capability of 3 of 4 convalescent sera tested, the other is significantly hindered. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. L452R conferred about a two-fold reduction in neutralisation by vaccine sera, but was not statistically significant with this sample size. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 10 of 14 RBD-specific mAbs that showed at least 10-fold reduced neutralization of B.1.427/B.1.429 variant pseudotype (S13I, W152C, and L452R) were also found to poorly bind to just a L452R RBD mutant, demonstrating a role for this mutation as an escape mechanism for certain RBD-targeting mAbs. McCallum 2021 https://doi.org/10.1101/2021.03.31.437925 doi:10.1101/2021.03.31.437925 pmid:33821281 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion L452R derivative virus did not induce IFN-gamma expression even at the highest concentration tested (10 nM) in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456). Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs X593 and P2B-2F6 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects ~20% (ELISA significance threshold) drop in antibody binding (ELISA) by this variant against monoclonal antibody VH ab6. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02. Motozono 2021 https://doi.org/10.1016/j.chom.2021.06.006 doi:10.1016/j.chom.2021.06.006 pmid:34171266 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking We observed increased entry by pseudoviruses carrying the L452R mutation compared to D614G alone, with a 6.7 to 22.5-fold increase in 293T cells and a 5.8 to 14.7-fold increase in human airway organoids. Deng 2021 https://doi.org/10.1101/2021.03.07.21252647 doi:10.1101/2021.03.07.21252647 pmid:33758899 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to more than one antibody. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Observed ~2x decrease on average in neutralization efficacy in convalescent sera of 16 health workers. Alenquer 2021 https://doi.org/10.1101/2021.04.22.441007 doi:10.1101/2021.04.22.441007 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021 https://doi.org/10.1101/2021.04.14.21255431 doi:10.1101/2021.04.14.21255431 pmid:33907767 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 3 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.32 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Increased stability of RBD expression in yeast, suggesting increased Spike protein stability. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~1.7-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917 L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-02 and SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23011,23012 L452R,L452R,L452R,L452R,L452R,L452R,E484K,E484K YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant combination shows a ~4-5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, same as L452R alone. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23011,23012,23599,23599,23604,23604 L452R,L452R,L452R,L452R,L452R,L452R,E484K,E484K,P681R,P681R,P681R,P681R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant combination shows a ~3x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G, significantly less of a decrease than any B.1.617 lineage variants alone, suggesting a synergistic effect on cell entry while maintaining known immunity esacpe mutants. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012 L452R,L452R,L452R,L452R,L452R,L452R,E484Q YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484Q had a ~5x drop in neutralization (vs ~10x for E484K). When E484Q and L452R were combined, the fold change was significant, but similar to that of L452R alone (~2x), suggesting no evidence for an additive effect [perhaps even E484Q effect dilution]. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x infectivity advantage to the spike particles [less than L452R or E484Q alone working with the delins]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.617) showed a 1.85x increase in binding (KD) relative to D614G. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.4x reduction in neutralization (ID50) in sera 3 weeks after one dose of Pfizer/BioNTech BNT162b2 (up to 5 naive and post infection vaccinees) Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The combination caused a 3-fold increase in infectivity relative to D614G wild type. [compare to 3.5x for L452R alone] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Pseudotyped viruses for B.1.617 was 2.3-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. [details on the convalescent patient sera collection are not abundantly clear in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a ~3x drop in neutralization (NT50) [working with the delins, less than just L452R but more than just E484Q]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.617) showed a 1.30x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.18x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.617 was 4-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 5-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.617 was caused by the L452R and E484Q mutation, based on results from viruses pseudotyped for individual variants within B.1.617. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.617) showed a 1.22x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. [exact variant list not provided in manuscript, is inferred fro common knowledge] Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2.5x. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23599,23599,23604,23604 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,P681R,P681R,P681R,P681R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load In 9 infected hamsters each for B.1 and B.1.617.1, no significant change in viral load or subgenomic RNA levels were detected. Yadav 2021 https://doi.org/10.1101/2021.05.05.442760 doi:10.1101/2021.05.05.442760 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23599,23599,23604,23604 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,P681R,P681R,P681R,P681R YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence Gross examination of 3+3 hamster lung specimens showed pronounced congestion and hemorrhages on days 5 and 7 post-infection in the case of the B.1.617.1 as compared with the B.1. The lung lesions with the B.1 variant were minimal to mild whereas with B.1.617.1 they were moderate. For B.1 pneumonic changes were minimal to mild (inflammatory cell infiltration, focal consolidation and mild congestion). The pronounced changes (moderate to severe) with mononuclear infiltration in the alveolar interstitial space, interstitial septal thickening, consolidation and pneumocyte hyperplasia were observed with B.1.617.1 variant consistently. Yadav 2021 https://doi.org/10.1101/2021.05.05.442760 doi:10.1101/2021.05.05.442760 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23012,23599,23599,23604,23604,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,E484Q,P681R,P681R,P681R,P681R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Normalized for particle number, on ACE2.293T cells showed that the B.1.617 spike protein was >2-fold increase in infectivity relative to D614G wild type. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23060,23061,23062,23062,23063,23063 L452R,L452R,L452R,L452R,L452R,L452R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The presence of these B.1.417/B.1.429 defining variants in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021 https://doi.org/10.1101/2021.04.14.21255431 doi:10.1101/2021.04.14.21255431 pmid:33907767 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 7.42x drop in neutralization (NT50) [mostly from 3 of the sera]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a 1:5 test-negative matched control study of 8153 individuals who received the Moderna mRNA-1273 vaccine, 583 test-positive were Epsilon. Two dose vaccine efficacy against Epsilon was 97.6 (90.2-99.4%), one dose VE was 76.3 (48.1-89.1%). Bruxvoort 2021 https://doi.org/10.1101/2021.09.29.21264199 doi:10.1101/2021.09.29.21264199 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this RBD mutation conferred a 2.36x drop in neutralization (NT50). Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Increased infectivity of the B.1.617 spike was attributed to L452R, which itself caused a 3.5-fold increase in infectivity relative to D614G wild type. [In combination with E484Q caused a somewhat less 3-fold increase] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility The L452R mutation increased the infectivity more than two-fold in these conditions. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~2x infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22915,22915,22916,22916,22917,22917,23399,23401,23401,23402,23403,23403 L452R,L452R,L452R,L452R,L452R,L452R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 increased syncytium formation ~2x. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22916 L452W YP_009724390.1:p.Leu452Trp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked effective mutant against this position in the RBD for highly neutralizing COV2-2096 Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917 L452Q NC_045512.2(GU280_gp02):g.1355T>A YP_009724390.1:p.Leu452Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.27 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22917 L452Q NC_045512.2(GU280_gp02):g.1355T>A YP_009724390.1:p.Leu452Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2(GU280_gp02):g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion The induction level of IFN-gamma expression by the Y453F derivative in two different A*24:02 convalescent sera donor plasma (linear epitope NYNYLYRLF 448,456) was significantly lower. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2(GU280_gp02):g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Casirivimab lost >50x binding against this mutation. Hoffman 2021 https://doi.org/10.1016/j.celrep.2021.109017 doi:10.1016/j.celrep.2021.109017 pmid:33857422 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2(GU280_gp02):g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~4-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2(GU280_gp02):g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing modest decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2(GU280_gp02):g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed in 4 separate mink farms in Denmark, and Y453F is circulating relatively widely in humans. Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 pmid:33172935 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2(GU280_gp02):g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 pmid:33172935 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2(GU280_gp02):g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~12x binding against this double mutation. Casirivimab lost ~64x binding against this double mutation. Cligavimab lost ~6x binding against this double mutation. Estesevimab lost ~10x binding against this double mutation. Imdevimab lost ~5x binding against this double mutation. Regdanvimab lost ~8x binding against this double mutation. Sotrovimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2(GU280_gp02):g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2(GU280_gp02):g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*24:02. Motozono 2021 https://doi.org/10.1016/j.chom.2021.06.006 doi:10.1016/j.chom.2021.06.006 pmid:34171266 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2(GU280_gp02):g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape VSV pseudotyped with Y453F reduced inhibition by most of the 13 potent convalescent serum/plasma samples tested, albeit with variable efficiency (median increase of serum/plasma titer required for 50% neutralization [NT50] = 1.62x, range = 1.02x to 3.43x), indicating that this RBD mutation may compromise SARS-CoV-2 control by preexisting neutralizing antibody responses. Hoffman 2021 https://doi.org/10.1016/j.celrep.2021.109017 doi:10.1016/j.celrep.2021.109017 pmid:33857422 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2(GU280_gp02):g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 10-fold reduction in binding efficiency vs wild type for MAb REGN10933. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920 Y453F NC_045512.2(GU280_gp02):g.1358A>T YP_009724390.1:p.Tyr453Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.25 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22920,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766 Y453F,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del YP_009724390.1:p.Tyr453Phe,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence The so-called 'delta F' variant combination previously observed in mink spillover events also emerged in a lymphoma patient (non-Hodgkin diffuse B-cell lymphoma IV stage B) with a long-term COVID-19 infection (4 months) where 18 de novo mutation occureed overall. Patient was taking rituximab, the B-cell-depleting agent, and had no detectable neutralizing antibody response. Bazykin 2021 https://virological.org/t/emergence-of-y453f-and-69-70hv-mutations-in-a-lymphoma-patient-with-long-term-covid-19/580 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22926 L455S NC_045512.2(GU280_gp02):g.1364T>C YP_009724390.1:p.Leu455Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.45 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22926,22927,22927,22928,22930,22930 F456L,F456L,F456L,F456L,F456L,F456L NC_045512.2(GU280_gp02):g.1366T>C,NC_045512.2(GU280_gp02):g.1368T>A,NC_045512.2(GU280_gp02):g.1366T>C,NC_045512.2(GU280_gp02):g.1366T>C,NC_045512.2(GU280_gp02):g.1368T>G,NC_045512.2(GU280_gp02):g.1368T>A YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu,YP_009724390.1:p.Phe456Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects This double substitution reduces neutralization by RBD-specific mAbs from different clusters, specifically, the cluster I mAb COVA2-29, cluster III mAb COVA2-07 and cluster VI mAb COVA1-12. For COVA1-12 all neutralization activity is abolished, while COVA2-07 activity is just below the level required to calculate an IC50 value. Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22928 F456V NC_045512.2(GU280_gp02):g.1366T>G YP_009724390.1:p.Phe456Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Moderate in vitro selection against class 1 (Spike 'up' conformation) antibodies C683 and C664. Unclassified antibody C666 selected for the emergence of the F456V mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22928 F456V NC_045512.2(GU280_gp02):g.1366T>G YP_009724390.1:p.Phe456Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22936 K458N NC_045512.2(GU280_gp02):g.1374G>T YP_009724390.1:p.Lys458Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.09 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected with increasing proportion during in vitro evolution of Spike against ACE2 receptor Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22938,22939,22939,22942,22942,22942 N460K,N460K,N460K,N460K,N460K,N460K YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys,YP_009724390.1:p.Asn460Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460Y NC_045512.2(GU280_gp02):g.1378A>T YP_009724390.1:p.Asn460Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460H NC_045512.2(GU280_gp02):g.1378A>C YP_009724390.1:p.Asn460His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Mild escape mutant emergent for class 1 antibody C613 in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22940 N460H NC_045512.2(GU280_gp02):g.1378A>C YP_009724390.1:p.Asn460His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22941 N460S NC_045512.2(GU280_gp02):g.1379A>G YP_009724390.1:p.Asn460Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22941 N460I NC_045512.2(GU280_gp02):g.1379A>T YP_009724390.1:p.Asn460Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016 Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22964 I468V NC_045512.2(GU280_gp02):g.1402A>G YP_009724390.1:p.Ile468Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22964 I468V NC_045512.2(GU280_gp02):g.1402A>G YP_009724390.1:p.Ile468Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22971,22974 T470N,E471V NC_045512.2(GU280_gp02):g.1409C>A,NC_045512.2(GU280_gp02):g.1412A>T YP_009724390.1:p.Thr470Asn,YP_009724390.1:p.Glu471Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects This mutation prevents neutralization by COVA2-29 (cluster I), COVA2-07 (cluster III) and COVA2-02 (cluster VII). It also reduces the activity of the most potent mAb COVA1-18 (cluster I) by 3-fold, whereas this mAb is only minimally affected by other mutations. Moreover, TEI470-2NVP lowers the potency of the structurally unmapped non-RBD cluster XI mAb, COVA1-21, to the limit of detection. Thus, this mutation negatively impacts the most mAbs, including representatives from four separate epitope clusters. Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22976 I472V NC_045512.2(GU280_gp02):g.1414A>G YP_009724390.1:p.Ile472Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to neutralizing mAb X593 (on D614G background) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22976 I472V NC_045512.2(GU280_gp02):g.1414A>G YP_009724390.1:p.Ile472Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2(GU280_gp02):g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 pmid:33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2(GU280_gp02):g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2(GU280_gp02):g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~50x binding against this isolated mutation. Estesevimab lost ~8x binding against this isolated mutation. Sotrovimab lost ~30x binding against this isolated mutation. Tixagevimab lost ~15x binding against this isolated mutation. m396 lost ~8x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2(GU280_gp02):g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs 157, 247, CB6, P2C-1F11, B38, and CA1 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2(GU280_gp02):g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C102, C105 and C144 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 pmid:33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2(GU280_gp02):g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some class 1 (Spike 'up' conformation) antibodies tested. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22986 A475V NC_045512.2(GU280_gp02):g.1424C>T YP_009724390.1:p.Ala475Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2(GU280_gp02):g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.22 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2(GU280_gp02):g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2(GU280_gp02):g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows some resistence across all antibodies tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2(GU280_gp02):g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 2.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2(GU280_gp02):g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-07, SARS2-16 and SARS2-19 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2(GU280_gp02):g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 11 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2(GU280_gp02):g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 3 mAbs such as C135 that do not directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 pmid:33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2(GU280_gp02):g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mixed bag of mild positive and negative changes in neutralization capability of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), 10 show low neutralization. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2(GU280_gp02):g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 2 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2(GU280_gp02):g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 host variant dependency This mutation's measured interaction affinity with ACE2:p.S19P (0.03% minor allele frequency, found almost exclusively in African/African-Americans in the GnomAD database) was significantly lower than the predicted value, indicating that these mutations were not independent. This is consistent with the fact that the ACE2 residue S19 is adjacent to RBD residue S477 in the contact interface. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2(GU280_gp02):g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2(GU280_gp02):g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Increased affinity for ACE2: clade in Australia 2020-05-27 onward, clade in Europe 2020-08-08 onward Modelling shows flexible region in Spike RBD with residue S477 having the greatest rotational flexibility. Singh 2021 https://assets.researchsquare.com/files/rs-106969/v2_stamped.pdf False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992 S477N NC_045512.2(GU280_gp02):g.1430G>A YP_009724390.1:p.Ser477Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding, with increasing proportion in subsequent rounds. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,22995,23042 T478K,T478K,S494P NC_045512.2(GU280_gp02):g.1433C>A,NC_045512.2(GU280_gp02):g.1433C>A,NC_045512.2(GU280_gp02):g.1480T>C YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Thr478Lys,YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Combination of RBD mutations appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome complicated by diffuse alveolar hemorrhage, who was receiving anticoagulation therapy, glucocorticoids, cyclophosphamide, and intermittent rituximab and eculizumab. Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 pmid:33176080 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23011,23012 S477N,E484K,E484K YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~10x binding against this double mutation. Tixagevimab lost ~16x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23103 S477N,S514F NC_045512.2(GU280_gp02):g.1430G>A,NC_045512.2(GU280_gp02):g.1541C>T YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Ser514Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects While S477N itself is highly resistent to a broad range of monoclonal antibodies, combined with S514F high neutralization is restricted to only three antibodies in a broad screen. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23103 S477N,S514F NC_045512.2(GU280_gp02):g.1430G>A,NC_045512.2(GU280_gp02):g.1541C>T YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Ser514Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (2 ablations). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23103 S477N,S514F NC_045512.2(GU280_gp02):g.1430G>A,NC_045512.2(GU280_gp02):g.1541C>T YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Ser514Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-07 and SARS2-16 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23401,23402,23403,23403 S477N,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) symptom prevalence Compared to the clade 20A strains that predominated during phase 1 between March and May 2020, the Marseille-4 variant (characterized by this mutation plus N:p.M234I;A376T) was associated with a lower frequency of cough, rhinitis, and olfactory and gustatory disorders. By contrast, hypoxemia was more frequent in patients infected with the Marseille-4 variant. Fournier 2021 https://doi.org/10.1016/j.ijid.2021.03.068 doi:10.1016/j.ijid.2021.03.068 pmid:33785459 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23401,23402,23403,23403 S477N,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection 11 cases of re-infection with the 'Marseille-4' variant found within 1028 positive tests, where all of the earlier infections were from different strains. This lineage is also characterized by N:p.M234I;A376T Fournier 2021 https://doi.org/10.1016/j.ijid.2021.03.068 doi:10.1016/j.ijid.2021.03.068 pmid:33785459 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23401,23402,23403,23403 S477N,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was neutralized slightly less than D614G in 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 22992,23399,23401,23401,23402,23403,23403 S477N,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with the key mutations from 20A.EU2 lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23003 N481Y NC_045512.2(GU280_gp02):g.1441A>T YP_009724390.1:p.Asn481Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Minor variant in initial round of in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009 V483L NC_045512.2(GU280_gp02):g.1447G>C YP_009724390.1:p.Val483Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in all 4 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Remarkably, several of the E484 escape mutants were resistant to neutralization at the highest concentration (1:80 initial dilution) of all 4 convalescent sera tested. Against a wider panel of 16 convalescent plasma (no replicates), all but one show major resistance. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, 1B07, SARS2-32, SARS2-35 and SARS2-07 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape 'E484A rose in frequency in linkage with F486I, but since E484A is not an escape mutation in our maps it is not shown in other panels' Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 pmid:33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013 E484A,E484A,E484A,E484A NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C,NC_045512.2(GU280_gp02):g.1451A>C YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23061,23062,23062,23063,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 152 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 152 S pseudotype was resistant to neutralization. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23061,23062,23062,23063,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This Spike pseudotype for Day 152 virus from a chronically infected patient was completely resistent to REGN10933. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23018,23027,23060,23061,23062,23062,23063,23063 E484A,E484A,E484A,E484A,F486I,Y489H,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Phe486Ile,YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 152 virus from a chronically infected patient: although mAb C1A-B12 had no activity against this pseudotype, all three affinity optimized versions were active; the antibody containing the most mutations, C1A-B12.3, was the most potent (IC50 <0.5 μg/mL). Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23062,23063,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness 3rd exposure to antigen by Delta (B.1.617.2) (n=24) breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a 3rd mRNA vaccine dose in individuals aged 21 –63 years, median age=30 years. Data collected 5.5 months after 2nd vaccination. Wang 2022 https://doi.org/10.1101/2022.08.11.503601 doi:10.1101/2022.08.11.503601 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23062,23063,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In sera from 17 sero-positive blood donors, and 18 months post-infection (May 2020) sera from 17 health care workers in Sweden, a 40x drop in neutralization by Omicron (B.1.1.529) pseudotyped lentivirus was observed in HEK293T cells using the First WHO International Standard (20/136). Median IC50 reduction was ~6x for the blood donors, and ~4.5x for the health care workers. Sheward 2021 https://drive.google.com/file/d/1CuxmNYj5cpIuxWXhjjVmuDqntxXwlfXQ/view False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23062,23063,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In a Belgian study including 1,433,135 persons (vaccinated between July 2021 to April 2022) infection-acquired immunity offered additional protection against symptomatic infection with Omicron in vaccinated persons compared to those without previous infection, when the infection was up to one year previous. Braeye 2022 https://doi.org/10.1101/2022.05.09.22274623 doi:10.1101/2022.05.09.22274623 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23060,23061,23062,23062,23063,23063 E484A,E484A,E484A,E484A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2). Yuan 2022 https://doi.org/10.1101/2022.05.11.491588 doi:10.1101/2022.05.11.491588 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23010,23012,23013,23071,23071,23074,23074,23075,23075,22992,23060,23061,23062,23062,23063,23063 E484A,E484A,E484A,E484A,Y505H,Y505H,Y505H,Y505H,Y505H,Y505H,S477N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Glu484Ala,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Ser477Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using molecular dynamics simulation, ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations. Zhang 2022 https://doi.org/10.1101/2022.06.05.493249 doi:10.1101/2022.06.05.493249 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23012 E484R,E484R YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23012 E484R,E484R YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This is a two point mutation change giving this position the highest possible fitness, has higher affinity than circulating E484K variant. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23012 E484R,E484R YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.15 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23009,23012 E484R,E484R YP_009724390.1:p.Glu484Arg,YP_009724390.1:p.Glu484Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape This mutation occurred in 100% of sequenced virions after 12 passages and led to a 4-fold decrease in convalescent plasma neutralization activity Andreano 2020 https://doi.org/10.1101/2020.12.28.424451 doi:10.1101/2020.12.28.424451 pmid:33398278 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Subtype of the B.1.526 'New York' lineage, lentivirus pseudotyped with this mutation combination in showed 3.3x reduction in IC50 serum dilution concentration for 6 convalescent sera. Zhou 2021 https://doi.org/10.1101/2021.03.24.436620 doi:10.1101/2021.03.24.436620 pmid:33791698 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.6 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Analyzing responses to the E484K mutation seen in B.1.351 and P.1 variants, we noted that it did not fall in a region predicted to bind the HLAII alleles tested (table S4). The mutation appeared to have no substantial or differential impact on T cell responses. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 pmid:33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Nine stored sera from Pfizer BNT162b2 vaccinees were tested against a range of spike mutation bearing PV. E484K conferred a ten-fold reduction in neutralisation by vaccine sera. Ferreira 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Human sera from 5 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) neutralized this variant 3.4x less relative to reference USA-WA1/2020 strain. 8 convalescent plasma with weak IgG ELISA titre neutralized this variant 2.4x less relative to reference USA-WA1/2020 strain. One plasma failed to neutralize at all. 11 convalescent plasma with moderate IgG ELISA titre neutralized this variant 4.2x less relative to reference USA-WA1/2020 strain. 11 convalescent plasma with high IgG ELISA titre neutralized this variant 2.6x less relative to reference USA-WA1/2020 strain. Jangra 2021 https://doi.org/10.1016/S2666-5247(21 doi:10.1016/S2666-5247(21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in binding efficiency vs wild type for mAb LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotyped virus model ablates neutralization by RBD-directed mAbs 4-20, 2-4, 2-43, 2-30, 2-15, LY-Cov555, C121. Pseudotyped virus model impairs neutralization by RBD-directed mAb COV2-2196 (somewhat more than fully pseudotyped B.1.351 or live virus) Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384 and S2H58. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to all seven class 2 (Spike 'up' or 'down' conformation, RBD targeting) antibodies tested, with 10-fold or greater reduction in neutralization (plus notable reudction in two unclassfied mAbs). Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 4 antibodies, and broad low level resistence against much of the rest of the panel. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 pmid:33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Of 50 mAbs tested, major loss of neutralization observed for S2N28, S2X615, S2N12, S2X192, S2H7, S2X16, S2X58, S2H70, S2X613, S2D19, S2N22, S2D32, S2H58, S2M11, S2D106, S2X30. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy E484K pseudotyped VSV was tested for neutralization in a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection. A cohort of 12 Argentinian recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed a mean 2.8x decrease in neutralization effiacacy. Ikegame 2021 https://doi.org/10.21203/rs.3.rs-400230/v1 doi:10.21203/rs.3.rs-400230/v1 pmid:33851150 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding The only mutation in the B.1.351 lineage that appears to contribute to neutralization reduction (~1.7x across 10 convalescent sera from April 2020 infectees) Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody VH-Fc ab8 Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape As measured by surface plasmon resonance, RBD with the E484K mutation alone showed a mean 19.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma. Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant alone shows a ~5x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~16x binding against this isolated mutation. Casirivimab lost ~16x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape due to E484K [given Dec 2020-Apr 2021 time frame of the study, this is assumed to entail both Beta and Gamma lineages]. Chung 2021 https://doi.org/10.1136/bmj.n1943 doi:10.1136/bmj.n1943 pmid:34417165 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2 antibodies C627, C602, C671, C643, and class 2/3 antibody C603 selected for the emergence of the E484K mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with many monoclonal antibodies (C144/C002/C121/C104/C110). Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 pmid:33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 50% of supernatant sequences) after C121 monoclonal antibody assay, decreasing in subsequent passages Strong positive selection (up to 44% of supernatant sequences) after after one round of C144 monoclonal antibody passage, then waning on subsequent passages Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The neutralizing activity of 15/20 convalescent sera was significantly lower against this pseudotyped virus model Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 100% appearance in 2 passages against Regeneron monoclonal antibody REGN10989 @ 50ug/mL (99% after one passage) Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 pmid:32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no change in infection rate amongst the cells. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Individual variants appearing at <=30% frequency at day 21 in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then appearing all at >95% frequency at day 27. Chen 2021 https://doi.org/10.1101/2021.04.08.21254791 doi:10.1101/2021.04.08.21254791 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Neutralizing antibody titers of non-human primate sera after one or two doses of Ad26.COV2.S (Jannsen vaccine) against the variants containing the E484K substitution in the RBD were present but reduced (fold reduction between 3.35–7.78, 95% confidence interval all above twofold difference, one-sample t test). Solfrosi 2021 https://doi.org/10.1084/jem.20202756 doi:10.1084/jem.20202756 pmid:33909009 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported moderate increase in affinity compared to wild-type RBD on the cell surface (Kd = 38.5nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E48K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Significant decrease in neutralization across 15 of 16 sera tested 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Multiple individuals in two related households were infected with a newly acquired E484K mutation within the B.1.311 lineage. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient's quarantine period. Sabin 2021 https://doi.org/10.1101/2021.10.02.21264415 doi:10.1101/2021.10.02.21264415 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in all 4 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, ELISA tests show 10x reduced efficacy of a majority of isolated antibodies, but only a modest decrease for vaccine plasma overall. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-01, SARS2-02, 1B07, SARS2-16, SARS2-32, SARS2-35 and 2B04 of 10 antibodies tested, and moderately high resistance to the remaining. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012 E484K,E484K ,NC_045512.2(GU280_gp02):g.1450G>A YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Monoclonal antibodies 13G9 and 58G6 maintain fairly high neutralization potency, compared to others interfacing with E484K. Li 2021 https://doi.org/10.1101/2021.04.19.440481 doi:10.1101/2021.04.19.440481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,22597,22597,22599 E484K,E484K,R346K,R346K,R346K YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys,YP_009724390.1:p.Arg346Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In serial experiment of mAb 2B04 resistent mutation isolate E484K then selected against mAb 2H04, this combination caused escape from both mAbs, even though incubation simultaneously with both mAbs failed to yield this combination. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,22810,22810,22811,22812,22813,22813,22813 E484K,E484K,K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~32x binding against this double mutation. COR-101 lost ~160x binding against this double mutation. Casirivimab lost ~16x binding against this double mutation. Estesevimab lost ~32x binding against this double mutation. Regdanvimab lost ~4x binding against this double mutation. Tixagevimab lost ~12x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,22810,22810,22811,22812,22813,22813,22813,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 E484K,E484K,K417N,K417N,K417N,K417N,K417N,K417N,K417N,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~13x more infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,22810,22810,22811,22812,22813,22813,22813,23399,23401,23401,23402,23403,23403 E484K,E484K,K417N,K417N,K417N,K417N,K417N,K417N,K417N,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Approximately as infective as D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of the individual variants). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063 E484K,E484K,Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Omicron neutralizing antibodies is 0.686x the WT 1 month post-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.4 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Viral load from lung tissue from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 pmid:35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 1 receptor-binding-motif targeting antibodies COV2-2050, 1B07, COVOX-384, and S2H58. Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR22 had a 0.0015x fold change in IC50 in B.1.1.529 Omicron Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Omicron BA.5 have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In 20 sera from BNT162b2 mRNA vaccine inoculated participants, 6 displayed mild (2x) reductions in neutralization. This variant combination showed the highest reduction, but the magnitude of the differences was small compared to the >4x differences in HA-inhibition titers that have been used to signal potential need for a strain change in influenza vaccines. Xie 2021 https://doi.org/10.1038/s41591-021-01270-4 doi:10.1038/s41591-021-01270-4 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The neutralizing activity of vaccine was slightly to significantly lower against this variant combination in sera from all 24 patients with the BNT162b2 mRNA vaccine. (Fig. 4) [In stark contrast to this combination plus K417N, which had no effect (P<0.0001 vs. P=0.8774)] Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 2 doses of the BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~100x folds more significant in 3 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 pmid:35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Values taken 28 days after booster dose was given for BBIBP-CorVvaccine to 390 participants with 130 participants in the 0-14d-10m, 0-21d-10m and 0-28d-10m group. The geometric mean titers (GMT) of neutralizing antibody in 0-28d-10m and 0-21d-10m group were significantly higher than 0-14d-10m group at month 3, month 6 and month 10 after the second dose. A sharply decrease by 4.85-fold (GMT: 94.4-20.3), 4.67-fold (GMT: 134.4-28.8) and 4.49-fold (GMT: 145.5-32.4) was observed from day 28 to month 10 after the second dose in 0-14d-10m, 0-21d-10m and 0-28d-10m group, respectively, and they had similar decline kinetics. Yao T 2022 https://doi.org/10.1101/2022.06.22.22276690 doi:10.1101/2022.06.22.22276690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding Out of 10 individuals with 3 doses of the BNT162b2/BNT162b2/BNT162b2 vaccine, neutralizing titer in Omicron was ~17.5x folds more significant in 9 individuals. Arora 2022 https://doi.org/10.1038/s41423-022-00870-5 doi:10.1038/s41423-022-00870-5 pmid:35581351 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.4 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Omicron BA.5 neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently. Neerukonda 2022 https://doi.org/10.1101/2022.06.01.494385 doi:10.1101/2022.06.01.494385 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy Protection against symptomatic infection caused by Beta/Gamma (assumed by combined presence of N501Y and E484K) was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%). Nasreen 2021 https://doi.org/10.1101/2021.06.28.21259420 doi:10.1101/2021.06.28.21259420 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Infectious viral titers in lung tissue determined using a tissue culture infectious dose (TCID) assay in 10 hamsters showed that Omicron Molnupiravir (MK-4482) had no statistically significant change. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 pmid:35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Log10ID50 of Omicron neutralizing antibodies is 0.722x the WT pre-third dose of pfizer-BioNTech BNT162b2 in 13 Kidney transplant recipients (KTR) with median age of 55.5. McEvoy C 2022 https://doi.org/10.1101/2022.06.24.22276144 doi:10.1101/2022.06.24.22276144 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Viral load from oral swabs from 11 hamsters in 10 treatments for Omicron MK-4482 had the greatest drop 3 days post-infection determined by quantitative RT-PCR targeting sgE in comparison to Alpha MK-4482, Beta MK-4482 and Delta MK-4482. Rosenke 2022 https://doi.org/10.1172/jci.insight.160108 doi:10.1172/jci.insight.160108 pmid:35579953 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Trimeric proteins FSR16m had a 0.025x fold change in IC50 in B.1.1.529 Omicron Chonira 2022 https://doi.org/10.1101/2022.05.30.493765 doi:10.1101/2022.05.30.493765 pmid:35677079 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In the case of VOC B.1.1.7+E484K, the addition of the E484K mutation to N501Y further increased the affinity, to ~15 fold higher than WT RBD (KD ~5 nM), by further increasing the k(on) as measured by surface plasmon resonance. Because the higher k(on) could result in mass transfer limiting binding, we confirmed that the kinetic measurement for this variant was not substantially affected by varying levels of immobilization. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 19 convalescent human sera ~1mo post infection had mild to moderate resistance against all samples. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation ~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~12x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction (~additive effects of 501 and 484). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~6x more efficient S2 domain cleavage compared to wild type, compared to 4x by D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). [N501Y+D614G does not show an increase in cleavage, therefore a synergistic effect of the trio is implied] Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~11x, Vero ~10x, and Calu-3 ~11x. Compare to wild type at ~5x across cell types. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed >5x decrease in Pfizer sera (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23255,23257,23399,23401,23401,23402,23403,23403,25088 E484K,E484K,F565L,F565L,D614G,D614G,D614G,D614G,D614G,D614G,V1176F YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Phe565Leu,YP_009724390.1:p.Phe565Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The study demonstrated 1.92 and 1.09 fold reductions (ELISA) in the neutralizing titer against B.1.1.28.2 (P2) variant (n=2 authentic virus) in comparison with prototype D614G variant with 42 sera of BBV152 (a.k.a. Covaxin) vaccine recipients 2mo post-booster and 19 natural infections respectively. [exact P.2 sequences were not given, using the common defining SNPs] Sapkal 2021 https://doi.org/10.1101/2021.04.30.441559 doi:10.1101/2021.04.30.441559 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23255,23257,23399,23401,23401,23402,23403,23403,25088 E484K,E484K,F565L,F565L,D614G,D614G,D614G,D614G,D614G,D614G,V1176F YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Phe565Leu,YP_009724390.1:p.Phe565Leu,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Study 3001 on Ad26.COV2.S (Jannsen vaccine) conducted September 21, 2020 through January 22, 2021 overlaps the emergence and dominance of the P.1 & P.2 lineages of SARS-CoV-2 in Brazil. The Brazilian arm of the Phase 3 double blind study showed severe/critical disease VE of 81.9% (95% CI: 17.0-98.1), and moderate to severe/critical disease VE of 66.2% (95% CI: 51.0-77.1). Compare to 78.0% and 74.4% for North American arm of the study during the same period (with low B.1.351 prevalence). Of the 69.3% of mostly severe infections sequenced as of this report, 69.4% were of P.2 lineage [defining lineage SNPs reported here]. 2021 https://www.fda.gov/media/146217/download False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23399,23401,23401,23402,23403,23403 E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped viruses for B.1.618 was 2.7-fold resistant to neutralization by 6 BNT162b2 vaccine sera 28 days post-booster compared to wild type - a finding that was similar to that of the 3.4-fold resistance of the South Africa B.1.351 variant using the same assay. Neutralization by 3 Moderna vaccine sera 28 days post-booster was 3-fold resistant (vs. 2.2-fold for B.1.351). The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23399,23401,23401,23402,23403,23403 E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Pseudotyped viruses for B.1.618 was 2.5-fold resistant to neutralization by convalescent sera compared to wild type - a finding that was similar to that of the 3-fold resistance of the South Africa B.1.351 variant using the same assay. The resistance of B.1.618 was caused by the E484K mutation, based on results from viruses pseudotyped for individual variants within B.1.618. [details on the convalescent patient sera collection are not abundantly clear in the preprint] Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23399,23401,23401,23402,23403,23403 E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~2x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23399,23401,23401,23402,23403,23403 E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed only minor in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23011,23012,23399,23401,23401,23402,23403,23403,25088 E484K,E484K,D614G,D614G,D614G,D614G,D614G,D614G,V1176F YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Val1176Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped P.2 virus has reduced neutralization activity vs wild type: 5.8x (30 sera Pfizer median 9 days post 2nd dose) and 2.9x (35 sera Moderna median 18 days post 2nd dose). This was significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2(GU280_gp02):g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects >20% (ELISA significance threshold) drop in antibody binding by this variant against monoclonal antibody VH-Fc ab8. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2(GU280_gp02):g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This variant alone shows a 10x decrease in cell entry efficiency (RLU measurement in 293T cells) compared to D614G. Ferriera 2021 https://doi.org/10.1101/2021.05.08.443253 doi:10.1101/2021.05.08.443253 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2(GU280_gp02):g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~20x binding against this isolated mutation. Casirivimab lost ~4x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484T YP_009724390.1:p.Glu484Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2(GU280_gp02):g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 3 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, E484Q shows a notably resistant profile, comparable to or even more resistant than E484K at later time points (i.e. more resistant to immune cell somatic mutation evolution), see Figure 5a,b. Subject C 32 days post-infection showed >>10 fold reduction in neutralization, reducing to ~10-fold by day 104. Subject B 26 days post-infection showed ~10 fold reduction in neutralization, reducing to ~4x at day 113. Notably, Subject B also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 32, and no E484K immune escape at day 104. Subject I 26 days post-infection showed ~10 fold reduction in neutralization, with no reduction in escape at day 102. Notably, Subject I also showed smaller than typical (~10 vs 30+ fold) reduction in one-month neutralization by E484K at day 26, and no E484K immune escape at day 102. Greaney 2021 https://doi.org/10.1016/j.chom.2021.02.003 doi:10.1016/j.chom.2021.02.003 pmid:33592168 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484Q NC_045512.2(GU280_gp02):g.1450G>C YP_009724390.1:p.Glu484Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012 E484T YP_009724390.1:p.Glu484Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23401,23402,23403,23403 E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD+RBD mutation combination from B.1.617.3 conferred a 1.34x drop in neutralization (NT50) [mostly from a single serum]. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23401,23402,23403,23403 E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD+RBD mutation combination from B.1.617.3 conferred a ~4x infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23401,23402,23403,23403 E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, RBD-specific mutation E484Q did not significantly confer infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23012,23399,23401,23401,23402,23403,23403 E484Q,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Glu484Gln,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23013 E484V NC_045512.2(GU280_gp02):g.1451A>T YP_009724390.1:p.Glu484Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23013 E484V NC_045512.2(GU280_gp02):g.1451A>T YP_009724390.1:p.Glu484Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2050 monoclonal antibody Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2479 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23017,23018 F486P,F486P YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.22 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23017,23018 F486P,F486P YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23017,23018 F486P,F486P YP_009724390.1:p.Phe486Pro,YP_009724390.1:p.Phe486Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2(GU280_gp02):g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 88% appearance in 2 passages against Regeneron monoclonal antibody RGN10933 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 pmid:32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2(GU280_gp02):g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked modestly effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486A YP_009724390.1:p.Phe486Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Most effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2(GU280_gp02):g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486A YP_009724390.1:p.Phe486Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2(GU280_gp02):g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutation causes a greater than 100x fold change in IC50 of Ensovibep. Rothenberger 2021 https://doi.org/10.1101/2021.02.03.429164v4 doi:10.1101/2021.02.03.429164v4 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486I NC_045512.2(GU280_gp02):g.1456T>A YP_009724390.1:p.Phe486Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2(GU280_gp02):g.1456T>C YP_009724390.1:p.Phe486Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486H YP_009724390.1:p.Phe486His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.05 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2(GU280_gp02):g.1456T>C YP_009724390.1:p.Phe486Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed in 4 separate mink farms in Denmark, but not humans, potential adaptation (diff set of farms than N501T). Oude Munnink 2020 https://doi.org/10.1126/science.abe5901 doi:10.1126/science.abe5901 pmid:33172935 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486L NC_045512.2(GU280_gp02):g.1456T>C YP_009724390.1:p.Phe486Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This mutation causes a greater than 100x fold change in IC50 of Ensovibep. Rothenberger 2021 https://doi.org/10.1101/2021.02.03.429164v4 doi:10.1101/2021.02.03.429164v4 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486V NC_045512.2(GU280_gp02):g.1456T>G YP_009724390.1:p.Phe486Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.07 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018 F486I NC_045512.2(GU280_gp02):g.1456T>A YP_009724390.1:p.Phe486Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 pmid:33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects >60% drop in antibody binding (ELISA) by this variant against monoclonal antibody VH-Fc ab8. Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 1 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows high resistence to 5 antibodies. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Modest decrease in in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAbs SARS2-07, SARS2-19, 1B07, SARS2-16 and 2B04 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.13 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape IC50 relative to wildtype drops ~8x in neutralization efficiency between 7-17 days post symptoms onset. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In a soluble human ACE2-Fc receptor decoy inhibition experiment, this mutation showed striking resistance with only 38% neutralization at the highest concentration tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked moderately effective mutant against this position in the RBD for highly neutralizing COV2-2832 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Wuhan-Hu-1 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23018,23019,23019 F486S,F486S,F486S YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser,YP_009724390.1:p.Phe486Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23023 N487K NC_045512.2(GU280_gp02):g.1461T>G YP_009724390.1:p.Asn487Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, high ACE2 binding affinity loss Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2(GU280_gp02):g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV016, minimal ACE2 binding affinity loss Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2(GU280_gp02):g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escapes mAb REGN10933 (part of Regeneron's antibody cocktail) Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 pmid:33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2(GU280_gp02):g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.11 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027 Y489H NC_045512.2(GU280_gp02):g.1465T>C YP_009724390.1:p.Tyr489His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Based on structural modelling, this change detected on day 128 sequencing in a chronically infected patient would alter an extensive network of polar interactions with antibody residue R94VH, a germline antibody residue that is conserved in all of the potent VH3-53/3-66-derived antibodies isolated from a convalescent donor 5 weeks after infection. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody ab8 Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape No effective neutralization in 3 out of the 4 sera tested. Liu 2021 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 1/2 mRNA vaccines results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected minor variants in an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2/3 mAb C603 modestly selected for the emergence of this mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Strong reduction in neutralization capability of all 4 convalescent sera tested (3 ablations). Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-32. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron BA.2 RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes due to 3 mRNA vaccine doses results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-32 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Inhibition of Omicron (B.1.1.529 [BA.1]) RBD point mutant pseudotypes under no vaccination results in high relative infection for this mutation, for individuals previously infected. Witte 2022 https://doi.org/10.1101/2022.08.17.504313 doi:10.1101/2022.08.17.504313 pmid:36032981 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23029,23029,23030,23031,23031 F490S,F490S,F490S,F490S,F490S,F490S YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser,YP_009724390.1:p.Phe490Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23039,23060,23061,23062,23062,23063,23063 Y489H,Q493K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 146 virus from a chronically infected patient, neutralizing activity of purified IgG from 3 donors was mostly unaffected by the single mutations (Q493K/R or N439K), but the day 146 S pseudotype was resistant to neutralization. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23039,23060,23061,23062,23062,23063,23063 Y489H,Q493K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Pseudotype for Day 146 virus from a chronically infected patient: resistant to neutralization by mAb C1A-B12, and was still resistant to the affinity enhanced antibodies derived from it (i.e. no affinity maturation effect on neutralization). Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23027,23039,23060,23061,23062,23062,23063,23063 Y489H,Q493K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Tyr489His,YP_009724390.1:p.Gln493Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This Spike pseudotype for Day 146 virus from a chronically infected patient was completely resistent to REGN10933. The variant had a 4-fold decrease in REGN10987 neutralization sensitivity (2nd component of the Regeneron mAb cocktail). Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2(GU280_gp02):g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Positive selection (up to 23% of supernatant sequences) after C121 monoclonal antibody assay Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2(GU280_gp02):g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Complete loss of binding in ELISA by the variant against monoclonal antibody ab8 Sun 2021 https://doi.org/10.1101/2021.03.22.436481 doi:10.1101/2021.03.22.436481 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490P YP_009724390.1:p.Phe490Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2(GU280_gp02):g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects For highly potent RBD-binding neutralizing antibody ADI-56443 this mutation causes ablation of neutralization efficiency. Haslwanter 2021 https://doi.org/10.1101/2021.06.10.447999 doi:10.1101/2021.06.10.447999 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490V NC_045512.2(GU280_gp02):g.1468T>G YP_009724390.1:p.Phe490Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Ranked mildly effective mutant against this position in the RBD for highly neutralizing COV2-2496 monoclonal antibody Greaney 2020 https://doi.org/10.1016/j.chom.2020.11.007 doi:10.1016/j.chom.2020.11.007 pmid:33259788 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2(GU280_gp02):g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) resistant to 3 individual sera at >4x Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490L NC_045512.2(GU280_gp02):g.1468T>C YP_009724390.1:p.Phe490Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to some neutralizing antibodies: mAbs X593, 261-262, H4, and P2B-2F6 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23030 F490P YP_009724390.1:p.Phe490Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2(GU280_gp02):g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2(GU280_gp02):g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Selected as minor variant in later rounds of an in vitro evolution experiment for ACE2 binding. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23031 F490Y NC_045512.2(GU280_gp02):g.1469T>A YP_009724390.1:p.Phe490Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.1 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039 Q493K NC_045512.2(GU280_gp02):g.1477C>A YP_009724390.1:p.Gln493Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Combo observed first in a mouse-adapted SARS-CoV-2 strain (MA10). Leist 2020 https://doi.org/10.1016/j.cell.2020.09.050 doi:10.1016/j.cell.2020.09.050 pmid:33031744 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039 Q493K NC_045512.2(GU280_gp02):g.1477C>A YP_009724390.1:p.Gln493Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Intermittent appearance at Day 128 onward of long infection in patient on escalated immunosupressed starting Day 111 Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 pmid:33176080 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039 Q493K NC_045512.2(GU280_gp02):g.1477C>A YP_009724390.1:p.Gln493Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039 Q493K NC_045512.2(GU280_gp02):g.1477C>A YP_009724390.1:p.Gln493Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Leads to a 14-fold reduction in neutralization efficiency for REGN10933. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039 Q493K NC_045512.2(GU280_gp02):g.1477C>A YP_009724390.1:p.Gln493Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escapes mAb REGN10987, part of Regeneron's antibody cocktail. Starr 2020 https://doi.org/10.1101/2020.11.30.405472 doi:10.1101/2020.11.30.405472 pmid:33299993 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039 Q493K NC_045512.2(GU280_gp02):g.1477C>A YP_009724390.1:p.Gln493Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 45% of supernatant sequences) under two rounds of C121 monoclonal antibody passage Strong positive selection (up to 39% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039 Q493K NC_045512.2(GU280_gp02):g.1477C>A YP_009724390.1:p.Gln493Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutation from chronically infected patient predicted to introduce clash with potent mAbs C1A-VH3-53, and verified by pseudovirus assay against the weaker mAbs in this family. The mutation conferred decreased sensitivity to mAb B38 but had no effect on neutralization by mAb CC12. Clark 2021 https://doi.org/10.1016/j.cell.2021.03.027 doi:10.1016/j.cell.2021.03.027 pmid:33831372 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Strong positive selection (up to 37% of supernatant sequences) after two rounds of C135 monoclonal antibody passage, overall 76% switch away from Q493 to K or R Weisblum 2020 https://doi.org/10.1101/2020.07.21.214759 doi:10.1101/2020.07.21.214759 pmid:32743579 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape The engineered mutation cause 10-fold or more increase in the disassociation constant with C144, C002 and C121 monoclonal antibodies vs. wild type Spike protein RBD domain AAs. Barnes 2020 https://doi.org/10.1038/s41586-020-2852-1 doi:10.1038/s41586-020-2852-1 pmid:33045718 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Class 2 mAb C627 modestly selected for the emergence of this mutation in vitro. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Dominant (70%) in day 21 of prolonged infection in immunocompromised host on tacrolimus, steroids and convalescent plasma therapy, then nearly disappearing (<5%) by day 27. Chen 2021 https://doi.org/10.1101/2021.04.08.21254791 doi:10.1101/2021.04.08.21254791 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates binding by class 2 mAbs such as C144 that directly interfere with ACE2 binding, but clonal somatic mutations of memory B cells at 6.2 months (evolving humoral immune response) show pronounced increase in binding to the variant. Gaebler 2021 https://doi.org/10.1101/2020.11.03.367391 doi:10.1101/2020.11.03.367391 pmid:33173867 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Somewhat resistent to some class 1 (Spike 'up') antibodies tested. Mix of non- to strongly resistent in class 2 antibodies tested. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23039,23039,23040 Q493R,Q493R,Q493R YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg,YP_009724390.1:p.Gln493Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Massive reduction in binding efficiency vs wild type for mAbs CB6/LY-CoV16 and LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2(GU280_gp02):g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mixed bag of positive and negative changes in neutralization capability of all 4 convalescent sera tested. Liu 2021 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2(GU280_gp02):g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using molecular dynamic simulation, the mildly (~1kcal/mol) enhanced binding energy of this variant is primarily contributed by Tyr505 (−4.98 kcal/mol) which is now involved in a strong hydrogen bonding network with Arg393. Another important energetic contribution comes from the altered orientation of Tyr41 which is now involved with two hydrogen-bonding interactions with Asp355 and Thr500. 2021 https://doi.org/10.1016/j.bbrc.2021.01.035 doi:10.1016/j.bbrc.2021.01.035 pmid:33602511 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2(GU280_gp02):g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~8x binding against this isolated mutation. Regdanvimab lost ~32x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2(GU280_gp02):g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Greater than 10-fold rediuction of binding effeiency vs wild type for mAb LY-CoV555. Rappazzo 2021 https://doi.org/10.1126/science.abf4830 doi:10.1126/science.abf4830 pmid:33495307 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2(GU280_gp02):g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Mutant screen in neutralization assay with a broad range of monoclonal antibodies shows resistence to mAb SARS2-01. Liu 2020 https://doi.org/10.1101/2020.11.06.372037 doi:10.1101/2020.11.06.372037 pmid:33442690 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2(GU280_gp02):g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape mutation against monoclonal antibody LY-CoV555 (antibody that forms the basis for Eli Lilly's bamlanivimab) Starr 2021 https://doi.org/10.1101/2021.02.17.431683 doi:10.1101/2021.02.17.431683 pmid:33655250 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2(GU280_gp02):g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Highly resistant to mAb SARS2-01 of 10 antibodies tested. Liu 2020 https://doi.org/10.1016/j.chom.2021.01.014 doi:10.1016/j.chom.2021.01.014 pmid:33535027 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2(GU280_gp02):g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Minor variant selected in late rounds of an in vitro evolution experiment for ACE2 binding. Shown to increase the thermostability but decrease the association rate constant of the RBD to ACE2 Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23042 S494P NC_045512.2(GU280_gp02):g.1480T>C YP_009724390.1:p.Ser494Pro surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape In 2 of 11 subjects' convalescent sera in an early+late mutational landscape analysis of the RBD, S484P shows a slightly resistant profile across both timepoints (i.e. resistant to immune cell somatic mutation evolution) Greaney 2021 https://doi.org/10.1016/j.chom.2021.02.003 doi:10.1016/j.chom.2021.02.003 pmid:33592168 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23048 G496S NC_045512.2(GU280_gp02):g.1486G>A YP_009724390.1:p.Gly496Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23053,23053,23054,23054,23055,23055,23060,23061,23062,23062,23063,23063 Q498R,Q498R,Q498R,Q498R,Q498R,Q498R,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Gln498Arg,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Y501 makes a pi interaction with Y41 and places R498 to make a hydrogen bond and salt bridge to Q42 and D38 of ACE2, forming a strong network of new interactions supporting the impact of these residues on affinity. Q498R alone appears to decrease ACE2 binding. The synergism of Q498R with N501Y (and E484K) increases ACE2 binding by ~50- fold relative to WT. The extent of affinity increase with Q498R and N501Y is not exactly quantified, as E484K always emerged with this duo during in vitro evolution. Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using Microscale Thermopheresis, this variant binds ACE2 at nearly two-fold greater affinity than the original SARS-COV-2 RBD (203.7 nM vs 402.5 nM). Ramanathan 2021 https://doi.org/10.1101/2021.02.22.432359 doi:10.1101/2021.02.22.432359 pmid:33655251 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Decreased stability of RBD expression in yeast, suggesting decreased Spike protein stability. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity N501Y residue inserts into a cavity at the binding interface near Y41 of ACE2. The additional interactions result in increased affinity of ACE2 for the N501Y mutant, accounting for its increased infectivity. Zhu 2021 https://doi.org/10.1101/2021.01.11.426269 doi:10.1101/2021.01.11.426269 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.69 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 4-fold increase in affinity compared to wild-type RBD on the cell surface (Kd = 13.1nM vs 56.9nM). Tian 2021 https://doi.org/10.1101/2021.02.14.431117 doi:10.1101/2021.02.14.431117 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Experimentally, ACE2 binding affinity increased 0.24 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Utilizing shark derived vnarbodies, S375F mutation on Omicron RBD disrupts the structure of β-strand, which inhibits binding with 20G6. 20G6 binds to a hidden epitope on RBD which is highly conserved in sarbecoviruses. Feng 2022 https://doi.org/10.1002/smtd.202200387 doi:10.1002/smtd.202200387 pmid:35583124 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This single mutation causes major increase in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus, but combined with the complete set of B.1.1.7 lineage variants no major change vs wild type affnity is observed. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity ~4-fold increase in binding affinity vs wild type. Motozono 2021 https://doi.org/10.1101/2021.04.02.438288 doi:10.1101/2021.04.02.438288 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In silico methods (PyMOL and PDBePISA) involving mutagenesis (N501Y mutation) and interface analysis focusing on the Spike RDB-ACE2 interaction showed that the SARS-CoV-2 N501Y mutant (lineage B.1.1.7) establishes a more significant number of interactions relating to the mutant residue Y501 (Spike RDB) with residues Y41 and K353 (ACE2). This finding shows that the increased infectivity of SARS-CoV-2 lineage B.1.1.7 is associated with the interaction force between the Spike RBD Y501 mutant residue with the ACE2 receptor, which in this strain is increased. 2021 https://doi.org/10.1101/2020.12.29.424708 doi:10.1101/2020.12.29.424708 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Reported 10-fold increase in ACE2 binding vs wildtype (Kd = 0.566nM vs 5.768 nM) Liu 2021 https://doi.org/10.1101/2021.02.02.428884 doi:10.1101/2021.02.02.428884 pmid:33564771 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Among the first selected and fixed variants in an in vitro evolution experiment for ACE2 binding. Calculated disassociation constant for this variant is nearly four fold lower than wild type (Kd = 455 pM vs 1600pM) Zahradnik 2021 https://doi.org/10.1101/2021.01.06.425392 doi:10.1101/2021.01.06.425392 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The most frequent RBM mutation N501Y (165,519 instances) makes defective the atypical N-glycosylation sequon NGV 501-503, becoming a key RBM position for the interaction with hACE2-binding hotspot 353. Gamez 2021 https://doi.org/10.1101/2021.04.09.439154 doi:10.1101/2021.04.09.439154 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Viruses containing the point mutations of B.1.1.7 showed that the single point mutations (Δ69-70 and N501Y) were neutralized as efficiently as D614G across 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding In 30 samples collected 111 to 260 days post onset of symptoms, the covalescent plasma can neutralize both the reference USA-WA1/2020 strain and the mouse adapted strain that contains the N501Y spike mutation with similar efficiency. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 pmid:33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~8x binding against this isolated mutation. Regdanvimab lost ~6x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 3% to 1.2% (poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del, A570D, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 or 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects 4 antibodies tested were less potent against K417N by ten-fold or more, in both mAb classes 1 and 3 Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Reduction in neutralization by mAbs COVA1-18 (~4x), COVA2-15 (~9x), S309 (~3x) Shen 2021 https://doi.org/10.1101/2021.01.27.428516 doi:10.1101/2021.01.27.428516 pmid:33532764 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Lowered the neutralization potency of mAb COVA1-12 to the limit of the assay. Decrease in potency was observed against the N501Y pseudotype for the cluster IX mAb COVA2-17. Rees-Spear 2021 https://doi.org/10.1101/2021.01.15.426849 doi:10.1101/2021.01.15.426849 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Appeared (day 128) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 pmid:33176080 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape 0.7x reduction in neutralization by key variant in several variants of concern in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation alone accounts for most of the increased infectivity of the Alpha variant, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters, and Vero E6 (NHP) and Calu-3 (human) cell lines. Liu 2021 https://doi.org/10.1101/2021.03.08.434499 doi:10.1101/2021.03.08.434499 pmid:33758836 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape As measured by surface plasmon resonance, RBD with the N501Y mutation alone showed a mean 2.1x decrease in binding affinity for six batches of hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma. Tang 2021 https://doi.org/10.1101/2021.03.19.436183 doi:10.1101/2021.03.19.436183 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity The N501Y mutation had the biggest effect on ACE2 affinity of any VOC mutation tested, increasing the affinity ~10 fold to KD ~7 nM, by increasing the k(on) ~1.8 fold and decreasing the k(off) by ~ 7 fold as measured by surface plasmon resonance. Barton 2021 https://doi.org/10.1101/2021.05.18.444646 doi:10.1101/2021.05.18.444646 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine efficacy In this Canadian test-negative study of 324033 individuals, two doses of either mRNA vaccine (BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)) was not associated with appreciable vaccine escape by lineage Alpha [defined here as N501Y positive, but E484K negative]. Chung 2021 https://doi.org/10.1136/bmj.n1943 doi:10.1136/bmj.n1943 pmid:34417165 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Vaccinated, but not post-infection sera, show decreased average T cell response to an N501Y peptide. When we primed transgenic mice expressing human HLA-DRB1*0401 with the Wuhan Hu-1 peptide pool, T cell responses to the B.1.1.7 variant peptide pool were significantly reduced (p = 0.0286). Furthermore, the T cell response to the spike N501Y mutation common to all three of the current VOC was ablated. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 pmid:33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy 1.2x drop in neutralization using sera collected from 14 healthy adult participants that received two injections of the mRNA-1273 (Moderna) vaccine at a dose of 100 µg (18-55 years; day 1 and day 14 post-2nd dose) against a recombinant single variant virus (modified replicating WA-1 cDNA clone) relative to contemporary circulating D614G variant (USA/GA-EHC-083E/2020) using a live-virus Focus Reduction Neutralization Test (FRNT) assay. Edara 2021 https://doi.org/10.1101/2021.02.02.21250799 doi:10.1101/2021.02.02.21250799 pmid:33564782 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In a cohort of 20 patients 8+ weeks after second vaccine dose of Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines, a modest decrease in neutralization by vaccine plasma was observed. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy The presence of this variant in 189 post-mRNA-vaccination COVID-19 cases was proportionally in line with lineage prevalence in Northen California during the study period, suggesting no effect of these variants on immune escape. Jacobson 2021 https://doi.org/10.1101/2021.04.14.21255431 doi:10.1101/2021.04.14.21255431 pmid:33907767 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Human sera from 6 two-dose Pfizer vaccinated individuals (47-68 days post 1st-dose) can neutralize both the reference USA-WA1/2020 strain and the mouse adapted SARS-CoV-2 strain that contains the N501Y spike mutation with similar efficiency. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 pmid:33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Contrary to other reports on N501Y containing lineages (i.e. with additional mutations), N501Y alone may have an even greater affinity for a human monoclonal antibody specific for wild type. These results suggest that the individual N501Y mutation does not contribute to altered viral properties by itself, but may contribute to a collective conformational shift produced by multiple mutations. Klegerman 2021 https://doi.org/10.1101/2021.04.26.441517 doi:10.1101/2021.04.26.441517 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slightly increased infection rate amongst the cells. [in what is essentially a replicate experiment in the same paper, because each B.1.351 lineage variant was independetly evaluated and N501 is in both lineages, a significant decrease was observed, therefore the error bars described in this paper should be interpreted carefully] Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Observed 1.3-fold reduction in neutralization efficiency of Pfizer vaccinee sera (collected 14 days after second dose) against pseudotype B.1.1.7 key variant lentivirus. Compare to 2.6-fold reduction against cultured B.1.1.7 virus. Bates 2021 https://doi.org/10.1101/2021.04.04.21254881 doi:10.1101/2021.04.04.21254881 pmid:33851185 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy Variant within the six key residues in the receptor binding domain (RBD). Independently reported in UK, Australia (same origin as UK), and South Africa (independent origin). Flores-Alanis 2021 https://doi.org/10.3390/pathogens10020184 doi:10.3390/pathogens10020184 pmid:33572190 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape In vitro selection against class 1 (Spike 'up' conformation) monoclonal antibody C663, and to a lesser extent C613. Wang 2021 https://doi.org/10.1101/2021.01.15.426911 doi:10.1101/2021.01.15.426911 pmid:33501451 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Of 50 mAbs tested, major loss of neutralization observed for S2X128, S2D8, S2X192, S2D19, S2H14, S2H19. Collier 2021 https://doi.org/10.1038/s41586-021-03412-7 doi:10.1038/s41586-021-03412-7 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,22810,22810,22811,22812,22813,22813,22813 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness COR-101 lost ~20x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~6x binding against this double mutation. M396 lost ~10x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,22810,22810,22811,22812,22813,22813,22813,23011,23012 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy In post-vaccination sera from individuals who received one (3 weeks post-first dose; n = 5) or two doses (9–11 days post-second dose; n = 10) of the BNT162b2 Pfizer vaccine, an average 6.8x reduction in neutralization efficacy of this B.1.351 key variants pseudotype lentivirus vs D614G was observed. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,22810,22810,22811,22812,22813,22813,22813,23011,23012 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape ~7x reduction in neutralization by key B.1.351 lineage RBD variant combination in sera collected from cohort of 10 with severe disease 21 to 63 days post-onset. Two of the cohort showed no neutralization against this variant. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,23011,23012 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,E484K,E484K YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness Bamlanivimab (LY-CoV555) lost ~64x binding against this double mutation. COR-101 lost ~50x binding against this double mutation. Casirivimab lost ~250x binding against this double mutation. Estesevimab lost ~16x binding against this double mutation. Regdanvimab lost ~32x binding against this double mutation. Tixagevimab lost ~10x binding against this double mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,23271 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) reinfection Partial sequencing of S gene reveals two cases of probable early 2021 B.1.1.7 lineage reinfection from non-B.1.1.7 original cases in Lombardy, with 45 to 90 days between infections (less than the typical 90 day guideline for this call). Patients were 56 and 58yo, immunocompenent, with one a former smoker with obesity and dyslipidemia. One case required intubation during first infection, but presented with mild symptoms upon reinfection. The other case convalesced at home during the first episode, but required CPAP support in the subacute clinical unit upon reinfection. Novazzi 2021 https://doi.org/10.1002/jmv.27066 doi:10.1002/jmv.27066 pmid:33969504 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation ~50% Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, signficantly higher than D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy This variant showed no change in Pfizer sera (one or two dose) neutralization efficiency vs D614G (using lentivirus pseudotype). Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~13x, Vero ~10x, and Calu-3 ~10x. Compare to wild type at ~5x across cell types. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking 9x more infectivity than D614G alone in HEK293T-ACE2 cells 48h post-transduction. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking More efficient infectivity (24h) compared to wild type, in Caco-2 cells ~9x, Vero ~8x, and Calu-3 ~8x. Compare to wild type at ~5x across cell types. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing no significant change in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding Lentiviral pseudotyped with the key mutations from COH.20G/677H ('Ohio') lineage was neutralized similarly to D614G in 10 convalescent sera from April 2020 infectees. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,23399,23401,23401,23402,23403,23403,23593,23593 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D614G,D614G,D614G,D614G,D614G,D614G,Q677H,Q677H YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Gln677His,YP_009724390.1:p.Gln677His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Lentiviral pseudotyped with the key mutations from COH.20G/677H lineage was tested on ACE2.293T cells for ACE2 affinity changes vs D614G alone, showing a ~70% drop in IC50 (i.e. increased affinity). Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525 N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 pmid:33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23071,23071,23074,23074,23075,23075 Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.16 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23071,23071,23074,23074,23075,23075 Y505H,Y505H,Y505H,Y505H,Y505H,Y505H YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His,YP_009724390.1:p.Tyr505His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed first in a single tiger (cohort of 5), potential adaptation. McAloose 2020 https://doi.org/10.1128/mBio.02220-20 doi:10.1128/mBio.02220-20 pmid:33051368 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23075 Y505Q YP_009724390.1:p.Tyr505Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23102 S514T NC_045512.2(GU280_gp02):g.1540T>A YP_009724390.1:p.Ser514Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.12 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23108 E516Q NC_045512.2(GU280_gp02):g.1546G>C YP_009724390.1:p.Glu516Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.21 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23115 L518Q NC_045512.2(GU280_gp02):g.1553T>A YP_009724390.1:p.Leu518Gln surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.06 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23120 A520S NC_045512.2(GU280_gp02):g.1558G>T YP_009724390.1:p.Ala520Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness CR3022 (SARS-targeting mAb) cross-reactivity lost ~4x binding against this isolated mutation. Engelhart 2021 https://doi.org/10.1101/2021.04.27.440939 doi:10.1101/2021.04.27.440939 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23148 K529T NC_045512.2(GU280_gp02):g.1586A>C YP_009724390.1:p.Lys529Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) gene expression increase Experimentally, Spike gene expression increased 0.15 fold Starr 2020 https://doi.org/10.1016/j.cell.2020.08.012 doi:10.1016/j.cell.2020.08.012 pmid:32841599 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2(GU280_gp02):g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant raises PIWAS epitope score from 3.6% to 6.2% (improved immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, P681H, Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2(GU280_gp02):g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2(GU280_gp02):g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing statistically significant increased infection rate amongst the cells. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23271 A570D NC_045512.2(GU280_gp02):g.1709C>A YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated that there is very little free energy change (ddG. -0.02 kcal/mol) for this variant (i.e. approx. same stability as wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23373 T604I NC_045512.2(GU280_gp02):g.1811C>T YP_009724390.1:p.Thr604Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection, but also in cell culture without plasma, therefore likely a replication cycle fitness rather than polyclonal immunity escape variant. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation (a.k.a. 'Doug') outside the receptor binding domain, while highly favorable to improved human-human transmission, decreases transduction in naked mole-rat (Heterocephalus glaber) fibroblast and Japanese pipistrelle bat (Pipistrellus abramus) cell cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking The increased transduction with Spike D614G ranged from 1.3- to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2 and from 1.5- to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction. Daniloski 2021 https://doi.org/10.7554/eLife.65365 doi:10.7554/eLife.65365 pmid:33570490 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a lentivirus virus pseudotyped with D614G Spike, sera from vaccinated individuals who received the second dose (9–11 days post-second dose of Pfizer) exhibited a robust neutralizing potential, with a mean NT50 value of 99,000. This was an average of a 2-fold increase, relative to sera drawn from the individuals who received one dose of vaccination—mean NT50 dilution of 51,300. Importantly, a 6-fold increase in mean NT50 dilution was obtained when sera from the first vaccination dose was compared to convalescent sera from cohort with severe disease (NT50 51,000 vs 8,700) 21 to 63 days post-onset. Kuzmina 2021 https://doi.org/10.1016/j.chom.2021.03.008 doi:10.1016/j.chom.2021.03.008 pmid:33789085 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking ~4x more efficient S2 domain cleavage compared to wild type, no change relative to D614G alone in Caco-2 cells, mid-range of three cell line tested (Vero and Calu-3). Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity In four cell lines (including 293T-hACE2 cells), this mutation combination increases infectivity vs D614G alone Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Using a pseudovirus assay and 6 ChAdOx1 vaccinee sera, this NTD mutation conferred a 4.85x drop in neutralization (NT50). Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Pseudotyped D614G virus has reduced neutralization activity vs wild type: 1.2x (37 sera Pfizer median 9 days post 2nd dose, 37 sera Moderna median 18 days post 2nd dose). This was NOT significant by ANOVA. Garcia-Beltran 2021 https://doi.org/10.1016/j.cell.2021.03.013 doi:10.1016/j.cell.2021.03.013 pmid:33743213 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking No change in infectivity (24h) relative to D614G alone in Caco-2 cells, Vero or Calu-3. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure CryoEM shows increased proportion of 'one-up' trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2. Yurkovetskiy 2020 https://doi.org/10.1016/j.cell.2020.09.032 doi:10.1016/j.cell.2020.09.032 pmid:32991842 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 1.0x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Based on pseudotyped virus experiments, D614G may increase infectivity by assembling more functional S protein into the virion. Zhang 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 pmid:33243994 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation from B.1.617.3 did not confer an infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Using ACE2-GFP+Spike-RFP fluorescence assay, this NTD+RBD mutation combination from B.1.617.3 did not affect syncytium formation. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.43x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) transmissibility Using a pseudovirus assay, this NTD mutation combination from B.1.617.3 conferred a nearly two-fold infectivity advantage to the spike particles. Mishra 2021 https://doi.org/10.1101/2021.10.04.463028 doi:10.1101/2021.10.04.463028 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus relative to wild type, no change relative to D614G. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Among S variants tested, the D614G mutant shows the highest cell entry (~3.5x wild type), as supported by structural and binding analyses. Ozono 2020 https://doi.org/10.1038/s41467-021-21118-2 doi:10.1038/s41467-021-21118-2 pmid:33558493 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than wild type (~9-fold). This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. 2020 https://doi.org/10.1038/s41467-020-19808-4 doi:10.1038/s41467-020-19808-4 pmid:33243994 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 pmid:33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to wild type, D614G showed increased infectivity (ie. cold stability) after storage at -20°C for up to 30 days. Huang 2021 https://doi.org/10.1128/msphere.00104-21 doi:10.1128/msphere.00104-21 Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.53x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a slight decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) viral load Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission. Plante 2020 https://doi.org/10.1038/s41586-020-2895-3 doi:10.1038/s41586-020-2895-3 pmid:33106671 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 2.5 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) syncytium formation Slight increase in Vero cell-cell membrane fusion assay under infection with VSV pseudotyped virus. Kim 2021 https://doi.org/10.3390/v13040633 doi:10.3390/v13040633 pmid:33917138 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.35x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.05x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.45x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.97x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) tissue specific neutralization The nasal mucosa of Pfizer vaccinees with time course collection was evaluated against VSV pseudotypes: results (only one nasal swab from different previously infected vacinee neutralizing at weeks 3 and 6 against B.1.1.7 and D614G) suggest that vaccinees probably do not elicit an early humoral response detectable at mucosal surfaces even though sera neutralization was observed. They strengthen the hypothesis that some vaccines may not protect against viral acquisition and infection of the oral–nasal region, but may prevent severe disease associated with viral dissemination in the lower respiratory tract. Planas 2021 https://doi.org/10.1038/s41591-021-01318-5 doi:10.1038/s41591-021-01318-5 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403 D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Negative stain EM shows increased proportion of 'one-up' trimer conformation of Spike proteins on the surface of virions, where the up conformation is presumed to be more likely to bind ACE2. Weissman 2020 https://doi.org/10.1101/2020.07.22.20159905 doi:10.1101/2020.07.22.20159905 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21575 D614G,D614G,D614G,D614G,D614G,D614G,L5F YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.23x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21575 D614G,D614G,D614G,D614G,D614G,D614G,L5F YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21575 D614G,D614G,D614G,D614G,D614G,D614G,L5F YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.1x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21575,21846,22317,22319,22320,23011,23012,23664 D614G,D614G,D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,E484K,A701V YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.526) showed a 1.34x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21575,21846,22317,22319,22320,23011,23012,23664 D614G,D614G,D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,E484K,A701V YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.526) showed a 1.02x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21575,21846,22317,22319,22320,23011,23012,23664 D614G,D614G,D614G,D614G,D614G,D614G,L5F,T95I,D253G,D253G,D253G,E484K,E484K,A701V YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu5Phe,YP_009724390.1:p.Thr95Ile,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.526) showed a 1.78x increase in binding (KD) relative to D614G, even though each variant independently decreases binding. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21600 D614G,D614G,D614G,D614G,D614G,D614G,S13I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.42x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21600 D614G,D614G,D614G,D614G,D614G,D614G,S13I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21600 D614G,D614G,D614G,D614G,D614G,D614G,S13I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21600,22018,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing lineage B.1.429 aka Epsilon) showed a 2.82x increase in binding (KD) relative to D614G, indicating a strong marginal effect for L452R. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21600,22018,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. [Stark contrast to 2.15x increase in binding by convalescent plasma 8 months post infection, presumably via memory B cell affinity maturation against L452R effects] 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21600,22018,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,S13I,W152C,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser13Ile,YP_009724390.1:p.Trp152Cys,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing lineage B.1.429 aka Epsilon) showed a 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, indicating ablated marginal effect from L452R. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614 D614G,D614G,D614G,D614G,D614G,D614G,L18F YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.30x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.28x increase (B.1.351 aka Beta), and 1.14x decrease (P.1 aka Gamma). 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Compare to varied binding in full Spike variant complements for major lineages containing this variant subset: 1.17x increase (B.1.351 aka Beta), and 1.47x decrease (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614 D614G,D614G,D614G,D614G,D614G,D614G,L18F YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.07x decrease in binding (KD) relative to D614G. Compare to increased binding in full Spike variant complements for major lineages containing this variant subset: 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614 D614G,D614G,D614G,D614G,D614G,D614G,L18F YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.66x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Compare to decreased binding in full Spike variant complements for major lineages containing this variant subset: 0.96x (B.1.351 aka Beta), 0.77x (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642 D614G,D614G,D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing P.1 aka Gamma) showed a 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642 D614G,D614G,D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing P.1 aka Gamma) showed a 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.27x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614,21621,21638,21974,22132,22812,22812,23011,23012,23060,23061,23062,23062,23063,23063,23521,23521,23522,23524,23524,23525,23525,24642 D614G,D614G,D614G,D614G,D614G,D614G,L18F,T20N,P26S,D138Y,R190S,K417T,K417T,E484K,E484K,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,T1027I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Thr20Asn,YP_009724390.1:p.Pro26Ser,YP_009724390.1:p.Asp138Tyr,YP_009724390.1:p.Arg190Ser,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing P.1 aka Gamma) showed a 4.24x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614,21801,23060,23061,23062,23062,23063,23063,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23664 D614G,D614G,D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,A701V YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing B.1.351 aka Beta) showed a 1.04x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset, in contrast to the largely positive binding values for each individual mutation that comprises the set. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614,21801,23060,23061,23062,23062,23063,23063,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23664 D614G,D614G,D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,A701V YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.351 aka Beta) showed a 3.56x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21614,21801,23060,23061,23062,23062,23063,23063,22206,22810,22810,22811,22812,22813,22813,22813,23011,23012,23664 D614G,D614G,D614G,D614G,D614G,D614G,L18F,D80A,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,D215G,K417N,K417N,K417N,K417N,K417N,K417N,K417N,E484K,E484K,A701V YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu18Phe,YP_009724390.1:p.Asp80Ala,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asp215Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing B.1.351 aka Beta) showed a 1.28x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. It shows a 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21621 D614G,D614G,D614G,D614G,D614G,D614G,T20N YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.39x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21621 D614G,D614G,D614G,D614G,D614G,D614G,T20N YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.96x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21621 D614G,D614G,D614G,D614G,D614G,D614G,T20N YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr20Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21638 D614G,D614G,D614G,D614G,D614G,D614G,P26S YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21638 D614G,D614G,D614G,D614G,D614G,D614G,P26S YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.23x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21638 D614G,D614G,D614G,D614G,D614G,D614G,P26S YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro26Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.58x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766 D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.14x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766 D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.51x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766 D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.33x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination (representing B.1.1.7 aka Alpha) had 5.43x increased binding relative to D614G alone. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding This variant combination (representing B.1.1.7 aka Alpha) showed a 1.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21763,21764,21761,21761,21761,21761,21762,21762,21762,21763,21765,21766,21766,23060,23061,23062,23062,23063,23063,23271,23604,23604,23709,24506,24914 D614G,D614G,D614G,D614G,D614G,D614G,H69del,H69del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,V70del,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y,A570D,P681H,P681H,T716I,S982A,D1118H YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Ala67_Val70delinsValIle,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.His69_Val70del,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Ala570Asp,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Thr716Ile,YP_009724390.1:p.Ser982Ala,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding This variant combination (representing B.1.1.7 aka Alpha) showed no change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.28x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21801 D614G,D614G,D614G,D614G,D614G,D614G,D80A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant combination showed no change relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21801 D614G,D614G,D614G,D614G,D614G,D614G,D80A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.64x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.35x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21801 D614G,D614G,D614G,D614G,D614G,D614G,D80A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp80Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.11x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21846 D614G,D614G,D614G,D614G,D614G,D614G,T95I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21846 D614G,D614G,D614G,D614G,D614G,D614G,T95I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21846 D614G,D614G,D614G,D614G,D614G,D614G,T95I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr95Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding No change in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21974 D614G,D614G,D614G,D614G,D614G,D614G,D138Y YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21974 D614G,D614G,D614G,D614G,D614G,D614G,D138Y YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.32x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,21974 D614G,D614G,D614G,D614G,D614G,D614G,D138Y YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp138Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.37x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.56x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22018 D614G,D614G,D614G,D614G,D614G,D614G,W152C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.33x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22018 D614G,D614G,D614G,D614G,D614G,D614G,W152C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.15x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22018 D614G,D614G,D614G,D614G,D614G,D614G,W152C YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Trp152Cys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.03x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22132 D614G,D614G,D614G,D614G,D614G,D614G,R190S YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22132 D614G,D614G,D614G,D614G,D614G,D614G,R190S YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.59x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22132 D614G,D614G,D614G,D614G,D614G,D614G,R190S YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Arg190Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.82x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22206 D614G,D614G,D614G,D614G,D614G,D614G,D215G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.19x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22206 D614G,D614G,D614G,D614G,D614G,D614G,D215G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22206 D614G,D614G,D614G,D614G,D614G,D614G,D215G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp215Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.79x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.3x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D614G,D614G,D253G,D253G,D253G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D614G,D614G,D253G,D253G,D253G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.08x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22317,22319,22320 D614G,D614G,D614G,D614G,D614G,D614G,D253G,D253G,D253G YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly,YP_009724390.1:p.Asp253Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22810,22810,22811,22812,22813,22813,22813 D614G,D614G,D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.5x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22810,22810,22811,22812,22813,22813,22813 D614G,D614G,D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22810,22810,22811,22812,22813,22813,22813 D614G,D614G,D614G,D614G,D614G,D614G,K417N,K417N,K417N,K417N,K417N,K417N,K417N YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn,YP_009724390.1:p.Lys417Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.76x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.75x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22812,22812 D614G,D614G,D614G,D614G,D614G,D614G,K417T,K417T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22812,22812 D614G,D614G,D614G,D614G,D614G,D614G,K417T,K417T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.28x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22812,22812 D614G,D614G,D614G,D614G,D614G,D614G,K417T,K417T YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Lys417Thr,YP_009724390.1:p.Lys417Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by convalescent plasma [no cohort details provided] Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy Relative to B.1, Epsilon (B.1.417/429) shows 1.74x-2.35x decrease in neutralization efficiency by 18 vaccinee sera (BNT162b2 and mRNA1273). Wilhelm 2021 https://doi.org/10.1101/2021.08.09.21261704 doi:10.1101/2021.08.09.21261704 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.05x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.16x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 2.15x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,22915,22915,22916,22916,22917,22917 D614G,D614G,D614G,D614G,D614G,D614G,L452R,L452R,L452R,L452R,L452R,L452R YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg,YP_009724390.1:p.Leu452Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.66x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23011,23012 D614G,D614G,D614G,D614G,D614G,D614G,E484K,E484K YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.42x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23011,23012 D614G,D614G,D614G,D614G,D614G,D614G,E484K,E484K YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This variant appears twice in the experiments, with slightly different affinities (both ~1.2x decrease in binding relative to D614G) using flow cytometry and ACE2 ectodomains-Fc portion IgG complex. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23011,23012 D614G,D614G,D614G,D614G,D614G,D614G,E484K,E484K YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Glu484Lys,YP_009724390.1:p.Glu484Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.16x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23060,23061,23062,23062,23063,23063 D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 2.52x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis). Compare to full Spike variant complements for major lineages containing this variant subset: 5.43x (B.1.1.7 aka Alpha), 3.56x (B.1.351 aka Beta), 4.24x (P.1 aka Gamma). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23060,23061,23062,23062,23063,23063 D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.65x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23060,23061,23062,23062,23063,23063 D614G,D614G,D614G,D614G,D614G,D614G,N501Y,N501Y,N501Y,N501Y,N501Y,N501Y YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr,YP_009724390.1:p.Asn501Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.17x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23271 D614G,D614G,D614G,D614G,D614G,D614G,A570D YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.29x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23271 D614G,D614G,D614G,D614G,D614G,D614G,A570D YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.18x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23271 D614G,D614G,D614G,D614G,D614G,D614G,A570D YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala570Asp surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding No significant change in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525 D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.48x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525 D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.21x increase in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23521,23521,23522,23524,23524,23525,23525 D614G,D614G,D614G,D614G,D614G,D614G,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.04x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.09x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23604,23604 D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccine neutralization efficacy No significant change in virus neutralzation by 18 Pfizer two dose vaccinee sera compared to B.1.1.7. [results without including the used mutation A27S likely generalizable, as this is not a lineage defining mutation] Zuckerman 2021 https://doi.org/10.1101/2021.03.25.21253908 doi:10.1101/2021.03.25.21253908 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23604,23604 D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.14x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23604,23604 D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23604,23604 D614G,D614G,D614G,D614G,D614G,D614G,P681H,P681H YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.26x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23664 D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.11x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23664 D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.19x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.1x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23664 D614G,D614G,D614G,D614G,D614G,D614G,A701V YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed essentially no change in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23709 D614G,D614G,D614G,D614G,D614G,D614G,T716I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.12x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23709 D614G,D614G,D614G,D614G,D614G,D614G,T716I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.58x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,23709 D614G,D614G,D614G,D614G,D614G,D614G,T716I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.02x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.47x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24506 D614G,D614G,D614G,D614G,D614G,D614G,S982A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.06x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24506 D614G,D614G,D614G,D614G,D614G,D614G,S982A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 2x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.12x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24506 D614G,D614G,D614G,D614G,D614G,D614G,S982A YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.3x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24642 D614G,D614G,D614G,D614G,D614G,D614G,T1027I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.32x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.22x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24642 D614G,D614G,D614G,D614G,D614G,D614G,T1027I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.56x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24642 D614G,D614G,D614G,D614G,D614G,D614G,T1027I YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.69x decrease in binding (KD) relative to D614G. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24914 D614G,D614G,D614G,D614G,D614G,D614G,D1118H YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma binding 1.96x increase in Spike binding (relative to D614G alone) by 5 plasma collected 8 months post-symptom-onset. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24914 D614G,D614G,D614G,D614G,D614G,D614G,D1118H YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity Using flow cytometry and ACE2 ectodomains-Fc portion IgG complex, this variant showed a 1.23x increase in binding (KD) relative to D614G, mostly due to decreased in 'off-rate' a.k.a. dissociation rate (Kdis). Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23399,23401,23401,23402,23403,23403,24914 D614G,D614G,D614G,D614G,D614G,D614G,D1118H YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) vaccinee plasma binding 1.09x increase in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in previously non-seroconverted subjects. 1.08x decrease in Spike binding (relative to D614G alone) by 5 plasma collected 3 weeks after one dose of Pfizer/BioNtech BNT162b2 vaccine in post-infection vaccinees. Gong 2021 https://doi.org/10.1101/2021.08.04.455140 doi:10.1101/2021.08.04.455140 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23429 A623T NC_045512.2(GU280_gp02):g.1867G>A YP_009724390.1:p.Ala623Thr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23521,23522,23524,23524,23525,23525 H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation in the N terminal domain appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23521,23522,23524,23524,23525,23525 H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Six minks were intranasally infected with WA1 isolate, all developed this mutation during infection. Esclera 2021 https://doi.org/10.1101/2021.08.05.455290 doi:10.1101/2021.08.05.455290 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23521,23522,23524,23524,23525,23525 H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain increases the virus transduction rate in tree shrew (Tupaia belangeri), (as it does in humans) according to pseudotyped VSV experiments. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23521,23521,23522,23524,23524,23525,23525 H655Y,H655Y,H655Y,H655Y,H655Y,H655Y,H655Y YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr,YP_009724390.1:p.His655Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 0.87 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23587,23587,23587 Q675H,Q675H,Q675H ,NC_045512.2(GU280_gp02):g.2025G>C,NC_045512.2(GU280_gp02):g.2025G>T YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His,YP_009724390.1:p.Gln675His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly enhanced the ability of the pseudotyped VSV to infect fat-tailed gerbil (Pachyuromys duprasi) kidney cell cultures, with a transduction rate of 13.4%, close to the 15.7% in epithelial-like human Huh-7 cells while starting from a significantly lower wildtype (Wuhan-Hu-1 Spike VSVdeltaG psuedotype) rate. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23599,23599,23604,23604 P681R,P681R,P681R,P681R YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). [Inference from similar positively charged substitution P681H actually described in the work] 2021 https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23599,23599,23604,23604 P681R,P681R,P681R,P681R YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. [PG: Inferred by conservative AA substitution of described P681H] Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23599,23599,23604,23604,23399,23401,23401,23402,23403,23403 P681R,P681R,P681R,P681R,D614G,D614G,D614G,D614G,D614G,D614G YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Pro681Arg,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly,YP_009724390.1:p.Asp614Gly surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Quantification of the band intensities showed that the P681R mutation, which lies near the proteolytic processing site, caused a small increase in proteolytic processing as measured by a 2-fold decrease in the ratio of S/S2. Tada 2021 https://doi.org/10.1101/2021.05.14.444076 doi:10.1101/2021.05.14.444076 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H NC_045512.2(GU280_gp02):g.2042C>A, YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) pharmaceutical effectiveness This individual mutation found in the epitope from Sotrovimab causes a 0.9x reduction in neutralization efficacy using a VSV model on Vero E6 cells. Cathcart 2021 https://doi.org/10.1101/2021.03.09.434607v9 doi:10.1101/2021.03.09.434607v9 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H NC_045512.2(GU280_gp02):g.2042C>A, YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing NO statistically significant infection rate change amongst the cells, suggesting that furin cleavage typically used for cell entry is not affected by this change one amino acid upstream of the RXXR recognition pattern. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H NC_045512.2(GU280_gp02):g.2042C>A, YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking While the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC). Lubinski 2021 https://doi.org/10.1101/2021.04.06.438731 doi:10.1101/2021.04.06.438731 pmid:33851153 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H NC_045512.2(GU280_gp02):g.2042C>A, YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Ablates Class 3 N-terminal domain targeting antibody COV2-2489, diminishes COV2-2676. Chen 2021 https://doi.org/10.1038/s41591-021-01294-w doi:10.1038/s41591-021-01294-w pmid:33664494 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H NC_045512.2(GU280_gp02):g.2042C>A, YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects This variant is adjacent to the Spike protein furin cleavage site (cleavage of S into S1 and S2 subunits is required for viral membrane fusion and subsequent entry into host cells), a site shown to be highly immunogenic. Johnson 2020 https://doi.org/10.1101/2020.08.26.268854 doi:10.1101/2020.08.26.268854 pmid:32869021 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H NC_045512.2(GU280_gp02):g.2042C>A, YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure The Ratio of S2 (processed Spike) to full length Spike is higher for this mutation, due to a drop in the full length Spike measured, suggesting that this mutation compensates for decreased Spike production by improved proteolytic processing. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H NC_045512.2(GU280_gp02):g.2042C>A, YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking In the absence of N501Y, this Alpha lineage change in the furin clevage site did NOT show significant increase in infectivity relative to wild type, as determined by modelling the infectivity of each Spike mutation independently in a competitive infection model of hamsters. Liu 2021 https://doi.org/10.1101/2021.03.08.434499 doi:10.1101/2021.03.08.434499 pmid:33758836 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H NC_045512.2(GU280_gp02):g.2042C>A, YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Wildtype elicits immune response, COVID-19 cohort epitope score > 99th percentile of the 497 pre-pandemic controls, mutant drops PIWAS epitope score from 7.8% to 1.2% (significantly poorer immune recognition) Together with other B1.1.7 lineage mutational changes (Spike: Y144del,N501Y, A570D Nucleoprotein: D3L, S235F) resulted in only 2 of 579 individuals (0.3% of the population) having a dramatic reduction in PIWAS antigen scores, which reflects the peak epitope signal along the entire antigen. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23604,23604 P681H,P681H NC_045512.2(GU280_gp02):g.2042C>A, YP_009724390.1:p.Pro681His,YP_009724390.1:p.Pro681His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking This mutation in the first base of the furin clevage site maintains the RXXR recognition motif, and is presumed to enhance cleavage based on the removal of a proline-directed phosphotase recognition site at S680. In a homologuous site in Infectious Bronchitis Virus (IBV, Gammacoronaviruses), abolition of S680 phosphorylation improves furin cleavage (and presumably cell entry). 2021 https://www.researchgate.net/publication/348943694_The_mutation_P681H_in_the_B117_variant_of_SARS-CoV-2_probably_enhances_viral_entry_and_replication False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23664 A701V NC_045512.2(GU280_gp02):g.2102C>T YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.351 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, suggesting that this mutation does not contributing to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23664 A701V NC_045512.2(GU280_gp02):g.2102C>T YP_009724390.1:p.Ala701Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is -0.33 kcal/mol (i.e. destabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2(GU280_gp02):g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain showed a decreased capacity to transduce PK-15 (pig kidney, Sus scrofa) and PaKi (black flying fox kidney, Pteropus alecto) cell line cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2(GU280_gp02):g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. T716I was expressed at significantly lower level, accounting for the decreased infectivity of this spike protein. This property may be specific to spike protein biosynthesis in 293T cells and is not likely to reflect the situation in vivo given the reported increase in infectivity of the B.1.1.7 virus. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2(GU280_gp02):g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events Observed first in a single tiger (cohort of 5), potential adaptation. McAloose 2020 https://doi.org/10.1128/mBio.02220-20 doi:10.1128/mBio.02220-20 pmid:33051368 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23709 T716I NC_045512.2(GU280_gp02):g.2147C>T YP_009724390.1:p.Thr716Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not in a major wildtype epitope, mutant increases PIWAS epitope score from 0.69% to 2.3% Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23897 Q779K NC_045512.2(GU280_gp02):g.2335C>A YP_009724390.1:p.Gln779Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) monoclonal antibody serial passage escape Escape variant 20% appearance in 2 passages against Regeneron monoclonal antibody RGN10989 @ 50ug/mL Baum 2020 https://doi.org/10.1126/science.abd0831 doi:10.1126/science.abd0831 pmid:32540904 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 23948 D796H NC_045512.2(GU280_gp02):g.2386G>C YP_009724390.1:p.Asp796His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Fatal COVID-19 complications in immunocomprimised patient after immune escape from convalescent plasma Kemp 2020 https://doi.org/10.1101/2020.12.05.20241927 doi:10.1101/2020.12.05.20241927 pmid:33398302 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24000 S813I NC_045512.2(GU280_gp02):g.2438G>T YP_009724390.1:p.Ser813Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2(GU280_gp02):g.2492C>T YP_009724390.1:p.Ala831Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Resistent to neutralizing mAb B38 Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2(GU280_gp02):g.2492C>T YP_009724390.1:p.Ala831Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Resistant to a pool of 10 convalescent sera (but less than 4x, a typical threshold for definition of escape) Li 2020 https://doi.org/10.1016/j.cell.2020.07.012 doi:10.1016/j.cell.2020.07.012 pmid:32730807 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24054 A831V NC_045512.2(GU280_gp02):g.2492C>T YP_009724390.1:p.Ala831Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant shown in vitro to not have major defects or enhancement of cell surface protein trafficking (i.e. Spike cleavage or fusion required for cell entry) Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 pmid:33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24077 D839N NC_045512.2(GU280_gp02):g.2515G>A YP_009724390.1:p.Asp839Asn surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry. Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 pmid:33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24077 D839Y NC_045512.2(GU280_gp02):g.2515G>T YP_009724390.1:p.Asp839Tyr surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant near the internal fusion peptide shown in vitro to reduce Spike subunit fusion required for cell entry. Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 pmid:33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24130 N856K NC_045512.2(GU280_gp02):g.2568C>A YP_009724390.1:p.Asn856Lys surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) branch specific selection pressure Using the Contrast-FEL method, this mutation is differentially selected along the B.1.1.529 (WHO VOC Omicron) branch. Lucaci 2021 https://observablehq.com/@aglucaci/sc2-omicron Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24170 I870V NC_045512.2(GU280_gp02):g.2608A>G YP_009724390.1:p.Ile870Val surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) immunosuppression variant emergence Appeared (day 75) and persisted in chronic (152 day) SARS-CoV-2 infection of immunocompromised patient with severe antiphospholipid syndrome Appeared at same time as T478K,S494P but listed separately due to distance and different domains affected in the Spike (i.e. putatively an independent mutation from a functional standpoint since the former are from S1, the latter from S2). Choi 2020 https://doi.org/10.1056/NEJMc2031364 doi:10.1056/NEJMc2031364 pmid:33176080 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24377,24378,24378 S939F,S939F,S939F NC_045512.2(GU280_gp02):g.2816C>T,NC_045512.2(GU280_gp02):g.2816C>T, YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe,YP_009724390.1:p.Ser939Phe surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) anthropozoonotic events This mutation outside the receptor binding domain significantly reduced the tropism of SARS-CoV-2 to MfuKi (eastern bent-wing bat kidney cell, Miniopterus fuliginosus) cell cultures using a pseudotyped VSV assay. Li 2023 https://doi.org/10.1038/s41396-023-01368-2 doi:10.1038/s41396-023-01368-2 pmid:36690780 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2(GU280_gp02):g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape The neutralizing activity of 6/20 convalescent sera was significantly lower against this single variant pseudotyped virus model, showing similar patterns to the pseudotyped virus model of B.1.1.7. Wang 2021 https://doi.org/10.1038/s41586-021-03398-2 doi:10.1038/s41586-021-03398-2 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2(GU280_gp02):g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) ACE2 receptor binding affinity This mutation causes major decrease in binding affinity vs. wild type as measured by IC50 vs pseudotyped lentivirus. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2(GU280_gp02):g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2(GU280_gp02):g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) environmental condition stability Relative to D614G, this mutation demonstrated significant increase in infectivity (i.e. heat stability) after incubation at 50C after 30 minutes or 1 hour Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24506 S982A NC_045512.2(GU280_gp02):g.2944T>G YP_009724390.1:p.Ser982Ala surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing major (70%) increase in infection rate amongst the cells, hence this individual variant is likely to significantly contribute to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24642 T1027I NC_045512.2(GU280_gp02):g.3080C>T YP_009724390.1:p.Thr1027Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) virion structure Estimated free energy change (ddG) for this variant is 1.51 kcal/mol (i.e. stabilizing relative to wild type) Spratt 2021 https://doi.org/10.1101/2021.03.24.436850 doi:10.1101/2021.03.24.436850 pmid:33791700 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2(GU280_gp02):g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) antibody epitope effects Not in a major wildtype epitope, mutant has no significant effect on PIWAS epitope score Found in B.1.1.7 lineage, but assumed to not pay a major role in antigenicity. Haynes 2021 https://doi.org/10.1101/2021.01.06.20248960 doi:10.1101/2021.01.06.20248960 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2(GU280_gp02):g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion Mutation is predicted to lose the T cell epitope for people carrying DRB1*0301 and DRB1*0401, but not for example in those who are DRB1*0701 or DRB1*1501 who would be predicted to show an enhanced response. This is also observed in a study of 26 each post-infection and post first dose HCWs. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 pmid:33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2(GU280_gp02):g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this individual mutation from B.1.1.7 was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing mild decrease in infection rate amongst the cells, hence this individual variant is unlikely to contribute to cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 24914 D1118H NC_045512.2(GU280_gp02):g.3352G>C YP_009724390.1:p.Asp1118His surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD4 positive t-cells in people with HLA class 2. Reynolds 2021 https://doi.org/10.1126/science.abh1282 doi:10.1126/science.abh1282 pmid:33931567 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25045,25046,25046 P1162S,P1162S,P1162S YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser,YP_009724390.1:p.Pro1162Ser surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) convalescent plasma escape Escape mutant found after in passage in plasma pool of 26 convalescents obtained mean 1.3 months post infection. Schmidt 2021 https://doi.org/10.1101/2021.08.06.455491 doi:10.1101/2021.08.06.455491 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25249,25249,25249 M1229I,M1229I,M1229I NC_045512.2(GU280_gp02):g.3687G>C,NC_045512.2(GU280_gp02):g.3687G>T,NC_045512.2(GU280_gp02):g.3687G>A YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile,YP_009724390.1:p.Met1229Ile surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Lentiviral pseudotyped with this mutation from Mink Cluster 5 lineage, was tested on ACE2.293T cells. Luciferase activity was measured two days postinfection, showing slight decrease in infection rate amongst the cells, suggesting that this variant does not contributing to human cell entry fitness. Tada 2021 https://doi.org/10.1101/2021.02.05.430003 doi:10.1101/2021.02.05.430003 pmid:33564768 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25350 P1263L NC_045512.2(GU280_gp02):g.3788C>T YP_009724390.1:p.Pro1263Leu surface glycoprotein gene (SARS-CoV-2) s gene (SARS-CoV-2) surface glycoprotein (SARS-CoV-2) S protein (SARS-CoV-2) trafficking Circulating variant in the cytoplasmic tail, shown in vitro to increase Spike subunit fusion required for cell entry Barrett 2021 https://doi.org/10.1101/2021.01.24.428007 doi:10.1101/2021.01.24.428007 pmid:33532777 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 25855 D155Y NC_045512.2(GU280_gp03):g.463G>T YP_009724391.1:p.Asp155Tyr open reading frame 3a gene (SARS-CoV-2) orf3a gene (SARS-CoV-2) open reading frame 3a protein (SARS-CoV-2) Orf3a protein (SARS-CoV-2) caveolin binding In silico, this mutation is the only one weakening ORF3a's binding affinity for caveolin-1 (essential for entry and endomembrane trafficking of SARS-CoV-2). This mutation is a widespread homoplasy in 20A and 20B lineages. Gupta 2021 https://doi.org/10.1101/2021.03.26.437194 doi:10.1101/2021.03.26.437194 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26029 Q213K NC_045512.2(GU280_gp03):g.637C>A YP_009724391.1:p.Gln213Lys open reading frame 3a gene (SARS-CoV-2) orf3a gene (SARS-CoV-2) open reading frame 3a protein (SARS-CoV-2) Orf3a protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*01:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26029 Q213K NC_045512.2(GU280_gp03):g.637C>A YP_009724391.1:p.Gln213Lys open reading frame 3a gene (SARS-CoV-2) orf3a gene (SARS-CoV-2) open reading frame 3a protein (SARS-CoV-2) Orf3a protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to A*01:01-restricted CD8+ ORF3a epitope, which is otherwise 'consistently dominant and of high magnitude'. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26256 F4F NC_045512.2(GU280_gp04):g.12C>T YP_009724392.1:p.Phe4Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26268,26268,26269,26270 T9I,T9I,T9I,T9I ,NC_045512.2(GU280_gp04):g.26C>T,NC_045512.2(GU280_gp04):g.26C>T,NC_045512.2(GU280_gp04):g.26C>T YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26268,26268,26269,26270 T9I,T9I,T9I,T9I ,NC_045512.2(GU280_gp04):g.26C>T,NC_045512.2(GU280_gp04):g.26C>T,NC_045512.2(GU280_gp04):g.26C>T YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile,YP_009724392.1:p.Thr9Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~300 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26295,26296 L18I,L18I ,NC_045512.2(GU280_gp04):g.52C>A YP_009724392.1:p.Leu18Ile,YP_009724392.1:p.Leu18Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (47x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26299 L19F NC_045512.2(GU280_gp04):g.55C>T YP_009724392.1:p.Leu19Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26312 F23C NC_045512.2(GU280_gp04):g.68T>G YP_009724392.1:p.Phe23Cys envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~8.8 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26314 V24M NC_045512.2(GU280_gp04):g.70G>A YP_009724392.1:p.Val24Met envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26319 V25V NC_045512.2(GU280_gp04):g.75A>G YP_009724392.1:p.Val25Val envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (45x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26333 T30I NC_045512.2(GU280_gp04):g.89C>T YP_009724392.1:p.Thr30Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26353 L37F NC_045512.2(GU280_gp04):g.109C>T YP_009724392.1:p.Leu37Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26395 L51I NC_045512.2(GU280_gp04):g.151C>A YP_009724392.1:p.Leu51Ile envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (47x overrepresentation vs expected count of ~24 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26416 V58L NC_045512.2(GU280_gp04):g.172G>C YP_009724392.1:p.Val58Leu envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26428 V62F NC_045512.2(GU280_gp04):g.184G>T YP_009724392.1:p.Val62Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (18x overrepresentation vs expected count of ~333 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26442 N66K NC_045512.2(GU280_gp04):g.198T>G YP_009724392.1:p.Asn66Lys envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~23 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26447 S68F NC_045512.2(GU280_gp04):g.203C>T YP_009724392.1:p.Ser68Phe envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26447 S68C NC_045512.2(GU280_gp04):g.203C>G YP_009724392.1:p.Ser68Cys envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (58x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26456 P71R NC_045512.2(GU280_gp04):g.212C>G YP_009724392.1:p.Pro71Arg envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26466,26467 V75L,V75L ,NC_045512.2(GU280_gp04):g.223G>C YP_009724392.1:p.Val75Leu,YP_009724392.1:p.Val75Leu envelope gene (SARS-CoV-2) e gene (SARS-CoV-2) envelope protein (SARS-CoV-2) E protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (3762.7x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526 A2S NC_045512.2(GU280_gp05):g.4G>T YP_009724393.1:p.Ala2Ser membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) immunosuppression variant emergence Emergent as 16% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing. Avanzato 2020 https://doi.org/10.1016/j.cell.2020.10.049 doi:10.1016/j.cell.2020.10.049 pmid:33248470 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526 A2S NC_045512.2(GU280_gp05):g.4G>T YP_009724393.1:p.Ala2Ser membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (38x overrepresentation vs expected count of ~334 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26526,26527,26528,26528,26529 D3H,D3H,D3H,D3H,D3H YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His,YP_009724393.1:p.Asp3His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (227x overrepresentation vs expected count of ~14 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26528,26528,26528 A2A,A2A,A2A NC_045512.2(GU280_gp05):g.6A>C,NC_045512.2(GU280_gp05):g.6A>G,NC_045512.2(GU280_gp05):g.6A>T YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala,YP_009724393.1:p.Ala2Ala membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (25x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26530 D3G NC_045512.2(GU280_gp05):g.8A>G YP_009724393.1:p.Asp3Gly membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (31x overrepresentation vs expected count of ~53 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26542 T7I NC_045512.2(GU280_gp05):g.20C>T YP_009724393.1:p.Thr7Ile membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 pmid:33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26546 I8I NC_045512.2(GU280_gp05):g.24T>C YP_009724393.1:p.Ile8Ile membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~80 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26573,26573,26576,26576,26577,26577 Q19E,Q19E,Q19E,Q19E,Q19E,Q19E YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu,YP_009724393.1:p.Gln19Glu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~8 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26620 C33S NC_045512.2(GU280_gp05):g.98G>C YP_009724393.1:p.Cys33Ser membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~32 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26645 N41N NC_045512.2(GU280_gp05):g.123C>T YP_009724393.1:p.Asn41Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (19x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26681 F53F NC_045512.2(GU280_gp05):g.159C>T YP_009724393.1:p.Phe53Phe membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (163x overrepresentation vs expected count of ~567 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26730 V70L NC_045512.2(GU280_gp05):g.208G>C YP_009724393.1:p.Val70Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26748 I76L NC_045512.2(GU280_gp05):g.226A>C YP_009724393.1:p.Ile76Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~9 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26748 I76V NC_045512.2(GU280_gp05):g.226A>G YP_009724393.1:p.Ile76Val membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26749 I76T NC_045512.2(GU280_gp05):g.227T>C YP_009724393.1:p.Ile76Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (19x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26767 I82T NC_045512.2(GU280_gp05):g.245T>C YP_009724393.1:p.Ile82Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (67x overrepresentation vs expected count of ~42 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26767 I82T NC_045512.2(GU280_gp05):g.245T>C YP_009724393.1:p.Ile82Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) homoplasy This mutation presents mainly within the B.1 (44.0%) and B.1.525 (38.1%) lineages. Currently, 99.7% of the B.1.525 lineage isolates carry the M:I82T mutation. While this mutation is scattered across multiple phylogenetic clades, most cases cluster in two recent clades, suggesting a likely selective advantage in certain haplotype backgrounds. Shen 2021 https://doi.org/10.1080/22221751.2021.1922097 doi:10.1080/22221751.2021.1922097 pmid:33896413 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26801,26801,26801 L93L,L93L,L93L NC_045512.2(GU280_gp05):g.279C>T,NC_045512.2(GU280_gp05):g.279C>A,NC_045512.2(GU280_gp05):g.279C>G YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu,YP_009724393.1:p.Leu93Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~628 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26855,26858 F112F,F112F NC_045512.2(GU280_gp05):g.336C>T,NC_045512.2(GU280_gp05):g.336C>T YP_009724393.1:p.Phe112Phe,YP_009724393.1:p.Phe112Phe membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~463 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26861 N113N NC_045512.2(GU280_gp05):g.339T>C YP_009724393.1:p.Asn113Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (57x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26873 N117N NC_045512.2(GU280_gp05):g.351C>T YP_009724393.1:p.Asn117Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26882,26882,26882 L120L,L120L,L120L NC_045512.2(GU280_gp05):g.360C>G,NC_045512.2(GU280_gp05):g.360C>T,NC_045512.2(GU280_gp05):g.360C>A YP_009724393.1:p.Leu120Leu,YP_009724393.1:p.Leu120Leu,YP_009724393.1:p.Leu120Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26894,26894 L124L,L124L NC_045512.2(GU280_gp05):g.372C>T,NC_045512.2(GU280_gp05):g.372C>G YP_009724393.1:p.Leu124Leu,YP_009724393.1:p.Leu124Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~622 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26895 H125Y NC_045512.2(GU280_gp05):g.373C>T YP_009724393.1:p.His125Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (22x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26895 H125Y NC_045512.2(GU280_gp05):g.373C>T YP_009724393.1:p.His125Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) homoplasy In experimental models of SARA_CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26907,26909,26909 L129L,L129L,L129L NC_045512.2(GU280_gp05):g.385C>T,NC_045512.2(GU280_gp05):g.387G>T,NC_045512.2(GU280_gp05):g.387G>A YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu,YP_009724393.1:p.Leu129Leu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~12 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26927 E135E NC_045512.2(GU280_gp05):g.405A>G YP_009724393.1:p.Glu135Glu membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (232x overrepresentation vs expected count of ~73 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26951,26951,26951 V143V,V143V,V143V NC_045512.2(GU280_gp05):g.429G>A,NC_045512.2(GU280_gp05):g.429G>T,NC_045512.2(GU280_gp05):g.429G>C YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val,YP_009724393.1:p.Val143Val membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~508 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26966 H148H NC_045512.2(GU280_gp05):g.444T>C YP_009724393.1:p.His148His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26972 R150R NC_045512.2(GU280_gp05):g.450T>C YP_009724393.1:p.Arg150Arg membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~89 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26985 H155N NC_045512.2(GU280_gp05):g.463C>A YP_009724393.1:p.His155Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (20x overrepresentation vs expected count of ~39 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 26987 H155H NC_045512.2(GU280_gp05):g.465T>C YP_009724393.1:p.His155His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27021 E167Q NC_045512.2(GU280_gp05):g.499G>C YP_009724393.1:p.Glu167Gln membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (133x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27035,27038 T172T,T172T NC_045512.2(GU280_gp05):g.516A>G,NC_045512.2(GU280_gp05):g.516A>G YP_009724393.1:p.Thr172Thr,YP_009724393.1:p.Thr172Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~102 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27059 Y179Y NC_045512.2(GU280_gp05):g.537C>T YP_009724393.1:p.Tyr179Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27112 S197T NC_045512.2(GU280_gp05):g.590G>C YP_009724393.1:p.Ser197Thr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (18x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27134 Y204Y NC_045512.2(GU280_gp05):g.612T>C YP_009724393.1:p.Tyr204Tyr membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (29x overrepresentation vs expected count of ~66 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27143 N207N NC_045512.2(GU280_gp05):g.621C>T YP_009724393.1:p.Asn207Asn membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (10x overrepresentation vs expected count of ~572 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 27147 D209H NC_045512.2(GU280_gp05):g.625G>C YP_009724393.1:p.Asp209His membrane glycoprotein gene (SARS-CoV-2) m gene (SARS-CoV-2) membrane glycoprotein (SARS-CoV-2) M protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (81x overrepresentation vs expected count of ~18 in public genome datasets), analysis as of 2023-05-11 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28144 L84S NC_045512.2(GU280_gp09):g.251T>C YP_009724396.1:p.Leu84Ser open reading frame 8 gene (SARS-CoV-2) orf8 gene (SARS-CoV-2) open reading frame 8 protein (SARS-CoV-2) Orf8 protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 pmid:33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28306,28306,28307,28308,28308,28309,28309,28310,28310,28311,28311 P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28306,28306,28307,28308,28308,28309,28309,28310,28310,28311,28311 P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L,P13L YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu,YP_009724397.2:p.Pro13Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13). de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28310 P13S NC_045512.2(GU280_gp10):g.37C>T YP_009724397.2:p.Pro13Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*27:05. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28310 P13S NC_045512.2(GU280_gp10):g.37C>T YP_009724397.2:p.Pro13Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to B*27:05-restricted CD8+ N epitope QRNAPRITF 1-17(2,13). de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28655,28877,28881 D128H,G204R,G204R YP_009724397.2:p.Asp128His,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) reinfection Reinfection in an October 2020 of a 40yo female Brazilian HCW, no hospitalization required in first or second infection. Poor overall genome quality. Genome also has one Spike mutation that would become a defining mutation in lineage P.2, S:p.V1176F Amorim 2021 https://doi.org/10.3201/eid2706.210558 doi:10.3201/eid2706.210558 pmid:33871331 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28769 T166A NC_045512.2(GU280_gp10):g.496A>G YP_009724397.2:p.Thr166Ala nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) variant linear antibody epitope effects Confers a significant PIWAS value decrease (reduced antigenicity) Haynes 2020 https://doi.org/10.1101/2020.11.23.20235002 doi:10.1101/2020.11.23.20235002 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28853 S194T NC_045512.2(GU280_gp10):g.580T>A YP_009724397.2:p.Ser194Thr nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) anthropozoonotic events Mouse-adapted SARS-CoV-2 mutations after 11 serial passages in various immunocompromised mice strains. Rathnasinghe 2021 https://doi.org/10.1101/2021.01.19.21249592 doi:10.1101/2021.01.19.21249592 pmid:33501468 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28854 S194L NC_045512.2(GU280_gp10):g.581C>T YP_009724397.2:p.Ser194Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) homoplasy Mutation with a population frequency of 30% in a Mexican dataset, primarily of lineage 20B, but also present in a substantial number of 20A lineage sequences, suggesting convergent evolution. Barona-Gomez 2021 https://doi.org/10.1101/2021.05.18.21256128 doi:10.1101/2021.05.18.21256128 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28854 S194L NC_045512.2(GU280_gp10):g.581C>T YP_009724397.2:p.Ser194Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) outcome hazard ratio In March 2021 this variant had an allele frequency of 47.62 and 7.25% in deceased patients, compared to 35.16 and 3.20% of the same variant in recovered patients, from the Gujarat and global datasets. Joshi 2021 https://doi.org/10.3389/fgene.2021.586569 doi:10.3389/fgene.2021.586569 pmid:33815459 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28869 P199L NC_045512.2(GU280_gp10):g.596C>T YP_009724397.2:p.Pro199Leu nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021 https://doi.org/10.1101/2021.08.05.455082 doi:10.1101/2021.08.05.455082 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28877,28881 G204R,G204R YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) posttranslational modifications This variant, caused by three consecutive SNPs, consistently shows a neighbouring serine 206 (S206) site is highly phosphorylated in the mutant N protein via mass spectrometry. Mourier 2021 https://doi.org/10.1101/2021.05.06.21256706 doi:10.1101/2021.05.06.21256706 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28877,28881 G204R,G204R YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) subgenomic RNA expression This variant, likely arisen by homologous recombination from the core sequence (CS) of the leader transcription-regulating sequence (TRS), generate a novel sub-genomic RNA transcript for the C-terminal dimerization domain. It may also have increased expression of sub-genomic RNA from other open reading frames, based on public data analysis. Leary 2021 https://doi.org/10.1101/2020.04.10.029454 doi:10.1101/2020.04.10.029454 pmid:33880475 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28877,28881 G204R,G204R YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) subgenomic RNA expression This variant shows a significant increase in viral load compared to wild type, but not relative to D614G viruses without the variant in circulating viruses in the Spring of 2020 in Saudia Arabia. Mourier 2021 https://doi.org/10.1101/2021.05.06.21256706 doi:10.1101/2021.05.06.21256706 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28877,28881 G204R,G204R YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) gene expression increase By Western blot, a statistically significant 2x increase in N protein expression in packaging cells was observed using mutant novel virus-like-particles. This did not correlate with luciferase activity (which was not statistically different from D614G wild type). Syed 2021 https://doi.org/10.1101/2021.08.05.455082 doi:10.1101/2021.08.05.455082 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28877,28881,29148 G204R,G204R,I292T YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Gly204Arg,YP_009724397.2:p.Ile292Thr nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) reinfection Reinfection in a September 2020 of a 61yo female Brazilian HCW, no hospitalization required in first or second infection. Genome also has one Spike mutation of unknown significance, S:p.Q675H Amorim 2021 https://doi.org/10.3201/eid2706.210558 doi:10.3201/eid2706.210558 pmid:33871331 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28879 S202R NC_045512.2(GU280_gp10):g.606T>G YP_009724397.2:p.Ser202Arg nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows major increase in RNA content with this mutation, suggesting that it improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021 https://doi.org/10.1101/2021.08.05.455082 doi:10.1101/2021.08.05.455082 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 28881 R203M NC_045512.2(GU280_gp10):g.608G>T YP_009724397.2:p.Arg203Met nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) RNA binding Northern blot analysis of novel mutant virus-like-particles (VLPs) shows most increase in RNA content of any N mutation tested, suggesting that this mutation improves virus particle production (requisite RNA packaging signal binding site in nsp15/16 boundary is included in the VLP). Syed 2021 https://doi.org/10.1101/2021.08.05.455082 doi:10.1101/2021.08.05.455082 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29239,29239 M322I,M322I NC_045512.2(GU280_gp10):g.966G>T,NC_045512.2(GU280_gp10):g.966G>A YP_009724397.2:p.Met322Ile,YP_009724397.2:p.Met322Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. Agerer 2021 https://doi.org/10.1126/sciimmunol.abg6461 doi:10.1126/sciimmunol.abg6461 pmid:33664060 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29247 T325I NC_045512.2(GU280_gp10):g.974C>T YP_009724397.2:p.Thr325Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes partial loss of T cell line responsiveness and CTL killing ability by B*40:01-restricted CD8+ N epitope MEVTPSGTWL 322-331. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29247 T325I NC_045512.2(GU280_gp10):g.974C>T YP_009724397.2:p.Thr325Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29266 L331F NC_045512.2(GU280_gp10):g.993G>T YP_009724397.2:p.Leu331Phe nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type B*40:01. Agerer 2021 https://doi.org/10.1126/sciimmunol.abg6461 doi:10.1126/sciimmunol.abg6461 pmid:33664060 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2(GU280_gp10):g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is 'consistently dominant and of high magnitude'. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2(GU280_gp10):g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2(GU280_gp10):g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29358 T362I NC_045512.2(GU280_gp10):g.1085C>T YP_009724397.2:p.Thr362Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2(GU280_gp10):g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*68:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2(GU280_gp10):g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*03:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2(GU280_gp10):g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion This mutation causes reduced recognition by CD8 positive t-cells in people with HLA type A*11:01. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29366 P365S NC_045512.2(GU280_gp10):g.1093C>T YP_009724397.2:p.Pro365Ser nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) T cell evasion Variant causes complete loss of T cell line responsiveness to A*03:01/A*11:01-restricted CD8+ N epitope KTFPPTEPK 361-369(2,8,10,20), which otherwise is 'consistently dominant and of high magnitude'. de Silva 2021 https://doi.org/10.1101/2021.04.08.438904 doi:10.1101/2021.04.08.438904 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 29407,29407,29409 T379I,T379I,T379I ,NC_045512.2(GU280_gp10):g.1136C>T,NC_045512.2(GU280_gp10):g.1136C>T YP_009724397.2:p.Thr379Ile,YP_009724397.2:p.Thr379Ile,YP_009724397.2:p.Thr379Ile nucleocapsid phosphoprotein gene (SARS-CoV-2) n gene (SARS-CoV-2) nucleocapsid phosphoprotein (SARS-CoV-2) N protein (SARS-CoV-2) homoplasy In experimental models of SARS-CoV-2 mutational evolution (without immune pressure), this mutation appears convergent. Borges 2021 https://doi.org/10.1101/2021.05.19.444774 doi:10.1101/2021.05.19.444774 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 335,335 R24C,R24C ,NC_045512.2(GU280_gp01):g.70C>T YP_009724389.1:p.Arg24Cys,YP_009724389.1:p.Arg24Cys open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (25x overrepresentation vs expected count of 514 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 347 V28I NC_045512.2(GU280_gp01):g.82G>A YP_009724389.1:p.Val28Ile open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (30x overrepresentation vs expected count of 143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 383 S40P NC_045512.2(GU280_gp01):g.118T>C YP_009724389.1:p.Ser40Pro open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (16x overrepresentation vs expected count of ~58 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 396 Q44L NC_045512.2(GU280_gp01):g.131A>T YP_009724389.1:p.Gln44Leu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (11x overrepresentation vs expected count of ~19 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 443 V60I NC_045512.2(GU280_gp01):g.178G>A YP_009724389.1:p.Val60Ile open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 489 D75G NC_045512.2(GU280_gp01):g.224A>G YP_009724389.1:p.Asp75Gly open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 490,490 D75E,D75E NC_045512.2(GU280_gp01):g.225T>G,NC_045512.2(GU280_gp01):g.225T>A YP_009724389.1:p.Asp75Glu,YP_009724389.1:p.Asp75Glu open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (15x overrepresentation vs expected count of ~20 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) immunosuppression variant emergence Emergent as 22% variant by day 70 post-infection of female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Variant became 100% in day 70 culture. Variant disappeared after convalescent plasma treatment (day 71) in subsequent patient sample sequencing. Avanzato 2020 https://doi.org/10.1016/j.cell.2020.10.049 doi:10.1016/j.cell.2020.10.049 pmid:33248470 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) IFN activity Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 500-523) was tested in vitro for IFN response. Lin 2021 https://doi.org/10.1016/j.chom.2021.01.015 doi:10.1016/j.chom.2021.01.015 pmid:33548198 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) IFN activity Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-523) was tested in vitro for IFN response. Lin 2021 https://doi.org/10.1016/j.chom.2021.01.015 doi:10.1016/j.chom.2021.01.015 pmid:33548198 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,507,508,508,509,509,510,510,513,514,514,515,515,517,517,518,508,510,514,517,518,520 M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,M85del,V86del,V86del,V86del,V86del,V86del,V86del NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.252_254del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.253_255del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del,NC_045512.2(GU280_gp01):g.257_259del YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Met85del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del,YP_009724389.1:p.Val86del open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) IFN activity Deletions in the genomic nucleotide 500-523 range are shown in vitro culture to downregulated interferon A1/2 & B1 expression, and are associated with lower clinical severity of disease (Jan-Mar 2020 in China). variations of deletion in this region are found in separate lineages throughout the globe. This specific deletion (genomic 509-517) was tested in vitro for IFN response. Lin 2021 https://doi.org/10.1016/j.chom.2021.01.015 doi:10.1016/j.chom.2021.01.015 pmid:33548198 True Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 507,509,518 M85V,M85V,M85V NC_045512.2(GU280_gp01):g.253A>G,NC_045512.2(GU280_gp01):g.253A>G,NC_045512.2(GU280_gp01):g.253A>G YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val,YP_009724389.1:p.Met85Val open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 508 H81Q NC_045512.2(GU280_gp01):g.243T>A YP_009724389.1:p.His81Gln open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (30x overrepresentation vs expected count of ~20 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 510 M85K NC_045512.2(GU280_gp01):g.254T>A YP_009724389.1:p.Met85Lys open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~12 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 561 R99H NC_045512.2(GU280_gp01):g.296G>A YP_009724389.1:p.Arg99His open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (17x overrepresentation vs expected count of ~143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 563 S100C NC_045512.2(GU280_gp01):g.298A>T YP_009724389.1:p.Ser100Cys open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (33x overrepresentation vs expected count of ~19 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 592,593 H110Y,H110Y ,NC_045512.2(GU280_gp01):g.328C>T YP_009724389.1:p.His110Tyr,YP_009724389.1:p.His110Tyr open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (22x overrepresentation vs expected count of ~514 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 593 H110D NC_045512.2(GU280_gp01):g.328C>G YP_009724389.1:p.His110Asp open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (12x overrepresentation vs expected count of ~11 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 606 I114T NC_045512.2(GU280_gp01):g.341T>C YP_009724389.1:p.Ile114Thr open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (155x overrepresentation vs expected count of ~58 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 657 A131V NC_045512.2(GU280_gp01):g.392C>T YP_009724389.1:p.Ala131Val open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~514 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 677 A138T NC_045512.2(GU280_gp01):g.412G>A YP_009724389.1:p.Ala138Thr open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (14x overrepresentation vs expected count of ~143 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 761 S166G NC_045512.2(GU280_gp01):g.496A>G YP_009724389.1:p.Ser166Gly open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (132x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay +Severe acute respiratory syndrome coronavirus 2 NC_045512.2 RefSeq 798 N178S NC_045512.2(GU280_gp01):g.533A>G YP_009724389.1:p.Asn178Ser open reading frame 1ab gene (SARS-CoV-2) orf1ab gene (SARS-CoV-2) open reading frame 1a polyprotein (SARS-CoV-2) Orf1a protein (SARS-CoV-2) frequency based fitness Calculated to have an increased fitness (13x overrepresentation vs expected count of ~65 in public genome datasets) 2023 https://doi.org/10.1101/2023.01.30.526314 doi:10.1101/2023.01.30.526314 pmid:36778462 False Paul Gordon Pokay From 3739a4a0081d31451f5fc87fa24425c94b6c8754 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 9 Dec 2024 15:33:08 -0800 Subject: [PATCH 134/161] updated output files to match gvf naming --- modules/local/gvf2tsv.nf | 2 +- modules/local/tsv2pdf.nf | 6 +----- 2 files changed, 2 insertions(+), 6 deletions(-) diff --git a/modules/local/gvf2tsv.nf b/modules/local/gvf2tsv.nf index 4b6e26ab..b3f61acf 100644 --- a/modules/local/gvf2tsv.nf +++ b/modules/local/gvf2tsv.nf @@ -25,7 +25,7 @@ process GVF2TSV { gvf2tsv.py \\ --gvf_file ${gvf} \\ ${args} \\ - --outtsv ${prefix}.tsv + --outtsv ${prefix}_annotated.tsv cat <<-END_VERSIONS > versions.yml "${task.process}": diff --git a/modules/local/tsv2pdf.nf b/modules/local/tsv2pdf.nf index 91ed6f4f..3a54411d 100644 --- a/modules/local/tsv2pdf.nf +++ b/modules/local/tsv2pdf.nf @@ -19,15 +19,11 @@ process TSV2PDF { def prefix = task.ext.prefix ?: "${meta.id}" """ - echo "Inputs:" - echo "TSV file: ${tsv}" - echo "Indicators file: ${surveillanceindicators}" - echo "Metadata: ${metadata}" surveillance_report_pdf.py \ --tsv ${tsv} \ --functions_table ${surveillanceindicators} \ ${metadata_arg} \ ${virusseq_arg} \ - --output ${prefix}.pdf + --output ${prefix}_annotated.pdf """ } From baeb989c894cdf9f6fa84d890a39e11423502e58 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 9 Dec 2024 15:59:44 -0800 Subject: [PATCH 135/161] update sars-cov-2 test data --- data/sars-cov-2/sars-cov-2_test_data_100x.fa | 200 ++++++++++++++++++ data/sars-cov-2/sars-cov-2_test_data_10x.fa | 20 ++ data/sars-cov-2/sars-cov-2_test_data_1x.fa | 2 + data/sars-cov-2/sars-cov-2_test_data_25x.fa | 50 +++++ data/sars-cov-2/sars-cov-2_test_data_50x.fa | 100 +++++++++ data/sars-cov-2/sars-cov-2_test_data_5x.fa | 10 + .../sars-cov-2/sars-cov-2_test_data_100x.fa | 200 ++++++++++++++++++ .../sars-cov-2/sars-cov-2_test_data_10x.fa | 20 ++ .../sars-cov-2/sars-cov-2_test_data_1x.fa | 2 + .../sars-cov-2/sars-cov-2_test_data_25x.fa | 50 +++++ .../sars-cov-2/sars-cov-2_test_data_50x.fa | 100 +++++++++ .../sars-cov-2/sars-cov-2_test_data_5x.fa | 10 + 12 files changed, 764 insertions(+) create mode 100644 data/sars-cov-2/sars-cov-2_test_data_100x.fa create mode 100644 data/sars-cov-2/sars-cov-2_test_data_10x.fa create mode 100644 data/sars-cov-2/sars-cov-2_test_data_1x.fa create mode 100644 data/sars-cov-2/sars-cov-2_test_data_25x.fa create mode 100644 data/sars-cov-2/sars-cov-2_test_data_50x.fa create mode 100644 data/sars-cov-2/sars-cov-2_test_data_5x.fa create mode 100644 test_data/sars-cov-2/sars-cov-2_test_data_100x.fa create mode 100644 test_data/sars-cov-2/sars-cov-2_test_data_10x.fa create mode 100644 test_data/sars-cov-2/sars-cov-2_test_data_1x.fa create mode 100644 test_data/sars-cov-2/sars-cov-2_test_data_25x.fa create mode 100644 test_data/sars-cov-2/sars-cov-2_test_data_50x.fa create mode 100644 test_data/sars-cov-2/sars-cov-2_test_data_5x.fa diff --git a/data/sars-cov-2/sars-cov-2_test_data_100x.fa b/data/sars-cov-2/sars-cov-2_test_data_100x.fa new file mode 100644 index 00000000..b4d730fd --- /dev/null +++ b/data/sars-cov-2/sars-cov-2_test_data_100x.fa @@ -0,0 +1,200 @@ +>hCoV-19/Canada/ON-SLB3081/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3139/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3086/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00408926001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00245966/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0450/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTTGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCAAAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTGTACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAATCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAATATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACTGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGTCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGTCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTTTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCTCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAACAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8150877C2/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-SLB3103/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3141/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACATTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTAYCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3105/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGATTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3076/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3167/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTTAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGYTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTCCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTTTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGATAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIUM-U0182948/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAATCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACTAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCNNNNNNTTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACTTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACGTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATTTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTATTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAATCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTATTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAGATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGATTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGATATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTTTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATCCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTCTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATCTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGACTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00368847001A/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCTGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAGCAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTTCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATTAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCATTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGTGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCGTATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTTGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00596829001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATTAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAGACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTACGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTGTTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN 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+NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTCGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTTAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTTTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTATAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACCGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACATTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCACTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGTTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCGTTTGGAATCTTGATTATATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAATTCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTATAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGTTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00609962001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGTTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTTTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGAAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTTAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTAGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATTTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGGAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATTCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTATCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCCACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAGCATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCATATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAGAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCGAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACGAAAACAACAAAAGTCGGATGGAAAGTGAGTTAAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTTTTATGGACCTTGAAGGAAAACAGGGTGATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTGTTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAAGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTAGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTCTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCAGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGTTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTTTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCATTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3121/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACAYCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCNCCTAATATGATGGTAACAAACAATACCTTCAYACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTNNNNNNNNNNNNNNNNNNNNNNNNNNTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAARGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCTTGCATACACTMATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTANNNNNNNNGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTNNNNACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGAGCCTGAAGAACATGTCCAAATTCACACAATNNACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIID-V0183354/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGATCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTATTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTNTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAAGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTTGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTTGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGTCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGTGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCTCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTTGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTTAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00384111001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTATTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAATAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAATACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAATTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGGATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nSKP-0636208995/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGNCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAGGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNNNGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGNNGCTGTAGACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTGAAATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTTGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00567417001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAATTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAAATCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAANTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACTTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGTTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACTATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATTCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCTGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGGTTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGACTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTCAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8020395/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTCTTGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTTAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAATCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAATGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAAAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACTCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTTCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGTTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTGTTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAATAAAGGGCGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGATTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTTTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTTTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGCAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAACAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCGCTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGTGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGGCCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAACCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCTCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00414073001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAATAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGTATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAAGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGACGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACTACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTTTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAATTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACAGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGSGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACGAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGTTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAATTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGATACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGGCTTTAGCTTGTGGGTTTACAAACAATTTGATATTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATANNNNNNCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGTAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAAAAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGTAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACGCGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTATTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTACTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGTGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAGGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCATATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00345776001/2021 +AGATCTATTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGACGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTGCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACGTTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTTGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAATTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACTCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTACGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCGAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTTAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATKACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAATAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTTTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACCAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATTTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTRTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCGCTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGTCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTTTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATTAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATACAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00244596/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTATGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATTC +>hCoV-19/Canada/QC-JUS-V6011941/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0418/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00466204001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTTACCTGTGCAAAGGAAATTAATGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAATCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTNNCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0435/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATTTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTATATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN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TTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0480/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGNTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00501697001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTACTGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAATTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATATAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTCGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACTAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCTATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAAGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0437/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0463/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGTTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATTCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTNCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATAGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGGTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCTTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-JUS-V5290830/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTYGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTTATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0458/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACCGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0456/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0451/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTTTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00500193001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAAATCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATNNNNNNNNNNNNNNNNNNGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATAGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGTTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTACAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCATCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0415/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAATGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAATTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGATGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAACACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACGTGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTATACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAATAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTACATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCCTTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGTTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTTTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCTATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCATTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTATTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACTAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCTAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0484/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTGTTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAGACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTTGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTCTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAATACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGTAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTATGAAGTATTTTGTGAAAATAGGACCTGAGTGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCTTTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCTAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTATTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0462/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTATCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIEOQ-S8098799/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAATGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAATAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0481/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0423/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/Qc-HSJ-T8074357/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAATAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0464/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCCACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00369301001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATTCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGACTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATTTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATTGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATTTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAATTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCACACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGTTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAANCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAACCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTTCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTTAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTTCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGTTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00537936001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCGCATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTAAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGTTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAATAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAATTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGGCTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00338868001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCATCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCGGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGCGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGTTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAATAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTACTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAA +>hCoV-19/Canada/QC-L00555756001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAACAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAGTTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAATATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATYTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACACTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-CHUM-2007801609A/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTACCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTNNNNNNNNNNNNNGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00532342001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGATACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTANNTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATTTTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-CHUS-473818731/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTTCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATAGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGTCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTTTAACATAATAGGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTTTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTTGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTTATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTTAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-LSPQ-L00584454001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGTTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAATATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTATAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACATAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTWTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGTGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGCTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATNNNNNTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCTAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTTAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0488/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00656639001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTTAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATGGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGATATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCAGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTGGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCGGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCATACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGTAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGTTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAGACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCAACAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCATCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGAAACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTACTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGCTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAACCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAGCATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGATAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCCCATGTGATTTTAATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00538903001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGTAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTTAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATTTTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00528329001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACAGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGTATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGTATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAATAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTGAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAATTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXP-8143490664/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCKTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAATATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGATACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTTCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATTCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCTCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCTAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGMAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAATGAAAATGGANNNATTACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACATACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAGGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATTAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nDJLG-R4162282/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGTTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACTCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTTCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATTTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATAGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAATCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCTCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGGTATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTTAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACACAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00612192001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGTGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGTTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAATATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATTTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATTGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACATAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTATAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGTGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTGGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGCTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACATTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCTAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTTAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXW-511485281/2022 +TTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAGGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCGGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATATAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTACTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTCAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGTTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTGTTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTCACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAATATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGTTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCATTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTATAGTGCGTGAGCCAGAAGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATCTCGCACCATTTTTCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATAGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAAAAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTANNTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAAAGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCTTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTTTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGGTTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCCAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGGTCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTA +>hCoV-19/Canada/QC-1nDJXP-8143732050/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATATACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGAAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAATATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGATACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATTCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCTCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCTAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTGTCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATNNNNTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTANTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGTTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACATACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAGGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATTAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00622377001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATCGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATTATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTGGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTTTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGAAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTTAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATTTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATTCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACCATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACATCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAGCATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCATATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCGAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACGAAAACAACAAAAGTCGGATGGAAAGTGAGTTAAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTGTTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAAGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTAGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTCTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAACCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACCCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCCCATGTGATTTTAATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00484774001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACCTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAGCTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTTTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATTAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0471/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCTTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00504249001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNCGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCNNNNTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAACGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATGAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTATTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGCAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTGAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCAGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTTAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACTCAGGTTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCTCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-2032905072A/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGATTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGGTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00499441001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTGTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGTAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCTAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00338802001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGCTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAAGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTTATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTTAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAA +>hCoV-19/Canada/QC-L00370688001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCATATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGTCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAACCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACTTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAATTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGATTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTTTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTTTGACCAGACCGCTTCTAGAAAGTGAACTAGTAATCGGAGCTGTCATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGTTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGATGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00492179001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTATCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTATAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00508517001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTTGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGACCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGTATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTWTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGTATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAATAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCTTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIEOQ-U40633579Q/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAATATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGATACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATTCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCTCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCTAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACATACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAGGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATTAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nMCY-T0161612/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTCGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCTTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAATCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTCTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACTAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGGAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTGGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGTCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTATGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACAACACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCATTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACCTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTATTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACACGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGACGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGACACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTNNNNNNNNATTACCACAAAAACAACAAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAGCCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAAGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTTCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGTAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTTCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTTCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTCACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTATAATGTCTGATAATGGACTCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGATGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTTAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCATCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACTGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00559276001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAACCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAGTTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTTGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAACTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8251693C2/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTATTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCTAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCATGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACGGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGTTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCACACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCCTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nKWV-W9062318/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATNNNNNNCCTNNNNNTNNNNNNNNNNNNNNNGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGNTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTYTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTTTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTTATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00367589001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTTTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCATACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGTTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGATATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATTTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCCCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAANTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTTGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCTTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCATGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTCTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTTTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATATTAATTGTTATGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACACGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTTAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACCCAGGCCTAAACTCATGCATACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00609385001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGATGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGGGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTAAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGGTGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCTTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGCTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTGCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAATGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGGTATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00521508001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTTCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTGTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTTTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTTGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGTAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCTAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIOU-A4182885/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACGCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCTTTGCACCCAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACATGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCTACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAATAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACTTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGATTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGACGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGTAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGTCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTTATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTTCTAGAATCGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00537408001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGCTGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTNGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAGTTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACTTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCATACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTATTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCTTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATTTTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDWVQ-MX21186518/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATTGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTATAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCATATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGATACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-LSPQ-L00584154001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCTTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAATTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAAACACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACTAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAATTTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCRCACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN 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+NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGGGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTATTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAGTTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGATTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAATTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN 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+NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGATAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTAGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATTTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTATAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGCGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGGTTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCATCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCGAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGTTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTGTTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGTACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00567252001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTTGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGCGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCATCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAACGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCTTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGNNNCTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACNNNGCTTAAAAAGTGTAAAAGTGCNTTTTACNNNNNNNNNNNNATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATTCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTGGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTCGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAATCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTTACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACCGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00394372001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGTACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCATCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTGTTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCGAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGAATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTGCAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAATCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCTTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTCGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACACCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATTATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00488234001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGTTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTATTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGGGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTATTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTWTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTATATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCAGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTTAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAGTTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTTATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00504857001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAGGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGACTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTATAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTTTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCATGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIOU-A4293969/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACGCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCCAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACATGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGNNNNNNNNAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTTGGTTTTTACTATTAAGTGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCTACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAATAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACTTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGATTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATTACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGACGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGTAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGTCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTTATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATCGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGC +>hCoV-19/Canada/QC-L00610702001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAATATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTCTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTGTGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCTATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTGGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTCTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTTATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCATACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00378724001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATTGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGATTACTACCACACAACTGATCTTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACGCTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTTTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGTTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGCTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAATTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAATAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTTTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGTTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTATAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCTTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGTTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nDJXW-505000201/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTATAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAATGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTATACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACNNTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAAGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAGCTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAATCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAATAAGCTTTGTGAAGAAATGCTGTACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTGTACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACTTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATTACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTGACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATTAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACTCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTTGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00482194001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTATTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGACCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTWTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGATTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGATTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCAGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTTAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACATCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00450298001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATATTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCTGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAACTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00576722001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGCACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATTTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAATCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTCAGACGCTGATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00501172001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAAGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTAATGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATATACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN diff --git a/data/sars-cov-2/sars-cov-2_test_data_10x.fa b/data/sars-cov-2/sars-cov-2_test_data_10x.fa new file mode 100644 index 00000000..84f3148e --- /dev/null +++ b/data/sars-cov-2/sars-cov-2_test_data_10x.fa @@ -0,0 +1,20 @@ +>hCoV-19/Canada/ON-SLB3081/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3139/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3086/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00408926001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00245966/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0450/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTTGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCAAAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTGTACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAATCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAATATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACTGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGTCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGTCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTTTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCTCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAACAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8150877C2/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-SLB3103/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3141/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACATTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTAYCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3105/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGATTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN diff --git a/data/sars-cov-2/sars-cov-2_test_data_1x.fa b/data/sars-cov-2/sars-cov-2_test_data_1x.fa new file mode 100644 index 00000000..c641227d --- /dev/null +++ b/data/sars-cov-2/sars-cov-2_test_data_1x.fa @@ -0,0 +1,2 @@ +>hCoV-19/Canada/ON-SLB3081/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN diff --git a/data/sars-cov-2/sars-cov-2_test_data_25x.fa b/data/sars-cov-2/sars-cov-2_test_data_25x.fa new file mode 100644 index 00000000..ec826315 --- /dev/null +++ b/data/sars-cov-2/sars-cov-2_test_data_25x.fa @@ -0,0 +1,50 @@ +>hCoV-19/Canada/ON-SLB3081/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3139/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3086/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00408926001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00245966/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0450/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTTGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCAAAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTGTACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAATCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAATATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACTGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGTCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGTCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTTTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCTCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAACAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8150877C2/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-SLB3103/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3141/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACATTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTAYCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3105/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGATTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3076/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3167/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTTAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGYTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTCCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTTTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGATAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIUM-U0182948/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAATCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACTAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCNNNNNNTTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACTTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACGTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATTTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTATTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAATCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTATTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAGATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGATTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGATATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTTTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATCCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTCTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATCTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGACTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00368847001A/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCTGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAGCAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTTCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATTAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCATTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGTGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCGTATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTTGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00596829001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATTAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAGACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTACGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTGTTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN 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+NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTCGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTTAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTTTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTATAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACCGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACATTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCACTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGTTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCGTTTGGAATCTTGATTATATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAATTCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTATAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGTTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00609962001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGTTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTTTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGAAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTTAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTAGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATTTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGGAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATTCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTATCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCCACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAGCATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCATATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAGAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCGAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACGAAAACAACAAAAGTCGGATGGAAAGTGAGTTAAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTTTTATGGACCTTGAAGGAAAACAGGGTGATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTGTTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAAGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTAGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTCTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCAGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGTTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTTTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCATTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3121/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACAYCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCNCCTAATATGATGGTAACAAACAATACCTTCAYACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTNNNNNNNNNNNNNNNNNNNNNNNNNNTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAARGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCTTGCATACACTMATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTANNNNNNNNGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTNNNNACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGAGCCTGAAGAACATGTCCAAATTCACACAATNNACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIID-V0183354/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGATCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTATTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTNTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAAGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTTGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTTGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGTCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGTGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCTCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTTGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTTAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00384111001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTATTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAATAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAATACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAATTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGGATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nSKP-0636208995/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGNCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAGGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNNNGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGNNGCTGTAGACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTGAAATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTTGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00567417001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAATTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAAATCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAANTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACTTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGTTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACTATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATTCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCTGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGGTTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGACTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTCAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8020395/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTCTTGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTTAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAATCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAATGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAAAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACTCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTTCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGTTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTGTTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAATAAAGGGCGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGATTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTTTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTTTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGCAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAACAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCGCTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGTGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGGCCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAACCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCTCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00414073001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAATAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGTATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAAGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGACGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACTACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTTTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAATTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACAGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGSGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACGAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGTTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAATTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGATACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGGCTTTAGCTTGTGGGTTTACAAACAATTTGATATTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATANNNNNNCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGTAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAAAAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGTAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACGCGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTATTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTACTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGTGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAGGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCATATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00345776001/2021 +AGATCTATTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGACGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTGCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACGTTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTTGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAATTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACTCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTACGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCGAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTTAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATKACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAATAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTTTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACCAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATTTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTRTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCGCTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGTCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTTTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATTAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATACAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC diff --git a/data/sars-cov-2/sars-cov-2_test_data_50x.fa b/data/sars-cov-2/sars-cov-2_test_data_50x.fa new file mode 100644 index 00000000..aee72a4d --- /dev/null +++ b/data/sars-cov-2/sars-cov-2_test_data_50x.fa @@ -0,0 +1,100 @@ +>hCoV-19/Canada/ON-SLB3081/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3139/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3086/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00408926001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00245966/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0450/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTTGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCAAAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTGTACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAATCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAATATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACTGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGTCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGTCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTTTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCTCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAACAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8150877C2/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-SLB3103/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3141/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACATTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTAYCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3105/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGATTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3076/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3167/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTTAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGYTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTCCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTTTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGATAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIUM-U0182948/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAATCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACTAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCNNNNNNTTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACTTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACGTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATTTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTATTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAATCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTATTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAGATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGATTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGATATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTTTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATCCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTCTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATCTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGACTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00368847001A/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCTGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAGCAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTTCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATTAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCATTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGTGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCGTATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTTGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00596829001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATTAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAGACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTACGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTGTTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN 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+NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTCGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTTAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTTTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTATAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACCGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACATTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCACTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGTTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCGTTTGGAATCTTGATTATATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAATTCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTATAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGTTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00609962001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGTTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTTTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGAAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTTAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTAGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATTTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGGAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATTCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTATCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCCACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAGCATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCATATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAGAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCGAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACGAAAACAACAAAAGTCGGATGGAAAGTGAGTTAAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTTTTATGGACCTTGAAGGAAAACAGGGTGATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTGTTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAAGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTAGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTCTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCAGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGTTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTTTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCATTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3121/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACAYCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCNCCTAATATGATGGTAACAAACAATACCTTCAYACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTNNNNNNNNNNNNNNNNNNNNNNNNNNTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAARGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCTTGCATACACTMATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTANNNNNNNNGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTNNNNACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGAGCCTGAAGAACATGTCCAAATTCACACAATNNACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIID-V0183354/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGATCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTATTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTNTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAAGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTTGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTTGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGTCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGTGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCTCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTTGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTTAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00384111001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTATTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAATAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAATACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAATTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGGATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nSKP-0636208995/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGNCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAGGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNNNGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGNNGCTGTAGACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTGAAATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTTGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00567417001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAATTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAAATCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAANTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACTTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGTTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACTATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATTCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCTGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGGTTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGACTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTCAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8020395/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTCTTGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTTAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAATCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAATGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAAAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACTCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTTCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGTTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTGTTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAATAAAGGGCGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGATTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTTTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTTTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGCAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAACAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCGCTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGTGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGGCCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAACCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCTCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00414073001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAATAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGTATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAAGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGACGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACTACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTTTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAATTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACAGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGSGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACGAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGTTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAATTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGATACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGGCTTTAGCTTGTGGGTTTACAAACAATTTGATATTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATANNNNNNCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGTAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAAAAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGTAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACGCGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTATTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTACTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGTGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAGGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCATATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00345776001/2021 +AGATCTATTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGACGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTGCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACGTTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTTGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAATTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACTCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTACGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCGAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTTAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATKACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAATAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTTTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACCAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATTTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTRTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCGCTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGTCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTTTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATTAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATACAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00244596/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTATGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATTC +>hCoV-19/Canada/QC-JUS-V6011941/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0418/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00466204001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTTACCTGTGCAAAGGAAATTAATGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAATCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTNNCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0435/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATTTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTATATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN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TTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0480/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGNTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00501697001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTACTGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAATTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATATAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTCGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACTAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCTATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAAGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0437/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0463/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGTTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATTCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTNCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATAGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGGTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCTTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-JUS-V5290830/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTYGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTTATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0458/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACCGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0456/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0451/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTTTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00500193001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAAATCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATNNNNNNNNNNNNNNNNNNGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATAGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGTTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTACAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCATCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0415/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAATGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAATTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGATGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAACACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACGTGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTATACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAATAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTACATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCCTTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGTTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTTTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCTATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCATTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTATTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACTAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCTAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0484/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTGTTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAGACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTTGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTCTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAATACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGTAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTATGAAGTATTTTGTGAAAATAGGACCTGAGTGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCTTTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCTAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTATTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0462/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTATCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIEOQ-S8098799/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAATGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAATAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0481/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0423/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/Qc-HSJ-T8074357/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAATAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0464/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCCACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00369301001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATTCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGACTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATTTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATTGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATTTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAATTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCACACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGTTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAANCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAACCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTTCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTTAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTTCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGTTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00537936001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCGCATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTAAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGTTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAATAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAATTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGGCTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00338868001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCATCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCGGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGCGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGTTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAATAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTACTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAA diff --git a/data/sars-cov-2/sars-cov-2_test_data_5x.fa b/data/sars-cov-2/sars-cov-2_test_data_5x.fa new file mode 100644 index 00000000..d59fc34c --- /dev/null +++ b/data/sars-cov-2/sars-cov-2_test_data_5x.fa @@ -0,0 +1,10 @@ +>hCoV-19/Canada/ON-SLB3081/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3139/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3086/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00408926001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00245966/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC diff --git a/test_data/sars-cov-2/sars-cov-2_test_data_100x.fa b/test_data/sars-cov-2/sars-cov-2_test_data_100x.fa new file mode 100644 index 00000000..b4d730fd --- /dev/null +++ b/test_data/sars-cov-2/sars-cov-2_test_data_100x.fa @@ -0,0 +1,200 @@ +>hCoV-19/Canada/ON-SLB3081/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3139/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3086/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00408926001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00245966/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0450/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTTGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCAAAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTGTACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAATCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAATATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACTGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGTCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGTCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTTTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCTCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAACAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8150877C2/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-SLB3103/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3141/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACATTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTAYCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3105/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGATTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3076/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3167/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTTAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGYTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTCCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTTTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGATAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIUM-U0182948/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAATCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACTAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCNNNNNNTTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACTTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACGTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATTTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTATTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAATCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTATTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAGATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGATTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGATATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTTTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATCCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTCTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATCTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGACTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00368847001A/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCTGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAGCAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTTCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATTAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCATTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGTGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCGTATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTTGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00596829001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATTAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAGACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTACGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTGTTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN 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+NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTCGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTTAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTTTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTATAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACCGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACATTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCACTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGTTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCGTTTGGAATCTTGATTATATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAATTCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTATAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGTTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00609962001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGTTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTTTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGAAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTTAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTAGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATTTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGGAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATTCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTATCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCCACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAGCATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCATATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAGAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCGAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACGAAAACAACAAAAGTCGGATGGAAAGTGAGTTAAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTTTTATGGACCTTGAAGGAAAACAGGGTGATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTGTTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAAGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTAGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTCTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCAGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGTTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTTTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCATTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3121/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACAYCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCNCCTAATATGATGGTAACAAACAATACCTTCAYACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTNNNNNNNNNNNNNNNNNNNNNNNNNNTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAARGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCTTGCATACACTMATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTANNNNNNNNGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTNNNNACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGAGCCTGAAGAACATGTCCAAATTCACACAATNNACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIID-V0183354/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGATCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTATTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTNTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAAGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTTGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTTGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGTCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGTGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCTCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTTGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTTAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00384111001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTATTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAATAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAATACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAATTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGGATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nSKP-0636208995/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGNCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAGGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNNNGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGNNGCTGTAGACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTGAAATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTTGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00567417001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAATTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAAATCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAANTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACTTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGTTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACTATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATTCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCTGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGGTTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGACTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTCAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8020395/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTCTTGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTTAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAATCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAATGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAAAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACTCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTTCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGTTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTGTTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAATAAAGGGCGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGATTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTTTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTTTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGCAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAACAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCGCTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGTGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGGCCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAACCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCTCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00414073001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAATAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGTATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAAGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGACGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACTACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTTTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAATTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACAGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGSGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACGAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGTTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAATTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGATACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGGCTTTAGCTTGTGGGTTTACAAACAATTTGATATTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATANNNNNNCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGTAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAAAAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGTAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACGCGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTATTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTACTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGTGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAGGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCATATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00345776001/2021 +AGATCTATTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGACGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTGCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACGTTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTTGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAATTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACTCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTACGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCGAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTTAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATKACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAATAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTTTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACCAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATTTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTRTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCGCTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGTCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTTTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATTAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATACAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00244596/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTATGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATTC +>hCoV-19/Canada/QC-JUS-V6011941/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0418/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00466204001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTTACCTGTGCAAAGGAAATTAATGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAATCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTNNCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0435/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATTTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTATATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN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TTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0480/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGNTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00501697001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTACTGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAATTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATATAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTCGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACTAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCTATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAAGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0437/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0463/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGTTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATTCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTNCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATAGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGGTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCTTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-JUS-V5290830/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTYGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTTATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0458/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACCGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0456/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0451/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTTTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00500193001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAAATCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATNNNNNNNNNNNNNNNNNNGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATAGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGTTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTACAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCATCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0415/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAATGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAATTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGATGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAACACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACGTGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTATACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAATAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTACATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCCTTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGTTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTTTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCTATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCATTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTATTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACTAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCTAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0484/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTGTTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAGACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTTGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTCTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAATACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGTAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTATGAAGTATTTTGTGAAAATAGGACCTGAGTGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCTTTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCTAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTATTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0462/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTATCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIEOQ-S8098799/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAATGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAATAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0481/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0423/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/Qc-HSJ-T8074357/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAATAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0464/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCCACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00369301001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATTCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGACTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATTTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATTGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATTTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAATTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCACACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGTTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAANCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAACCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTTCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTTAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTTCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGTTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00537936001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCGCATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTAAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGTTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAATAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAATTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGGCTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00338868001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCATCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCGGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGCGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGTTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAATAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTACTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAA +>hCoV-19/Canada/QC-L00555756001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAACAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAGTTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAATATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATYTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACACTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-CHUM-2007801609A/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTACCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTNNNNNNNNNNNNNGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00532342001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGATACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTANNTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATTTTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-CHUS-473818731/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTTCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATAGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGTCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTTTAACATAATAGGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTTTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTTGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTTATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTTAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-LSPQ-L00584454001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGTTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAATATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTATAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACATAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTWTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGTGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGCTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATNNNNNTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCTAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTTAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0488/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00656639001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTTAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATGGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGATATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCAGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTGGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCGGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCATACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGTAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGTTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAGACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCAACAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCATCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGAAACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTACTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGCTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAACCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAGCATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGATAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCCCATGTGATTTTAATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00538903001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGTAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTTAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATTTTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00528329001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACAGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGTATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGTATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAATAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTGAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAATTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXP-8143490664/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCKTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAATATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGATACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTTCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATTCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCTCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCTAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGMAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAATGAAAATGGANNNATTACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACATACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAGGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATTAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nDJLG-R4162282/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGTTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACTCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTTCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATTTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATAGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAATCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCTCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGGTATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTTAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACACAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00612192001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGTGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGTTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAATATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATTTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATTGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACATAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTATAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGTGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTGGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGCTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACATTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCTAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTTAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXW-511485281/2022 +TTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAGGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCGGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATATAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTACTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTCAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGTTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTGTTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTCACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAATATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGTTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCATTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTATAGTGCGTGAGCCAGAAGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATCTCGCACCATTTTTCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATAGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAAAAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTANNTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAAAGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCTTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTTTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGGTTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCCAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGGTCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTA +>hCoV-19/Canada/QC-1nDJXP-8143732050/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATATACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGAAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAATATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGATACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATTCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCTCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCTAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTGTCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATNNNNTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTANTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGTTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACATACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAGGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATTAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00622377001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATCGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATTATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTGGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTTTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGAAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTTAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATTTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATTCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACCATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACATCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAGCATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCATATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCGAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACGAAAACAACAAAAGTCGGATGGAAAGTGAGTTAAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTGTTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAAGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTAGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTCTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAACCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACCCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCCCATGTGATTTTAATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00484774001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACCTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAGCTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTTTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATTAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0471/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCTTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00504249001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNCGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCNNNNTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAACGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATGAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTATTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGCAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTGAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCAGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTTAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACTCAGGTTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCTCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-2032905072A/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGATTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGGTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00499441001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTGTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGTAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCTAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00338802001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGCTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAAGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTTATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTTAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAA +>hCoV-19/Canada/QC-L00370688001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCATATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGTCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAACCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACTTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAATTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGATTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTTTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTTTGACCAGACCGCTTCTAGAAAGTGAACTAGTAATCGGAGCTGTCATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGTTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGATGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00492179001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTATCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTATAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00508517001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTTGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGACCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGTATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTWTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGTATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAATAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCTTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIEOQ-U40633579Q/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAATATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGATACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATTCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCTCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCTAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACATACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAGGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATTAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nMCY-T0161612/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTCGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCTTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAATCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTCTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACTAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGGAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTGGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGTCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTATGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACAACACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCATTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACCTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTATTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACACGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGACGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGACACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTNNNNNNNNATTACCACAAAAACAACAAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAGCCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAAGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTTCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGTAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTTCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTTCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTCACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTATAATGTCTGATAATGGACTCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGATGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTTAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCATCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACTGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00559276001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAACCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAGTTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTTGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAACTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8251693C2/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTATTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCTAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCATGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACGGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGTTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCACACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCCTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nKWV-W9062318/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATNNNNNNCCTNNNNNTNNNNNNNNNNNNNNNGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGNTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTYTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTTTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTTATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00367589001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTTTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCATACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGTTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGATATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATTTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCCCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAANTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTTGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCTTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCATGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTCTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTTTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATATTAATTGTTATGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACACGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTTAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACCCAGGCCTAAACTCATGCATACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00609385001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGATGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGGGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTAAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGGTGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCTTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGCTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTGCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAATGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGGTATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00521508001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTTCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTGTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTTTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTTGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGTAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCTAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIOU-A4182885/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACGCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCTTTGCACCCAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACATGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCTACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAATAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACTTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGATTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGACGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGTAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGTCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTTATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTTCTAGAATCGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00537408001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGCTGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTNGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAGTTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACTTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCATACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTATTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCTTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATTTTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDWVQ-MX21186518/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATTGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTATAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCATATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGATACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-LSPQ-L00584154001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCTTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAATTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAAACACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACTAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAATTTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCRCACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN 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+NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGGGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTATTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAGTTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGATTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAATTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN 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+NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGATAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTAGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATTTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTATAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGCGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGGTTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCATCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCGAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGTTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTGTTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGTACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00567252001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTTGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGCGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCATCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAACGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCTTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGNNNCTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACNNNGCTTAAAAAGTGTAAAAGTGCNTTTTACNNNNNNNNNNNNATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATTCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTGGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTCGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAATCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTTACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACCGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00394372001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGTACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCATCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTGTTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCGAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGAATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTGCAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAATCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCTTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTCGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACACCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATTATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00488234001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGTTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTATTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGGGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTATTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTWTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTATATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCAGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTTAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAGTTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTTATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00504857001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAGGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGACTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTATAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTTTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCATGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIOU-A4293969/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACGCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCCAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACATGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGNNNNNNNNAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTTGGTTTTTACTATTAAGTGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCTACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAATAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACTTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGATTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATTACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGACGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGTAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGTCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTTATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATCGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGC +>hCoV-19/Canada/QC-L00610702001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAATATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTCTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTGTGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCTATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTGGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTCTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTTATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCATACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00378724001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATTGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGATTACTACCACACAACTGATCTTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACGCTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTTTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGTTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGCTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAATTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAATAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTTTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGTTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTATAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCTTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGTTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nDJXW-505000201/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTATAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAATGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTATACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACNNTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAAGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAGCTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAATCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAATAAGCTTTGTGAAGAAATGCTGTACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTGTACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACTTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATTACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTGACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATTAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACTCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTTGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00482194001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTATTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGACCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTWTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGATTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGATTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCAGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTTAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACATCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00450298001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATATTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCTGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAACTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00576722001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGCACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATTTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAATCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTCAGACGCTGATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00501172001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAAGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTAATGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATATACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN diff --git a/test_data/sars-cov-2/sars-cov-2_test_data_10x.fa b/test_data/sars-cov-2/sars-cov-2_test_data_10x.fa new file mode 100644 index 00000000..84f3148e --- /dev/null +++ b/test_data/sars-cov-2/sars-cov-2_test_data_10x.fa @@ -0,0 +1,20 @@ +>hCoV-19/Canada/ON-SLB3081/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3139/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3086/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00408926001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00245966/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0450/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTTGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCAAAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTGTACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAATCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAATATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACTGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGTCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGTCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTTTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCTCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAACAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8150877C2/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-SLB3103/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3141/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACATTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTAYCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3105/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGATTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN diff --git a/test_data/sars-cov-2/sars-cov-2_test_data_1x.fa b/test_data/sars-cov-2/sars-cov-2_test_data_1x.fa new file mode 100644 index 00000000..c641227d --- /dev/null +++ b/test_data/sars-cov-2/sars-cov-2_test_data_1x.fa @@ -0,0 +1,2 @@ +>hCoV-19/Canada/ON-SLB3081/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN diff --git a/test_data/sars-cov-2/sars-cov-2_test_data_25x.fa b/test_data/sars-cov-2/sars-cov-2_test_data_25x.fa new file mode 100644 index 00000000..ec826315 --- /dev/null +++ b/test_data/sars-cov-2/sars-cov-2_test_data_25x.fa @@ -0,0 +1,50 @@ +>hCoV-19/Canada/ON-SLB3081/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3139/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3086/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00408926001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00245966/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0450/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTTGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCAAAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTGTACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAATCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAATATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACTGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGTCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGTCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTTTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCTCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAACAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8150877C2/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-SLB3103/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3141/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACATTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTAYCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3105/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGATTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3076/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3167/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTTAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGYTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTCCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTTTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGATAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIUM-U0182948/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAATCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACTAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCNNNNNNTTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACTTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACGTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATTTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTATTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAATCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTATTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAGATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGATTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGATATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTTTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATCCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTCTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATCTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGACTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00368847001A/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCTGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAGCAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTTCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATTAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCATTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGTGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCGTATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTTGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00596829001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATTAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAGACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTACGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTGTTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN 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+NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTCGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTTAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTTTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTATAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACCGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACATTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCACTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGTTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCGTTTGGAATCTTGATTATATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAATTCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTATAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGTTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00609962001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGTTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTTTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGAAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTTAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTAGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATTTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGGAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATTCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTATCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCCACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAGCATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCATATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAGAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCGAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACGAAAACAACAAAAGTCGGATGGAAAGTGAGTTAAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTTTTATGGACCTTGAAGGAAAACAGGGTGATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTGTTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAAGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTAGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTCTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCAGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGTTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTTTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCATTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3121/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACAYCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCNCCTAATATGATGGTAACAAACAATACCTTCAYACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTNNNNNNNNNNNNNNNNNNNNNNNNNNTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAARGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCTTGCATACACTMATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTANNNNNNNNGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTNNNNACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGAGCCTGAAGAACATGTCCAAATTCACACAATNNACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIID-V0183354/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGATCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTATTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTNTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAAGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTTGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTTGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGTCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGTGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCTCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTTGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTTAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00384111001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTATTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAATAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAATACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAATTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGGATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nSKP-0636208995/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGNCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAGGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNNNGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGNNGCTGTAGACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTGAAATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTTGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00567417001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAATTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAAATCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAANTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACTTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGTTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACTATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATTCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCTGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGGTTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGACTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTCAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8020395/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTCTTGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTTAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAATCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAATGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAAAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACTCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTTCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGTTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTGTTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAATAAAGGGCGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGATTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTTTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTTTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGCAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAACAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCGCTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGTGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGGCCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAACCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCTCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00414073001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAATAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGTATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAAGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGACGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACTACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTTTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAATTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACAGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGSGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACGAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGTTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAATTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGATACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGGCTTTAGCTTGTGGGTTTACAAACAATTTGATATTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATANNNNNNCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGTAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAAAAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGTAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACGCGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTATTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTACTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGTGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAGGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCATATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00345776001/2021 +AGATCTATTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGACGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTGCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACGTTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTTGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAATTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACTCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTACGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCGAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTTAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATKACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAATAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTTTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACCAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATTTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTRTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCGCTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGTCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTTTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATTAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATACAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC diff --git a/test_data/sars-cov-2/sars-cov-2_test_data_50x.fa b/test_data/sars-cov-2/sars-cov-2_test_data_50x.fa new file mode 100644 index 00000000..aee72a4d --- /dev/null +++ b/test_data/sars-cov-2/sars-cov-2_test_data_50x.fa @@ -0,0 +1,100 @@ +>hCoV-19/Canada/ON-SLB3081/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3139/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3086/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00408926001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00245966/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0450/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTTGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCAAAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTGTACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAATCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAATATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACTGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGTCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGTCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTTTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCTCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAACAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8150877C2/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-SLB3103/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3141/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACATTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTAYCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3105/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGATTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3076/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3167/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTTAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGYTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTCCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTTTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGATAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIUM-U0182948/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAATCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACTAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCNNNNNNTTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACTTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACGTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATTTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTATTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAATCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTATTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAGATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGATTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGATATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTTTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATCCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTCTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATCTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGACTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00368847001A/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCTGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAGCAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTTCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATTAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCATTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGTGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCGTATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTTGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00596829001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATTAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAGACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTACGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTGTTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN 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+NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTCGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTTAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTTTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTATAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACCGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACATTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCACTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGTTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCGTTTGGAATCTTGATTATATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAATTCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTATAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGTTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00609962001/2023 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGTTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTTTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGAAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTTAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTAGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATTTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGGAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATTCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTATCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCCACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAGCATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCATATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAGAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCGAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACGAAAACAACAAAAGTCGGATGGAAAGTGAGTTAAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTTTTATGGACCTTGAAGGAAAACAGGGTGATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTGTTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAAGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTAGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTCTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCAGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGTTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTTTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCATTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3121/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACAYCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCNCCTAATATGATGGTAACAAACAATACCTTCAYACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTNNNNNNNNNNNNNNNNNNNNNNNNNNTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAARGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCTTGCATACACTMATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTANNNNNNNNGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTNNNNACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGAGCCTGAAGAACATGTCCAAATTCACACAATNNACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIID-V0183354/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGATCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTATTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTNTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAAGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTTGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTTGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGTCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGTGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCTCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTTGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTTAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00384111001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTATTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAATAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAATACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAATTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGGATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-1nSKP-0636208995/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGNCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAGGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNNNGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGNNGCTGTAGACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTGAAATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTTGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00567417001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAATTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAAATCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAANTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACTTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGTTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACTATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATTCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCTGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGGTTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGACTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTCAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nDJXQ-Q8020395/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTCTTGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTTAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAATCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAATGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAAAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACTCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTTCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGTTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTGTTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAATAAAGGGCGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGATTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTTTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTTTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGCAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAACAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCGCTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGTGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGGCCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAACCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCTCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00414073001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAATAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGTATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAAGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGACGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACTACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTTTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAATTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACAGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGSGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACGAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGTTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAATTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGATACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGGCTTTAGCTTGTGGGTTTACAAACAATTTGATATTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATANNNNNNCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGTAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAAAAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGTAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACGCGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTATTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTACTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGTGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAGGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCATATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00345776001/2021 +AGATCTATTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGACGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTGCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACGTTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTTGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAATTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACTCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTACGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCGAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTTAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATKACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAATAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTTTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACCAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATTTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTRTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCGCTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGTCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTTTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATTAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATACAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00244596/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTATGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATTC +>hCoV-19/Canada/QC-JUS-V6011941/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0418/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00466204001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTTACCTGTGCAAAGGAAATTAATGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAATCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTNNCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0435/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATTTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTATATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN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TTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0480/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGNTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00501697001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTACTGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAATTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATATAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTCGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACTAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCTATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAAGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0437/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0463/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGTTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATTCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTNCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATAGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGGTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCTTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-JUS-V5290830/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTYGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTTATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0458/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACCGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0456/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0451/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTTTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00500193001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAAATCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATNNNNNNNNNNNNNNNNNNGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATAGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGTTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTACAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCATCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0415/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAATGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAATTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGATGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAACACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACGTGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTATACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAATAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTACATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCCTTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGTTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTTTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCTATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCATTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTATTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACTAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCTAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0484/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTGTTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAGACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTTGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTCTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAATACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGTAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTATGAAGTATTTTGTGAAAATAGGACCTGAGTGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCTTTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCTAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTATTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0462/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTATCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-1nIEOQ-S8098799/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAATGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAATAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0481/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-UHTC_0423/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/Qc-HSJ-T8074357/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAATAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/ON-UHTC_0464/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCCACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00369301001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATTCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGACTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATTTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATTGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATTTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAATTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCACACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGTTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAANCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAACCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTTCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTTAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTTCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGTTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC +>hCoV-19/Canada/QC-L00537936001/2022 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCGCATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTAAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGTTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAATAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAATTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGGCTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00338868001/2021 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCATCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCGGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGCGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGTTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAATAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTACTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAA diff --git a/test_data/sars-cov-2/sars-cov-2_test_data_5x.fa b/test_data/sars-cov-2/sars-cov-2_test_data_5x.fa new file mode 100644 index 00000000..d59fc34c --- /dev/null +++ b/test_data/sars-cov-2/sars-cov-2_test_data_5x.fa @@ -0,0 +1,10 @@ +>hCoV-19/Canada/ON-SLB3081/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3139/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/ON-SLB3086/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00408926001/2021 +NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN +>hCoV-19/Canada/QC-L00245966/2020 +AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC From c6b41b75b7fe1300f4eb5b3c4b5e8c7cfb989d62 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 9 Dec 2024 16:00:14 -0800 Subject: [PATCH 136/161] update sars-cov-2 test data --- data/sars-cov-2/sars-cov-2_test_data_100x.fa | 200 ------------------- data/sars-cov-2/sars-cov-2_test_data_10x.fa | 20 -- data/sars-cov-2/sars-cov-2_test_data_1x.fa | 2 - data/sars-cov-2/sars-cov-2_test_data_25x.fa | 50 ----- data/sars-cov-2/sars-cov-2_test_data_50x.fa | 100 ---------- data/sars-cov-2/sars-cov-2_test_data_5x.fa | 10 - 6 files changed, 382 deletions(-) delete mode 100644 data/sars-cov-2/sars-cov-2_test_data_100x.fa delete mode 100644 data/sars-cov-2/sars-cov-2_test_data_10x.fa delete mode 100644 data/sars-cov-2/sars-cov-2_test_data_1x.fa delete mode 100644 data/sars-cov-2/sars-cov-2_test_data_25x.fa delete mode 100644 data/sars-cov-2/sars-cov-2_test_data_50x.fa delete mode 100644 data/sars-cov-2/sars-cov-2_test_data_5x.fa diff --git a/data/sars-cov-2/sars-cov-2_test_data_100x.fa b/data/sars-cov-2/sars-cov-2_test_data_100x.fa deleted file mode 100644 index b4d730fd..00000000 --- a/data/sars-cov-2/sars-cov-2_test_data_100x.fa +++ /dev/null @@ -1,200 +0,0 @@ ->hCoV-19/Canada/ON-SLB3081/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3139/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3086/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00408926001/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00245966/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-UHTC_0450/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTTGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCAAAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTGTACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAATCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAATATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACTGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGTCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGTCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTTTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCTCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAACAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nDJXQ-Q8150877C2/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-SLB3103/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3141/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACATTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTAYCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3105/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGATTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3076/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3167/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTTAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGYTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTCCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTTTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGATAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nIUM-U0182948/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAATCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACTAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCNNNNNNTTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACTTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACGTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATTTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTATTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAATCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTATTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAGATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGATTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGATATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTTTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATCCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTCTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATCTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGACTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00368847001A/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCTGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAGCAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTTCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATTAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCATTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGTGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCGTATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTTGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00596829001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATTAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAGACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTACGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTGTTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00611875001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTCGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTTAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTTTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTATAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACCGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACATTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCACTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGTTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCGTTTGGAATCTTGATTATATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAATTCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTATAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGTTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00609962001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGTTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTTTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGAAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTTAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTAGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATTTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGGAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATTCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTATCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCCACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAGCATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCATATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAGAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCGAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACGAAAACAACAAAAGTCGGATGGAAAGTGAGTTAAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTTTTATGGACCTTGAAGGAAAACAGGGTGATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTGTTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAAGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTAGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTCTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCAGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGTTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTTTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCATTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3121/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACAYCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCNCCTAATATGATGGTAACAAACAATACCTTCAYACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTNNNNNNNNNNNNNNNNNNNNNNNNNNTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAARGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCTTGCATACACTMATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTANNNNNNNNGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTNNNNACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGAGCCTGAAGAACATGTCCAAATTCACACAATNNACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nIID-V0183354/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGATCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTATTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTNTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAAGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTTGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTTGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGTCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGTGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCTCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTTGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTTAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00384111001/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTATTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAATAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAATACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAATTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGGATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-1nSKP-0636208995/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGNCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAGGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNNNGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGNNGCTGTAGACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTGAAATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTTGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00567417001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAATTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAAATCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAANTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACTTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGTTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACTATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATTCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCTGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGGTTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGACTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTCAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nDJXQ-Q8020395/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTCTTGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTTAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAATCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAATGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAAAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACTCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTTCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGTTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTGTTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAATAAAGGGCGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGATTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTTTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTTTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGCAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAACAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCGCTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGTGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGGCCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAACCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCTCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00414073001/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAATAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGTATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAAGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGACGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACTACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTTTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAATTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACAGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGSGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACGAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGTTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAATTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGATACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGGCTTTAGCTTGTGGGTTTACAAACAATTTGATATTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATANNNNNNCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGTAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAAAAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGTAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACGCGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTATTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTACTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGTGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAGGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCATATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00345776001/2021 -AGATCTATTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGACGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTGCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACGTTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTTGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAATTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACTCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTACGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCGAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTTAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATKACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAATAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTTTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACCAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATTTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTRTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCGCTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGTCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTTTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATTAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATACAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00244596/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTATGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATTC ->hCoV-19/Canada/QC-JUS-V6011941/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-UHTC_0418/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00466204001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTTACCTGTGCAAAGGAAATTAATGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAATCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTNNCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0435/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATTTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTATATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN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TTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0480/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGNTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00501697001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTACTGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAATTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATATAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTCGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACTAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCTATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAAGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0437/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0463/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGTTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATTCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTNCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATAGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGGTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCTTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-JUS-V5290830/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTYGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTTATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-UHTC_0458/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACCGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0456/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0451/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTTTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00500193001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAAATCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATNNNNNNNNNNNNNNNNNNGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATAGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGTTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTACAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCATCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0415/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAATGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAATTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGATGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAACACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACGTGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTATACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAATAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTACATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCCTTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGTTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTTTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCTATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCATTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTATTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACTAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCTAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0484/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTGTTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAGACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTTGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTCTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAATACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGTAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTATGAAGTATTTTGTGAAAATAGGACCTGAGTGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCTTTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCTAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTATTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0462/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTATCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nIEOQ-S8098799/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAATGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAATAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-UHTC_0481/2021 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CTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0423/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/Qc-HSJ-T8074357/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAATAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-UHTC_0464/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCCACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00369301001/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATTCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGACTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATTTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATTGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATTTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAATTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCACACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGTTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAANCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAACCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTTCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTTAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTTCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGTTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00537936001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCGCATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTAAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGTTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAATAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAATTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGGCTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00338868001/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCATCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCGGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGCGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGTTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAATAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTACTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAA ->hCoV-19/Canada/QC-L00555756001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAACAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAGTTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAATATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATYTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACACTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-CHUM-2007801609A/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTACCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTNNNNNNNNNNNNNGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00532342001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGATACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTANNTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATTTTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-CHUS-473818731/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTTCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATAGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGTCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTTTAACATAATAGGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTTTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTTGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTTATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTTAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-LSPQ-L00584454001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGTTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAATATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTATAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACATAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTWTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGTGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGCTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATNNNNNTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCTAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTTAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0488/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00656639001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTTAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATGGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGATATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCAGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTGGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCGGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCATACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGTAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGTTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAGACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCAACAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCATCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGAAACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTACTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGCTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAACCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAGCATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGATAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCCCATGTGATTTTAATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00538903001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGTAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTTAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATTTTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00528329001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACAGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGTATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGTATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAATAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTGAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAATTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nDJXP-8143490664/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCKTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAATATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGATACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTTCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATTCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCTCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCTAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGMAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAATGAAAATGGANNNATTACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACATACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAGGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATTAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-1nDJLG-R4162282/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGTTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACTCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTTCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATTTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATAGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAATCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCTCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGGTATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTTAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACACAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00612192001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGTGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGTTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAATATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATTTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATTGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACATAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTATAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGTGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTGGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGCTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACATTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCTAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTTAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nDJXW-511485281/2022 -TTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAGGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCGGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATATAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTACTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTCAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGTTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTGTTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTCACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAATATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGTTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCATTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTATAGTGCGTGAGCCAGAAGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATCTCGCACCATTTTTCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATAGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAAAAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTANNTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAAAGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCTTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTTTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGGTTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCCAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGGTCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTA ->hCoV-19/Canada/QC-1nDJXP-8143732050/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATATACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGAAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAATATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGATACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATTCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCTCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCTAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTGTCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATNNNNTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTANTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGTTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACATACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAGGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATTAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00622377001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATCGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATTATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTGGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTTTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGAAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTTAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATTTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATTCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACCATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACATCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAGCATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCATATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCGAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACGAAAACAACAAAAGTCGGATGGAAAGTGAGTTAAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTGTTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAAGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTAGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTCTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAACCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACCCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCCCATGTGATTTTAATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00484774001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACCTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAGCTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTTTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATTAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0471/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCTTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00504249001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNCGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCNNNNTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAACGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATGAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTATTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGCAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTGAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCAGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTTAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACTCAGGTTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCTCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nDJXQ-2032905072A/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGATTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGGTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00499441001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTGTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGTAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCTAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00338802001/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGCTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAAGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTTATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTTAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAA ->hCoV-19/Canada/QC-L00370688001/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCATATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGTCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAACCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACTTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAATTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGATTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTTTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTTTGACCAGACCGCTTCTAGAAAGTGAACTAGTAATCGGAGCTGTCATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGTTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGATGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00492179001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTATCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTATAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00508517001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTTGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGACCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGTATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTWTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGTATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAATAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCTTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nIEOQ-U40633579Q/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAATATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGATACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATTCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCTCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCTAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACATACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAGGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATTAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-1nMCY-T0161612/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTCGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCTTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAATCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTCTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACTAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGGAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTGGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGTCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTATGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACAACACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCATTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACCTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTATTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACACGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGACGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGACACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTNNNNNNNNATTACCACAAAAACAACAAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAGCCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAAGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTTCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGTAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTTCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTTCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTCACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTATAATGTCTGATAATGGACTCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGATGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTTAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCATCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACTGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00559276001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAACCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAGTTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTTGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAACTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nDJXQ-Q8251693C2/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTATTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCTAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCATGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACGGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGTTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCACACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCCTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-1nKWV-W9062318/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATNNNNNNCCTNNNNNTNNNNNNNNNNNNNNNGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGNTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTYTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTTTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTTATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00367589001/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTTTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCATACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGTTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGATATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATTTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCCCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAANTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTTGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCTTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCATGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTCTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTTTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATATTAATTGTTATGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACACGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTTAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACCCAGGCCTAAACTCATGCATACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00609385001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGATGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGGGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTAAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGGTGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCTTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGCTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTGCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAATGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGGTATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00521508001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTTCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTGTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTTTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTTGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGTAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCTAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nIOU-A4182885/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACGCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCTTTGCACCCAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACATGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCTACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAATAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACTTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGATTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGACGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGTAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGTCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTTATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTTCTAGAATCGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00537408001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGCTGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTNGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAGTTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACTTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCATACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTATTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCTTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATTTTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nDWVQ-MX21186518/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATTGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTATAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCATATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGATACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-LSPQ-L00584154001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCTTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAATTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAAACACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACTAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAATTTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCRCACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00577502001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGGGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTATTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAGTTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGATTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAATTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00597644001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGATAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTAGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATTTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTATAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGCGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGGTTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCATCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCGAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGTTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTGTTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGTACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00567252001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTTGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGCGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCATCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAACGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCTTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGNNNCTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACNNNGCTTAAAAAGTGTAAAAGTGCNTTTTACNNNNNNNNNNNNATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATTCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTGGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTCGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAATCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTTACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACCGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00394372001/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGTACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCATCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTGTTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCGAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGAATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTGCAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAATCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCTTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTCGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACACCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATTATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00488234001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGTTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTATTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGGGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTATTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTWTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTATATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCAGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTTAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAGTTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTTATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00504857001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAGGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGACTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTATAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTTTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCATGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nIOU-A4293969/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACGCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCCAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACATGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGNNNNNNNNAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTTGGTTTTTACTATTAAGTGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCTACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAATAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACTTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGATTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATTACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGACGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGTAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGTCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTTATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATCGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGC ->hCoV-19/Canada/QC-L00610702001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAATATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTCTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTGTGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCTATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTGGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTCTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTTATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCATACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00378724001/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATTGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGATTACTACCACACAACTGATCTTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACGCTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTTTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGTTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGCTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAATTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAATAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTTTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGTTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTATAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCTTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGTTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-1nDJXW-505000201/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTATAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAATGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTATACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACNNTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAAGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAGCTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAATCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAATAAGCTTTGTGAAGAAATGCTGTACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTGTACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACTTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATTACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTGACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATTAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACTCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTTGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00482194001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTATTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGACCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTWTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGATTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGATTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCAGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTTAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACATCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00450298001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATATTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCTGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAACTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00576722001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGCACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATCTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATTTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTATTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAACATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATACCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAATCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTCAGACGCTGATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAACTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTTCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGATGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00501172001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAAGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTAATGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATATACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN diff --git a/data/sars-cov-2/sars-cov-2_test_data_10x.fa b/data/sars-cov-2/sars-cov-2_test_data_10x.fa deleted file mode 100644 index 84f3148e..00000000 --- a/data/sars-cov-2/sars-cov-2_test_data_10x.fa +++ /dev/null @@ -1,20 +0,0 @@ ->hCoV-19/Canada/ON-SLB3081/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3139/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3086/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00408926001/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00245966/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-UHTC_0450/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTTGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCAAAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTGTACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAATCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAATATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACTGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGTCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGTCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTTTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCTCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAACAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nDJXQ-Q8150877C2/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-SLB3103/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3141/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACATTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTAYCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3105/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGATTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN diff --git a/data/sars-cov-2/sars-cov-2_test_data_1x.fa b/data/sars-cov-2/sars-cov-2_test_data_1x.fa deleted file mode 100644 index c641227d..00000000 --- a/data/sars-cov-2/sars-cov-2_test_data_1x.fa +++ /dev/null @@ -1,2 +0,0 @@ ->hCoV-19/Canada/ON-SLB3081/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN diff --git a/data/sars-cov-2/sars-cov-2_test_data_25x.fa b/data/sars-cov-2/sars-cov-2_test_data_25x.fa deleted file mode 100644 index ec826315..00000000 --- a/data/sars-cov-2/sars-cov-2_test_data_25x.fa +++ /dev/null @@ -1,50 +0,0 @@ ->hCoV-19/Canada/ON-SLB3081/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3139/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3086/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00408926001/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00245966/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-UHTC_0450/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTTGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCAAAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTGTACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAATCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAATATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACTGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGTCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGTCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTTTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCTCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAACAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nDJXQ-Q8150877C2/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-SLB3103/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3141/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACATTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTAYCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3105/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGATTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3076/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3167/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTTAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGYTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTCCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTTTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGATAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nIUM-U0182948/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAATCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACTAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCNNNNNNTTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACTTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACGTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATTTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTATTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAATCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTATTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAGATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGATTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGATATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTTTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATCCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTCTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATCTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGACTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00368847001A/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCTGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAGCAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTTCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATTAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCATTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGTGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCGTATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTTGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00596829001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATTAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAGACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTACGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTGTTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00611875001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTCGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTTAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTTTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTATAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACCGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACATTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCACTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGTTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCGTTTGGAATCTTGATTATATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAATTCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTATAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGTTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00609962001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGTTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTTTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGAAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTTAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTAGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATTTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGGAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATTCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTATCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCCACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAGCATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCATATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAGAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCGAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACGAAAACAACAAAAGTCGGATGGAAAGTGAGTTAAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTTTTATGGACCTTGAAGGAAAACAGGGTGATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTGTTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAAGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTAGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTCTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCAGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGTTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTTTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCATTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3121/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACAYCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCNCCTAATATGATGGTAACAAACAATACCTTCAYACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTNNNNNNNNNNNNNNNNNNNNNNNNNNTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAARGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCTTGCATACACTMATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTANNNNNNNNGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTNNNNACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGAGCCTGAAGAACATGTCCAAATTCACACAATNNACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nIID-V0183354/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGATCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTATTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTNTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAAGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTTGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTTGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGTCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGTGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCTCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTTGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTTAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00384111001/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTATTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAATAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAATACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAATTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGGATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-1nSKP-0636208995/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGNCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAGGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNNNGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGNNGCTGTAGACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTGAAATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTTGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00567417001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAATTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAAATCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAANTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACTTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGTTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACTATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATTCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCTGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGGTTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGACTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTCAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nDJXQ-Q8020395/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTCTTGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTTAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAATCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAATGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAAAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACTCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTTCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGTTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTGTTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAATAAAGGGCGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGATTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTTTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTTTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGCAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAACAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCGCTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGTGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGGCCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAACCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCTCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00414073001/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAATAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGTATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAAGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGACGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACTACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTTTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAATTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACAGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGSGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACGAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGTTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAATTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGATACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGGCTTTAGCTTGTGGGTTTACAAACAATTTGATATTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATANNNNNNCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGTAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAAAAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGTAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACGCGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTATTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTACTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGTGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAGGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCATATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00345776001/2021 -AGATCTATTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGACGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTGCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACGTTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTTGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAATTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACTCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTACGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCGAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTTAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATKACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAATAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTTTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACCAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATTTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTRTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCGCTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGTCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTTTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATTAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATACAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC diff --git a/data/sars-cov-2/sars-cov-2_test_data_50x.fa b/data/sars-cov-2/sars-cov-2_test_data_50x.fa deleted file mode 100644 index aee72a4d..00000000 --- a/data/sars-cov-2/sars-cov-2_test_data_50x.fa +++ /dev/null @@ -1,100 +0,0 @@ ->hCoV-19/Canada/ON-SLB3081/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3139/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3086/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00408926001/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00245966/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-UHTC_0450/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTTGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCAAAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTGTACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAATCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAATATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACTGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGTCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGTCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTTTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCTCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAACAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nDJXQ-Q8150877C2/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTATTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTTTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTGGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAACAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGATAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATTTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGTAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTTAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAATGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-SLB3103/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3141/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACATTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTAYCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3105/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGATTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3076/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3167/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTTAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGYTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTCCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTTTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGATAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nIUM-U0182948/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAATCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACTAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCNNNNNNTTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACTTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACGTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATTTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTATTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAATCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTATTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAGATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGATTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGATATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTTTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATCCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTCTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATCTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGACTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00368847001A/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCTGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAGCAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTTCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATTAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCATTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGTGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCGTATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTTGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00596829001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATTAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAGACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTCAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTACGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTGTTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00611875001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAGAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTCGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTTAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTTTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTATAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTTAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGACCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATACCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACCGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACATTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCCCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATACGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCGGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGCCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCACTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTACCAAAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAAGAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGAGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGTTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCATATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGCCTAGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTCCTAATTGTTACTCTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCGTTTGGAATCTTGATTATATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTATGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAATTCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTATAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATTCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGTTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00609962001/2023 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGTTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTTTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGAAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTTAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTAGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATTTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGGAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATTCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTATCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCCACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAGCATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCATATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAGAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCGAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACGAAAACAACAAAAGTCGGATGGAAAGTGAGTTAAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTTTTATGGACCTTGAAGGAAAACAGGGTGATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTGTTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAAGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTCATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTACGGTTAGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAAGCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTCTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCATGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCAGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTTACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGTTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTGCGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTTTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCATTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3121/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACAYCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCNCCTAATATGATGGTAACAAACAATACCTTCAYACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTNNNNNNNNNNNNNNNNNNNNNNNNNNTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAARGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCTTGCATACACTMATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTANNNNNNNNGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTNNNNACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGAGCCTGAAGAACATGTCCAAATTCACACAATNNACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nIID-V0183354/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGATCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTATTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTNTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAAGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTTGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTTGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGTCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGTGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCTCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTTGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTTAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00384111001/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTATTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAATAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAATACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAATTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATCAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGGATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGCACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-1nSKP-0636208995/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGNCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAGGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTNNNNNNNNNNNNNNNNNNGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGNNGCTGTAGACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTGAAATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTTGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00567417001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAATTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTTCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAAATCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAANTAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACTTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGTTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGAGGGGTGTCATGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACTATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCACATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATTCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCTGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGGTTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACGTCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGACTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTCAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGGCCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nDJXQ-Q8020395/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTCTTGTCCGTGTTGCAGCCGATTATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTTAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAATCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAATGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAAAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACTCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTTCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGTTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTGTTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAATAAAGGGCGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGATTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTTTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTTTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGCAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAACAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCGCTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGTGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGGCCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAACCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCTCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00414073001/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAATAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGTATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAAGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGACGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACTACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTTTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAATTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACAGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGSGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACGAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGTTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAATTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGATACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGGCTTTAGCTTGTGGGTTTACAAACAATTTGATATTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATANNNNNNCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGTAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAAAAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGTAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACGCGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTATTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTACTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGTGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAGGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCATATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00345776001/2021 -AGATCTATTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGACGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTGCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACGTTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTTGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAATTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACTCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTACGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCGAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTTAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATKACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAATAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTTTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACCAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATTTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTRTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCGCTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGTCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTTTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATTAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCATCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATACAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00244596/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTATGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATTC ->hCoV-19/Canada/QC-JUS-V6011941/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-UHTC_0418/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00466204001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTTACCTGTGCAAAGGAAATTAATGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAATCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTTTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTNNCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTTTTAATTGTTACTTTCCTTTACGATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTTAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGCGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTCTCTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0435/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATTTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTATATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN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TTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0480/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGNTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00501697001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTACTGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAATTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATATAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTCGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACTAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCTATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAAGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0437/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTTTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTTTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCATGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGTTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTTTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGTTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGATATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCTAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTTTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGATTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATTTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAATATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0463/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGTTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATTCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTNCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATAGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGGTTTATAAGGGTGTTATCATGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCTTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-JUS-V5290830/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTYGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTTATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-UHTC_0458/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACCGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0456/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0451/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTTTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00500193001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAAATCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTAAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATNNNNNNNNNNNNNNNNNNGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATAGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGTTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTACAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCATCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0415/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAATGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAATTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGATGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAACACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACGTGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAATTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTATACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAATAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTACATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCCTTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGTTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTTTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCTATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCATTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTATTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACTAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCTAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0484/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTGTTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAGACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTTGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTCTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAATACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGTAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTATGAAGTATTTTGTGAAAATAGGACCTGAGTGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCTTTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCTAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTATTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0462/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTATCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-1nIEOQ-S8098799/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAATGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTTTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAATAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-UHTC_0481/2021 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CTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-UHTC_0423/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGCTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACGTAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCATTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTTTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATTGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTNNTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACTTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACATATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATCGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAATGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGATCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTATATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTTTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTTAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGTAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/Qc-HSJ-T8074357/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGACGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTTTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAATTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAATGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCCTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTTCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCGCATACAGTGATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGCGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTTCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAATCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAAAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCATATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATAGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGTTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTTTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAATAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/ON-UHTC_0464/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCNNAAAAGAGAAAGTCAACATCAATATTGTTGTTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATTTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCCACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTTTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTATTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTATAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCNNTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATTGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTATAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGACCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATTTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00369301001/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATTCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGACTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATTTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTATTACCACAAAAACAACAAAAGTTGGATTGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATTTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAATTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCACACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGTTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAANCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAACCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTTCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTTAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTTCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACNNAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGTTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC ->hCoV-19/Canada/QC-L00537936001/2022 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGGTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCATTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCGCATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTAGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCTTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTAAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTGGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCATTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGATATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGACACAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAACAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATTTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTTTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGTTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTATGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACGTACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAATTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAGGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTATAACCAGAACTCAATCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGATGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGGGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGATGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTTCGCACCATTTTTCGCTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTAATGAAGTCAGCCAAATCGCTCCAGGGCAAACTGGAAATATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAAGCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAACAAACCTTGTAATGGTGTTGCAGGTGTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCGACCCACTTATGGTGTTGGTCACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAATATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAAGTCTCATCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAAACGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCATAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAAATTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAATAACACAGTTTATGATCCTTTGCAACCTGAATTAGATTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACTCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACATTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGATAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAAATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAAGAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAACTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAATTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGGCTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGCGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGTTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAATGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACTCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCCGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATTTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00338868001/2021 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCTGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTATTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCATCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGATAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTTACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTACAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCGGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCTGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCATCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGATGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACCTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAGGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAGGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTTATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGATGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGCGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCATCGGCGGGCACGTAGTGTAGTTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCATAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTGCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACACACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAATAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTACTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTTAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTATAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTGCATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAATGTCTCTAAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTTTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAA diff --git a/data/sars-cov-2/sars-cov-2_test_data_5x.fa b/data/sars-cov-2/sars-cov-2_test_data_5x.fa deleted file mode 100644 index d59fc34c..00000000 --- a/data/sars-cov-2/sars-cov-2_test_data_5x.fa +++ /dev/null @@ -1,10 +0,0 @@ ->hCoV-19/Canada/ON-SLB3081/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGAYGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTTATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAAACGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3139/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCGGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/ON-SLB3086/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTATAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTYAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGAYATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCATACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCATAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00408926001/2021 -NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTTTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCCATTGGTTGGTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAGGCGGTGCACCAACAAAGGTTACTTTTGGTGATGACACTGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGTCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACTAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATATCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATTAAAACTTATAGAGTACACTGATTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCATTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGTCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAACAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAATCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCGCTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTGGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAACATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCAGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACTACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTGGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGTTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTGGTTGTGATGGTGGCAGTTTGTATGTAAATAAACATGCATTCCACACACCAGCTTTTGATAAAAGTGCTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATGGAAAACAAGTAGTGTCAGATATAGATTATGTACCACTAAAGTCTGCTACGTGTATAACACGTTGCAATTTAGGTGGTGCTGTCTGTAGACATCATGCTAATGAGTACAGATTGTATCTCGATGCTTATAACATGATGATCTCAGCTGGCTTTAGCTTGTGGGTTTACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTAGAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGRTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCGGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCAAACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCGTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAAATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTTTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAACTTTGAAGCAAGGTGAAATCAAGGATGCTATTCCTTTAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTACCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGCTTCACCTAAACTGTTCATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGATAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAATTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAATCTAAACGAACAAACTAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGGCCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTATGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCTGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTTGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTTATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACTCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN ->hCoV-19/Canada/QC-L00245966/2020 -AGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAACATCTTAAAGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTGGTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTAAAGCTTCATGCACTTTGTCCGAACAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTGCCGTGAACATGAGCATGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACACCTTCAATGGGGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGTAAGGGTGGTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTGCTGACTCTATCATTATTGGTGGAGCTAAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGGGAGAAACACTTCCCACAGAAGTGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACANNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNGTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTGCCTATACANNTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTATCTGAATTACTTACACCACTGGGCATTGATTTAGATGAGTGGAGTATGGCTACATACTACTTATTTGATGAGTCTGGTGAGTTTAAATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAGGTGATTGTGAAGAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTGGAATTTGGTGCCACTTCTGCTGCTCTTCAACCTGAAGAAGAGCAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAACAAGACGGCAGTGAGGACAATCAGACAACTACTATTCAAACAATTGTTGAGGTTCAACCTCAATTAGAGATGGAACTTACACCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGACATTGTGGAAGAAGCTAAAAAGGTAAAACCAACAGTGGTTGTTAATGCAGCCAATGTTTACCTTAAACATGGAGGAGGTGTTGCAGGAGCCTTAAATAAGGCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTTAAAGTGGGTGGTAGTTGTGTTTTAAGCGGACACAATCTTGCTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAGCACGAAGTTCTACTTGCACCATTATTATCAGCTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGTCTTTGATAAAAATCTCTATGACAAACTTGTTTCAAGCTTTTTGGAAATGAAGAGTGAAAAGCAAGTTGAACAAAAGATCGCTGAGATTCCTAAAGAGGAAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAGAGAAAACAAGATGATAAGAAAATCAAAGCTTGTGTTGAAGAAGTTACAACAACTCTGGAAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATTCTGCCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATGCTCCATATATAGTGGGTGATGTTGTTCAAGAGGGTGTTTTAACTGCTGTGGTTATACCTACTAAAAAGGCTGGTGGCACTACTGAAATGCTAGCGAAAGCTTTGAGAAAAGTGCCAACAGACAATTATATAACCACTTACCCGGGTCAGGGTTTAAATGGTTACACTGTAGAGGAGGCAAAGACAGTGCTTAAAAAGTGTAAAAGTGCCTTTTACATTCTACCATCTATTATCTCTAATGAGAAGCAAGAAATTCTTGGAACTGTTTCTTGGAATTTGCGAGAAATGCTTGCACATGCAGAAGAAACACGCAAATTAATGCCTGTCTGTGTGGAAACTAAAGCCATAGTTTCAACTATACAGCGTAAATATAAGGGTATTAAAATACAAGAGGGTGTGGTTGATTATGGTGCTAGATTTTACTTTTACACCAGTAAAACAACTGTAGCGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAATGCCACTTGGCTATGTAACACATGGCTTAAATTTGGAAGAAGCTGCTCGGTATATGAGATCTCTCAAAGTGCCAGCTACAGTTTCTGTTTCTTCACCTGATGCTGTTACAGCGTATAATGGTTATCTTACTTCTTCTTCTAAAACACCTGAAGAACATTTTATTGAAACCATCTCACTTGCTGGTTCCTATAAAGATTGGTCCTATTCTGGACAATCTACACAACTAGGTATAGAATTTCTTAAGAGAGGTGATAAAAGTGTATATTACACTAGTAATCCTACCACATTCCACCTAGATGGTGAAGTTATCACCTTTGACAATCTTAAGACACTTCTTTCTTTGAGAGAAGTGAGGACTATTAAGGTGTTTACAACAGTAGACAACATTAACCTCCACACGCAAGTTGTGGACATGTCAATGACATATGGACAACAGTTTGGTCCAACTTATTTGGATGGAGCTGATGTTACTAAAATAAAACCTCATAATTCACATGAAGGTAAAACATTTTATGTTTTACCTAATGATGACACTCTACGTGTTGAGGCTTTTGAGTACTACCACACAACTGATCCTAGTTTTCTGGGTAGGTACATGTCAGCATTAAATCACACTAAAAAGTGGAAATACCCACAAGTTAATGGTTTAACTTCTATTAAATGGGCAGATAACAACTGTTATCTTGCCACTGCATTGTTAACACTCCAACAAATAGAGTTGAAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAGAGCAAGGGCTGGTGAAGCTGCTAACTTTTGTGCACTTATCTTAGCCTACTGTAATAAGACAGTAGGTGAGTTAGGTGATGTTAGAGAAACAATGAGTTACTTGTTTCAACATGCCAATTTAGATTCTTGCAAAAGAGTCTTGAACGTGGTGTGTAAAACTTGTGGACAACAGCAGACAACCCTTAAGGGTGTAGAAGCTGTTATGTACATGGGCACACTTTCTTATGAACAATTTAAGAAAGGTGTTCAGATACCTTGTACGTGTGGTAAACAAGCTACAAAATATCTAGTACAACAGGAGTCACCTTTTGTTATGATGTCAGCACCACCTGCTCAGTATGAACTTAAGCATGGTACATTTACTTGTGCTAGTGAGTACACTGGTAATTACCAGTGTGGTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTGCATAGACGGTGCTTTACTTACAAAGTCCTCAGAATACAAAGGTCCTATTACGGATGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTGGATGGTGTTGTTTGTACAGAAATTGACCCTAAGTTGGACAATTATTATAAGAAAGACAATTCTTATTTCACAGAGCAACCAATTGATCTTGTACCAAACCAACCATATCCAAACGCAAGCTTCGATAATTTTAAGTTTGTATGTGATAATATCAAATTTGCTGATGATTTAAACCAGTTAACTGGTTATAAGAAACCTGCTTCAAGAGAGCTTAAAGTTACATTTTTCCCTGACTTAAATGGTGATGTGGTGGCTATTGATTATAAACACTACACACCCTCTTTTAAGAAAGGAGCTAAATTGTTACATAAACCTATTGTTTGGCATGTTAACAATGCAACTAATAAAGCCACGTATAAACCAAATACCTGGTGTATACGTTGTCTTTGGAGCACAAAACCAGTTGAAACATCAAATTCGTTTGATGTACTGAAGTCAGAGGACGCGCAGGGAATGGATAATCTTGCCTGCGAAGATCTAAAACCAGTCTCTGAAGAAGTAGTGGAAAATCCTACCATACAGAAAGACGTTCTTGAGTGTAATGTGAAAACTACCGAAGTTGTAGGAGACATTATACTTAAACCAGCAAATAATAGTTTAAAAATTACAGAAGAGGTTGGCCACACAGATCTAATGGCTGCTTATGTAGACAATTCTAGTCTTACTATTAAGAAACCTAATGAATTATCTAGAGTATTAGGTTTGAAAACCCTTGCTACTCATGGTTTAGCTGCTGTTAATAGTGTCCCTTGGGATACTATAGCTAATTATGCTAAGCCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGGTGTTTAAACCGTGTTTGTACTAATTATATGCCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAGCATCTATGCCGACTACTATAGCAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAGAGGCTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTGGTTTTTACTATTAAGTGTTTGCCTAGGTTCTTTAATCTACTCAACCGCTGCTTTAGGTGTTTTAATGTCTAATTTAGGCATGCCTTCTTACTGTACTGGTTACAGAGAAGGCTATTTGAACTCTACTAATGTCACTATTGCAACCTACTGTACTGGTTCTATACCTTGTAGTGTTTGTCTTAGTGGTTTAGATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTACCATTTCATCTTTTAAATGGGATTTAACTGCTTTTGGCTTAGTTGCAGAGTGGTTTTTGGCATATATTCTTTTCACTAGGTTTTTCTATGTACTTGGATTGGCTGCAATCATGCAATTGTTTTTCAGCTATTTTGCAGTACATTTTATTAGTAATTCTTGGCTTATGTGGTTAATAATTAATCTTGTACAAATGGCCCCGATTTCAGCTATGGTTAGAATGTACATCTTCTTTGCATCATTTTATTATGTATGGAAAAGTTATGTGCATGTTGTAGACGGTTGTAATTCATCAACTTGTATGATGTGTTACAAACGTAATAGAGCAACAAGAGTCGAATGTACAACTATTGTTAATGGTGTTAGAAGGTCCTTTTATGTCTATGCTAATGGAGGTAAAGGCTTTTGCAAACTACACAATTGGAATTGTGTTAATTGTGATACATTCTGTGCTGGTAGTACATTTATTAGTGATGAAGTTGCGAGAGACTTGTCACTACAGTTTAAAAGACCAATAAATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTGAAGAATGGTTCCATCCATCTTTACTTTGATAAAGCTGGTCAAAAGACTTATGAAAGACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTGAGAGCTAATAACACTAAAGGTTCATTGCCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTGCAAAATCAGCGTCTGTTTACTACAGTCAGCTTATGTGTCAACCTATACTGTTACTAGATCAGGCATTAGTGTCTGATGTTGGTGATAGTGCGGAAGTTGCAGTTAAAATGTTTGATGCTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATGGAAAAACTCAAAACACTAGTTGCAACTGCAGAAGCTGAACTTGCAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAGCAGCTCGGCAAGGGTTTGTTGATTCAGATGTAGAAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATCAATCTGACATAGAAGTTACTGGCGATAGTTGTAATAACTATATGCTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTGGTGCTTGTATTGACTGTAGTGCGCGTCATATTAATGCGCAGGTAGCAAAAAGTCACAACATTGCTTTGATATGGAACGTTAAAGATTTCATGTCATTGTCTGAACAACTACGAAAACAAATACGTAGTGCTGCTAAAAAGAATAACTTACCTTTTAAGTTGACATGTGCAACTACTAGACAAGTTGTTAATGTTGTAACAACAAAGATAGCACTTAAGGGTGGTAAAATTGTTAATAATTGGTTGAAGCAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTGCTGCTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTGACTTTTCAAGTGAAATCATAGGATACAAGGCTATTGATGGTGGTGTCACTCGTGACATAGCATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTGACACATGGTTTAGCCAGCGTGGTGGTAGTTATACTAATGACAAAGCTTGCCCATTGATTGCTGCAGTCATAACAAGAGAAGTGGGTTTTGTCGTGCCTGGTTTGCCTGGCACGATATTACGCACAACTAATGGTGACTTTTTGCATTTCTTACCTAGAGTTTTTAGTGCAGTTGGTAACATCTGTTACACACCATCAAAACTTATAGAGTACACTGACTTTGCAACATCAGCTTGTGTTTTGGCTGCTGAATGTACAATTTTTAAAGATGCTTCTGGTAAGCCAGTACCATATTGTTATGATACCAATGTACTAGAAGGTTCTGTTGCTTATGAAAGTTTACGCCCTGACACACGTTATGTGCTCATGGATGGCTCTATTATTCAATTTCCTAACACCTACCTTGAAGGTTCTGTTAGAGTGGTAACAACTTTTGATTCTGAGTACTGTAGGCACGGCACTTGTGAAAGATCAGAAGCTGGTGTTTGTGTATCTACTAGTGGTAGATGGGTACTTAACAATGATTATTACAGATCTTTACCAGGAGTTTTCTGTGGTGTAGATGCTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTGGTGCTTTGGACATATCAGCATCTATAGTAGCTGGTGGTATTGTAGCTATCGTAGTAACATGCCTTGCCTACTATTTTATGAGGTTTAGAAGAGCTTTTGGTGAATACAGTCATGTAGTTGCCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTGGTGTTTATTCTGTTATTTACTTGTACTTGACATTTTATCTTACTAATGATGTTTCTTTTTTAGCACATATTCAGTGGATGGTTATGTTCACACCTTTAGTACCTTTCTGGATAACAATTGCTTATATCATTTGTATTTCCACAAAGCATTTCTATTGGTTCTTTAGTAATTACCTAAAGAGACGTGTAGTCTTTAATGGTGTTTCCTTTAGTACTTTTGAAGAAGCTGCGCTGTGCACCTTTTTGTTAAATAAAGAAATGTATCTAAAGTTGCGTAGTGATGTGCTATTACCTCTTACGCAATATAATAGATACTTAGCTCTTTATAATAAGTACAAGTATTTTAGTGGAGCAATGGATACAACTAGCTACAGAGAAGCTGCTTGTTGTCATCTCGCAAAGGCTCTCAATGACTTCAGTAACTCAGGTTCTGATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAGCTGTTTTGCAGAGTGGTTTTAGAAAAATGGCATTCCCATCTGGTAAAGTTGAGGGTTGTATGGTACAAGTAACTTGTGGTACAACTACACTTAACGGTCTTTGGCTTGATGACGTAGTTTACTGTCCAAGACATGTGATCTGCACCTCTGAAGACATGCTTAACCCTAATTATGAAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTGGTACAGGCTGGTAATGTTCAACTCAGGGTTATTGGACATTCTATGCAAAATTGTGTACTTAAGCTTAAGGTTGATACAGCCAATCCTAAGACACCTAAGTATAAGTTTGTTCGCATTCAACCAGGACAGACTTTTTCAGTGTTAGCTTGTTACAATGGTTCACCATCTGGTGTTTACCAATGTGCTATGAGGCCCAATTTCACTATTAAGGGTTCATTCCTTAATGGTTCATGTGGTAGTGTTGGTTTTAACATAGATTATGACTGTGTCTCTTTTTGTTACATGCACCATATGGAATTACCAACTGGAGTTCATGCTGGCACAGACTTAGAAGGTAACTTTTATGGACCTTTTGTTGACAGGCAAACAGCACAAGCAGCTGGTACGGACACAACTATTACAGTTAATGTTTTAGCTTGGTTGTACGCTGCTGTTATAAATGGAGACAGGTGGTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTGGCTATGAAGTACAATTATGAACCTCTAACACAAGACCATGTTGACATACTAGGACCTCTTTCTGCTCAAACTGGAATTGCCGTTTTAGATATGTGTGCTTCATTAAAAGAATTACTGCAAAATGGTATGAATGGACGTACCATATTGGGTAGTGCTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATGCTCAGGTGTTACTTTCCAAAGTGCAGTGAAAAGAACAATCAAGGGTACACACCACTGGTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAGAGTACTCAATGGTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTGCTATGGGTATTATTGCTATGTCTGCTTTTGCAATGATGTTTGTCAAACATAAGCATGCATTTCTCTGTTTGTTTTTGTTACCTTCTCTTGCCACTGTAGCTTATTTTAATATGGTCTATATGCCTGCTAGTTGGGTGATGCGTATTATGACATGGTTGGATATGGTTGATACTAGTTTGTCTGGTTTTAAGCTAAAAGACTGTGTTATGTATGCATCAGCTGTAGTGTTACTAATCCTTATGACAGCAAGAACTGTGTATGATGATGGTGCTAGGAGAGTGTGGACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATGGTAATGCTTTAGATCAAGCCATTTCCATGTGGGCTCTTATAATCTCTGTTACTTCTAACTACTCAGGTGTAGTTACAACTGTCATGTTTTTGGCCAGAGGTATTGTTTTTATGTGTGTTGAGTATTGCCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAGGCTATTTTTGTACTTGTTACTTTGGCCTCTTTTGTTTACTCAACCGCTACTTTAGACTGACTCTTGGTGTTTATGATTACTTAGTTTCTACACAGGAGTTTAGATATATGAATTCACAGGGACTACTCCCACCCAAGAATAGCATAGATGCCTTCAAACTCAACATTAAATTGTTGGGTGTTGGTGGCAAACCTTGTATCAAAGTAGCCACTGTACAGTCTAAAATGTCAGATGTAAAGTGCACATCAGTAGTCTTACTCTCAGTTTTGCAACAACTCAGAGTAGAATCATCATCTAAATTGTGGGCTCAATGTGTCCAGTTACACAATGACATTCTCTTAGCTAAAGATACTACTGAAGCCTTTGAAAAAATGGTTTCACTACTTTCTGTTTTGCTTTCCATGCAGGGTGCTGTAGACATAAACAAGCTTTGTGAAGAAATGCTGGACAACAGGGCAACCTTACAAGCTATAGCCTCAGAGTTTAGTTCCCTTCCATCATATGCAGCTTTTGCTACTGCTCAAGAAGCTTATGAGCAGGCTGTTGCTAATGGTGATTCTGAAGTTGTTCTTAAAAAGTTGAAGAAGTCTTTGAATGTGGCTAAATCTGAATTTGACCGTGATGCAGCCATGCAACGTAAGTTGGAAAAGATGGCTGATCAAGCTATGACCCAAATGTATAAACAGGCTAGATCTGAGGACAAGAGGGCAAAAGTTACTAGTGCTATGCAGACAATGCTTTTCACTATGCTTAGAAAGTTGGATAATGATGCACTCAACAACATTATCAACAATGCAAGAGATGGTTGTGTTCCCTTGAACATAATACCTCTTACAACAGCAGCCAAACTAATGGTTGTCATACCAGACTATAACACATATAAAAATACGTGTGATGGTACAACATTTACTTATGCATCAGCATTGTGGGAAATCCAACAGGTTGTAGATGCAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTATGGACAATTCACCTAATTTAGCATGGCCTCTTATTGTAACAGCTTTAAGGGCCAATTCTGCTGTCAAATTACAGAATAATGAGCTTAGTCCTGTTGCACTACGACAGATGTCTTGTGCTGCCGGTACTACACAAACTGCTTGCACTGATGACAATGCGTTAGCTTACTACAACACAACAAAGGGAGGTAGGTTTGTACTTGCACTGTTATCCGATTTACAGGATTTGAAATGGGCTAGATTCCCTAAGAGTGATGGAACTGGTACTATCTATACAGAACTGGAACCACCTTGTAGGTTTGTTACAGACACACCTAAAGGTCCTAAAGTGAAGTATTTATACTTTATTAAAGGATTAAACAACCTAAATAGAGGTATGGTACTTGGTAGTTTAGCTGCCACAGTACGTCTACAAGCTGGTAATGCAACAGAAGTGCCTGCCAATTCAACTGTATTATCTTTCTGTGCTTTTGCTGTAGATGCTGCTAAAGCTTACAAAGATTATCTAGCTAGTGGGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTGGTACTGGTCAGGCAATAACAGTTACACCGGAAGCCAATATGGATCAAGAATCCTTTGGTGGTGCATCGTGTTGTCTGTACTGCCGTTGCCACATAGATCATCCAAATCCTAAAGGATTTTGTGACTTAAAAGGTAAGTATGTACAAATACCTACAACTTGTGCTAATGACCCTGTGGGTTTTACACTTAAAAACACAGTCTGTACCGTCTGCGGTATGTGGAAAGGTTATGGCTGTAGTTGTGATCAACTCCGCGAACCCATGCTTCAGTCAGCTGATGCACAATCGTTTTTAAACGGGTTTGCGGTGTAAGTGCAGCCCGTCTTACACCGTGCGGCACAGGCACTAGTACTGATGTCGTATACAGGGCTTTTGACATCTACAATGATAAAGTAGCTGGTTTTGCTAAATTCCTAAAAACTAATTGTTGTCGCTTCCAAGAAAAGGACGAAGATGACAATTTAATTGATTCTTACTTTGTAGTTAAGAGACACACTTTCTCTAACTACCAACATGAAGAAACAATTTATAATTTACTTAAGGATTGTCCAGCTGTTGCTAAACATGACTTCTTTAAGTTTAGAATAGACGGTGACATGGTACCACATATATCACGTCAACGTCTTACTAAATACACAATGGCAGACCTCGTCTATGCTTTAAGGCATTTTGATGAAGGTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTCAATAAAAAGGACTGGTATGATTTTGTAGAAAACCCAGATATATTACGCGTATACGCCAACTTAGGTGAACGTGTACGCCAAGCTTTGTTAAAAACAGTACAATTCTGTGATGCCATGCGAAATGCTGGTATTGTTGGTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTGGTATGATTTCGGTGATTTCATACAAACCACGCCAGGTAGTGGAGTTCCTGTTGTAGATTCTTATTATTCATTGTTAATGCCTATATTAACCTTGACCAGGGCTTTAACTGCAGAGTCACATGTTGACACTGACTTAACAAAGCCTTACATTAAGTGGGATTTGTTAAAATATGACTTCACGGAAGAGAGGTTAAAACTCTTTGACCGTTATTTTAAATATTGGGATCAGACATACCACCCAAATTGTGTTAACTGTTTGGATGACAGATGCATTCTGCATTGTGCAAACTTTAATGTTTTATTCTCTACAGTGTTCCCACTTACAAGTTTTGGACCACTAGTGAGAAAAATATTTGTTGATGGTGTTCCATTTGTAGTTTCAACTGGATACCACTTCAGAGAGCTAGGTGTTGTACATAATCAGGATGTAAACTTACATAGCTCTAGACTTAGTTTTAAGGAATTACTTGTGTATGCTGCTGACCCTGCTATGCACGCTGCTTCTGGTAATCTATTACTAGATAAACGCACTACGTGCTTTTCAGTAGCTGCACTTACTAACAATGTTGCTTTTCAAACTGTCAAACCCGGTAATTTTAACAAAGACTTCTATGACTTTGCTGTGTCTAAGGGTTTCTTTAAGGAAGGAAGTTCTGTTGAATTAAAACACTTCTTCTTTGCTCAGGATGGTAATGCTGCTATCAGCGATTATGACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACGATGGTGGCTGTATTAATGCTAACCAAGTCATCGTCAACAACCTAGACAAATCAGCTGGTTTTCCATTTAATAAATGGGGTAAGGCTAGACTTTATTATGATTCAATGAGTTATGAGGATCAAGATGCACTTTTCGCATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATGCCATTAGTGCAAAGAATAGAGCTCGCACCGTAGCTGGTGTCTCTATCTGTAGTACTATGACCAATAGACAGTTTCATCAAAAATTATTGAAATCAATAGCCGCCACTAGAGGAGCTACTGTAGTAATTGGAACAAGCAAATTCTATGGTGGTTGGCACAACATGTTAAAAACTGTTTATAGTGATGTAGAAAACCCTCACCTTATGGGTTGGGATTATCCTAAATGTGATAGAGCCATGCCTAATATGCTTAGAATTATGGCCTCACTTGTTCTTGCTCGCAAACATACAACGTGTTGTAGCTTGTCACACCGTTTCTATAGATTAGCTAATGAGTGTGCTCAAGTATTGAGTGAAATGGTCATGTGTGGCGGTTCACTATATGTTAAACCAGGTGGAACCTCATCAGGAGATGCCACAACTGCTTATGCTAATAGTGTTTTTAACATTTGTCAAGCTGTCACGGCCAATGTTAATGCACTTTTATCTACTGATGGTAACAAAATTGCCGATAAGTATGTCCGCAATTTACAACACAGACTTTATGAGTGTCTCTATAGAAATAGAGATGTTGACACAGACTTTGTGAATGAGTTTTACGCATATTTGCGTAAACATTTCTCAATGATGATACTCTCTGACGATGCTGTTGTGTGTTTCAATAGCACTTATGCATCTCAAGGTCTAGTGGCTAGCATAAAGAACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAGCAAAATGTTGGACTGAGACTGACCTTACTAAAGGACCTCATGAATTTTGCTCTCAACATACAATGCTAGTTAAACAGGGTGATGATTATGTGTACCTTCCTTACCCAGATCCATCAAGAATCCTAGGGGCCGGCTGTTTTGTAGATGATATCGTAAAAACAGATGGTACACTTATGATTGAACGGTTCGTGTCTTTAGCTATAGATGCTTACCCACTTACTAAACATCCTAATCAGGAGTATGCTGATGTCTTTCATTTGTACTTACAATACATAAGAAAGCTACATGATGAGTTAACAGGACACATGTTAGACATGTATTCTGTTATGCTTACTAATGATAACACTTCAAGGTATTGGGAACCTGAGTTTTATGAGGCTATGTACACACCGCATACAGTCTTACAGGCTGTTGGGGCTTGTGTTCTTTGCAATTCACAGACTTCATTAAGATGTGGTGCTTGCATACGTAGACCATTCTTATGTTGTAAATGCTGTTACGACCATGTCATATCAACATCACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATGCTCCAGGTTGTGATGTCACAGATGTGACTCAACTTTACTTAGGAGGTATGAGCTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTGCTAATGGACAAGTTTTTGGTTTATATAAAAATACATGTGTTGGTAGCGATAATGTTACTGACTTTAATGCAATTGCAACATGTGACTGGACAAATGCTGGTGATTACATTTTAGCTAACACCTGTACTGAAAGACTCAAGCTTTTTGCAGCAGAAACGCTCAAAGCTACTGAGGAGACATTTAAACTGTCTTATGGTATTGCTACTGTACGTGAAGTGCTGTCTGACAGAGAATTACATCTTTCATGGGAAGTTGGTAAACCTAGACCACCACTTAACCGAAATTATGTCTTTACTGGTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGGAGAGTACACCTTTGAAAAAGGTGACTATGGTGATGCTGTTGTTTACCGAGGTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTGCTGACATCACATACAGTAATGCCATTAAGTGCACCTACACTAGTGCCACAAGAGCACTATGTTAGAATTACTGGCTTATACCCAACACTCAATATCTCAGATGAGTTTTCTAGCAATGTTGCAAATTATCAAAAGGTTGGTATGCAAAAGTATTCTACACTCCAGGGACCACCTGGTACTGGTAAGAGTCATTTTGCTATTGGCCTAGCTCTCTACTACCCTTCTGCTCGCATAGTGTATACAGCTTGCTCTCATGCCGCTGTTGATGCACTATGTGAGAAGGCATTAAAATATTTGCCTATAGATAAATGTAGTAGAATTATACCTGCACGTGCTCGTGTAGAGTGTTTTGATAAATTCAAAGTGAATTCAACATTAGAACAGTATGTCTTTTGTACTGTAAATGCATTGCCTGAGACGACAGCAGATATAGTTGTCTTTGATGAAATTTCAATGGCCACAAATTATGATTTGAGTGTTGTCAATGCCAGATTACGTGCTAAGCACTATGTGTACATTGGCGACCCTGCTCAATTACCTGCACCACGCACATTGCTAACTAAGGGCACACTAGAACCAGAATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAGGTCCAGACATGTTCCTCGGAACTTGTCGGCGTTGTCCTGCTGAAATTGTTGACACTGTGAGTGCTTTGGTTTATGATAATAAGCTTAAAGCACATAAAGACAAATCAGCTCAATGCTTTAAAATGTTTTATAAGGGTGTTATCACGCATGATGTTTCATCTGCAATTAACAGGCCACAAATAGGCGTGGTAAGAGAATTCCTTACACGTAACCCTGCTTGGAGAAAAGCTGTCTTTATTTCACCTTATAATTCACAGAATGCTGTAGCCTCAAAGATTTTGGGACTACCAACTCAAACTGTTGATTCATCACAGGGCTCAGAATATGACTATGTCATATTCACTCAAACCACTGAAACAGCTCACTCTTGTAATGTAAACAGATTTAATGTTGCTATTACCAGAGCAAAAGTAGGCATACTTTGCATAATGTCTGATAGAGACCTTTATGACAAGTTGCAATTTACAAGTCTTGAAATTCCACGTAGGAATGTGGCAACTTTACAAGCTGAAAATGTAACAGGACTCTTTAAAGATTGTAGTAAGGTAATCACTGGGTTACATCCTACACAGGCACCTACACACCTCAGTGTTGACACTAAATTCAAAACTGAAGGTTTATGTGTTGACATACCTGGCATACCTAAGGACATGACCTATAGAAGACTCATCTCTATGATGGGTTTTAAAATGAATTATCAAGTTAATGGTTACCCTAACATGTTTATCACCCGCGAAGAAGCTATAAGACATGTACGTGCATGGATTGGCTTCGATGTCGAGGGGTGTCATGCTACTAGAGAAGCTGTTGGTACCAATTTACCTTTACAGCTAGGTTTTTCTACAGGTGTTAACCTAGTTGCTGTACCTACAGGTTATGTTGATACACCTAATAATACAGATTTTTCCAGAGTTAGTGCTAAACCACCGCCTGGAGATCAATTTAAACACCTCATACCACTTATGTACAAAGGACTTCCTTGGAATGTAGTGCGTATAAAGATTGTACAAATGTTAAGTGACACACTTAAAAATCTCTCTGACAGAGTCGTATTTGTCTTATGGGCACATGGCTTTGAGTTGACATCTATGAAGTATTTTGTGAAAATAGGACCTGAGCGCACCTGTTGTCTATGTGATAGACGTGCCACATGCTTTTCCACTGCTTCAGACACTTATGCCTGTTGGCATCATTCTATTGGATTTGATTACGTCTATAATCCGTTTATGATTGATGTTCAACAATGGGGTTTTACAGGTAACCTACAAAGCAACCATGATCTGTATTGTCAAGTCCATGGTAATGCACATGTAGCTAGTTGTGATGCAATCATGACTAGGTGTCTAGCTGTCCACGAGTGCTTTGTTAAGCGTGTTGACTGGACTATTGAATATCCTATAATTGGTGATGAACTGAAGATTAATGCGGCTTGTAGAAAGGTTCAACACATGGTTGTTAAAGCTGCATTATTAGCAGACAAATTCCCAGTTCTTCACGACATTGGTAACCCTAAAGCTATTAAGTGTGTACCTCAAGCTGATGTAGAATGGAAGTTCTATGATGCACAGCCTTGTAGTGACAAAGCTTATAAAATAGAAGAATTATTCTATTCTTATGCCACACATTCTGACAAATTCACAGATGGTGTATGCCTATTTTGGAATTGCAATGTCGATAGATATCCTGCTAATTCCATTGTTTGTAGATTTGACACTAGAGTGCTATCTAACCTTAACTTGCCTNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNACAAACAATTTGATACTTATAACCTCTGGAACACTTTTACAAGACTTCAGAGTTTAGAAAATGTGGCTTTTAATGTTGTAAATAAGGGACACTTTGATGGACAACAGGGTGAAGTACCAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATGGTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTGAGCTTTGGGCTAAGCGCAACATTAAACCAGTACCAGAGGTGAAAATACTCAATAATTTGGGTGTGGACATTGCTGCTAATACTGTGATCTGGGACTACAAAAGAGATGCTCCAGCACATATATCTACTATTGGTGTTTGTTCTATGACTGACATAGCCAAGAAACCAACTGAAACGATTTGTGCACCACTCACTGTCTTTTTTGATGGTAGAGTTGATGGTCAAGTAGACTTATTTAGAAATGCCCGTAATGGTGTTCTTATTACAGAAGGTAGTGTTAAAGGTTTACAACCATCTGTAGGTCCCAAACAAGCTAGTCTTAATGGAGTCACATTAATTGGAGAAGCCGTAAAAACACAGTTCAATTATTATAAGAAAGTTGATGGTGTTGTCCAACAATTACCTGAAACTTACTTTACTCAGAGTAGAAATTTACAAGAATTTAAACCCAGGAGTCAAATGGAAATTGATTTCTTAGAATTAGCTATGGATGAATTCATTGAACGGTATAAATTAGAAGGCTATGCCTTCGAACATATCGTTTATGGAGATTTTAGTCATAGTCAGTTAGGTGGTTTACATCTACTGATTGGACTAGCTAAACGTTTTAAGGAATCACCTTTTGAATTAGAAGATTTTATTCCTATGGACAGTACAGTTAAAAACTATTTCATAACAGATGCGCAAACAGGTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTACTTGATGATTTTGTTGAAATAATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTGACTATACAGAAATTTCATTTATGCTTTGGTGTAAAGATGGCCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTGGCAACCGGGTGTTGCTATGCCTAATCTTTACAAAATGCAAAGAATGCTATTAGAAAAGTGTGACCTTCAAAATTATGGTGATAGTGCAACATTACCTAAAGGCATAATGATGAATGTCGCAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAGCTGTACCCTATAATATGAGAGTTATACATTTTGGTGCTGGTTCTGATAAAGGAGTTGCACCAGGTACAGCTGTTTTAAGACAGTGGTTGCCTACGGGTACGCTGCTTGTCGATTCAGATCTTAATGACTTTGTCTCTGATGCAGATTCAACTTTGATTGGTGATTGTGCAACTGTACATACAGCTAATAAATGGGATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAATGTTACAAAAGAAAATGACTCTAAAGAGGGTTTTTTCACTTACATTTGTGGGTTTATACAACAAAAGCTAGCTCTTGGAGGTTCCGTGGCTATAAAGATAACAGAACATTCTTGGAATGCTGATCTTTATAAGCTCATGGGACACTTCGCATGGTGGACAGCCTTTGTTACTAATGTGAATGCGTCATCATCTGAAGCATTTTTAATTGGATGTAATTATCTTGGCAAACCACGCGAACAAATAGATGGTTATGTCATGCATGCAAATTACATATTTTGGAGGAATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTGACATGAGTAAATTTCCCCTTAAATTAAGGGGTACTGCTGTTATGTCTTTAAAAGAAGGTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAGGTAGACTTATAATTAGAGAAAACAACAGAGTTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAAACGAACTTATGGATTTGTTTATGAGAATCTTCACAATTGGAACTGTAATTTTGAAGCAAGGTGAAATCAAGGATGCTACTCCTTCAGATTTTGTTCGCGCTACTGCAACGATACCGATACAAGCCTCACTCCCTTTCGGATGGCTTATTGTTGGCGTTGCACTTCTTGCTGTTTTTCAGAGCGCTTCCAAAATCATAACCCTCAAAAAGAGATGGCAACTAGCACTCTCCAAGGGTGTTCACTTTGTTTGCAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTGCTCGTTGCTGCTGGCCTTGAAGCCCCTTTTCTCTATCTTTATGCTTTAGTCTACTTCTTGCAGAGTATAAACTTTGTAAGAATAATAATGAGGCTTTGGCTTTGCTGGAAATGCCGTTCCAAAAACCCATTACTTTATGATGCCAACTATTTTCTTTGCTGGCATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTCAGGTGATGGCACAACAAGTCCTATTTCTGAACATGACTACCAGATTGGTGGTTATACTGAAAAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAGCTGTACTCAACTCAATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTGATGAGCCTGAAGAACATGTCCAAATTCACACAATCGACGGTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATGATGAACCGACGACGACTACTAGCGTGCCTTTGTAAGCACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGGAAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTACCGTTGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAATTTGCCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGGAGCTGTGATCCTTCGTGGACATCTTCGTATTGCTGGACACCATCTAGGACGCTGTGACATCAAGGACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGGGAGCTTCGCAGCGTGTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAGATATTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATGGAGATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCACTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAACACNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNATTCCTTGTTTTAATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTCTAAATGGTATATTAGAGTAGGAGCTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAGATCTCAGTCCAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATGGGTTGCAACTGAGGGAGCCTTGAATACACCAAAAGATCACATTGGCACCCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAAGGGAGCAGAGGCGGCAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCGCAACAGTTCAAGAAATTCAACTCCAGGCAGCAGTAGGGGAACTTCTCCTGCTAGAATGGCTGGCAATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAANNNNNNNCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAGGGAGGACTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCC From e1ecc637e073c0e64b6d8adfcf7178f376d0cd4b Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 13 Dec 2024 11:01:05 -0800 Subject: [PATCH 137/161] updated covidmvp workflow --- workflows/covidmvp.nf | 3 +-- 1 file changed, 1 insertion(+), 2 deletions(-) diff --git a/workflows/covidmvp.nf b/workflows/covidmvp.nf index 1e9a3cf1..95c8381d 100644 --- a/workflows/covidmvp.nf +++ b/workflows/covidmvp.nf @@ -103,7 +103,6 @@ workflow COVIDMVP { POSTPROCESSING(annotated_gvf, PREPROCESSING.out.logfile) } if (!params.skip_surveillance) { - ch_metadata = params.metadata ? Channel.value(file(params.metadata)) : Channel.value(null) - SURVEILLANCE(annotated_gvf, ch_metadata) + SURVEILLANCE(annotated_gvf, metadata) } } From 1f8f4e8e0f8886ba113ff8ad14f510beb8e693ca Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 13 Dec 2024 11:02:04 -0800 Subject: [PATCH 138/161] updated subworkflows --- subworkflows/local/input_check.nf | 23 ++++---- subworkflows/local/virusmvp_annotation.nf | 10 ++-- subworkflows/local/virusmvp_classification.nf | 2 +- subworkflows/local/virusmvp_config.nf | 7 +-- subworkflows/local/virusmvp_postprocessing.nf | 54 +++++++++---------- subworkflows/local/virusmvp_qc.nf | 2 +- subworkflows/local/virusmvp_surveillance.nf | 2 +- subworkflows/local/virusmvp_variantcalling.nf | 4 +- 8 files changed, 47 insertions(+), 57 deletions(-) diff --git a/subworkflows/local/input_check.nf b/subworkflows/local/input_check.nf index 0aecf87f..9d5e9e75 100644 --- a/subworkflows/local/input_check.nf +++ b/subworkflows/local/input_check.nf @@ -9,36 +9,33 @@ workflow INPUT_CHECK { samplesheet // file: /path/to/samplesheet.csv main: - SAMPLESHEET_CHECK ( samplesheet ) - .csv - .splitCsv ( header:true, sep:',' ) - .map { create_fastq_channel(it) } - .set { reads } + SAMPLESHEET_CHECK(samplesheet).csv.splitCsv(header: true, sep: ',').map { create_fastq_channel(it) }.set { reads } emit: - reads // channel: [ val(meta), [ reads ] ] + reads // channel: [ val(meta), [ reads ] ] versions = SAMPLESHEET_CHECK.out.versions // channel: [ versions.yml ] } // Function to get list of [ meta, [ fastq_1, fastq_2 ] ] -def create_fastq_channel(LinkedHashMap row) { +def create_fastq_channel(row) { // create meta map def meta = [:] - meta.id = row.sample + meta.id = row.sample meta.single_end = row.single_end.toBoolean() // add path(s) of the fastq file(s) to the meta map def fastq_meta = [] if (!file(row.fastq_1).exists()) { - exit 1, "ERROR: Please check input samplesheet -> Read 1 FastQ file does not exist!\n${row.fastq_1}" + exit(1, "ERROR: Please check input samplesheet -> Read 1 FastQ file does not exist!\n${row.fastq_1}") } if (meta.single_end) { - fastq_meta = [ meta, [ file(row.fastq_1) ] ] - } else { + fastq_meta = [meta, [file(row.fastq_1)]] + } + else { if (!file(row.fastq_2).exists()) { - exit 1, "ERROR: Please check input samplesheet -> Read 2 FastQ file does not exist!\n${row.fastq_2}" + exit(1, "ERROR: Please check input samplesheet -> Read 2 FastQ file does not exist!\n${row.fastq_2}") } - fastq_meta = [ meta, [ file(row.fastq_1), file(row.fastq_2) ] ] + fastq_meta = [meta, [file(row.fastq_1), file(row.fastq_2)]] } return fastq_meta } diff --git a/subworkflows/local/virusmvp_annotation.nf b/subworkflows/local/virusmvp_annotation.nf index c5d941c5..295a01ee 100644 --- a/subworkflows/local/virusmvp_annotation.nf +++ b/subworkflows/local/virusmvp_annotation.nf @@ -12,12 +12,12 @@ include { ANNOTATEMATPEPTIDES_NCOV } from '../../modules/local/annotatematpeptid workflow ANNOTATION { take: - annotation_vcf - ch_snpeff_db + annotation_vcf + ch_snpeff_db ch_snpeff_config - viral_genome - ch_stats - ch_json + viral_genome + ch_stats + ch_json main: lineage = true diff --git a/subworkflows/local/virusmvp_classification.nf b/subworkflows/local/virusmvp_classification.nf index d64f8b8f..65c71271 100644 --- a/subworkflows/local/virusmvp_classification.nf +++ b/subworkflows/local/virusmvp_classification.nf @@ -15,7 +15,7 @@ include { NEXTCLADE_DATASETGET } from '../../modules/nf-core/nextclade // Define the workflow workflow CLASSIFICATION { take: - metadata + metadata sequences main: diff --git a/subworkflows/local/virusmvp_config.nf b/subworkflows/local/virusmvp_config.nf index 9de8aec5..fc0638ea 100644 --- a/subworkflows/local/virusmvp_config.nf +++ b/subworkflows/local/virusmvp_config.nf @@ -8,7 +8,6 @@ include { SNPEFF_BUILD } from '../../modules/local/snpeff_build' include { SAMTOOLS_FAIDX } from '../../modules/nf-core/samtools/faidx/main' workflow CONFIGURE_VIRUSMVP { - main: ch_snpeff_db = Channel.empty() ch_snpeff_config = Channel.empty() @@ -22,11 +21,7 @@ workflow CONFIGURE_VIRUSMVP { ch_snpeff_db = SNPEFF_BUILD.out.db ch_snpeff_config = SNPEFF_BUILD.out.config - //SAMTOOLS_FAIDX([[id: params.virus_accession_id], params.viral_genome], [[], []]) - //ch_viral_fai = SAMTOOLS_FAIDX.out.fai - emit: - ch_snpeff_db + ch_snpeff_db ch_snpeff_config - //ch_viral_fai } diff --git a/subworkflows/local/virusmvp_postprocessing.nf b/subworkflows/local/virusmvp_postprocessing.nf index 5e7fa4a1..ff73b670 100644 --- a/subworkflows/local/virusmvp_postprocessing.nf +++ b/subworkflows/local/virusmvp_postprocessing.nf @@ -3,39 +3,37 @@ nextflow.enable.dsl = 2 // import modules -include { GVF_TO_INDEX_LOG } from '../../modules/local/gvftoindexandlog' -include { MERGE_INDICES } from '../../modules/local/mergeIndices' -include { MERGE_LOGFILES } from '../../modules/local/mergeLogfiles' +include { GVF_TO_INDEX_LOG } from '../../modules/local/gvftoindexandlog' +include { MERGE_INDICES } from '../../modules/local/mergeIndices' +include { MERGE_LOGFILES } from '../../modules/local/mergeLogfiles' workflow POSTPROCESSING { take: - gvf - logheader + gvf + logheader main: - GVF_TO_INDEX_LOG(gvf) - ch_indexfile=Channel.empty() - if (!params.mutation_indexfile) { - ch_indexfile = [[],[]] - } - else { - ch_indexfile = [[id:params.virus_accession_id], file(params.mutation_indexfile, checkIfExists: true)] - } - GVF_TO_INDEX_LOG.out.index - .map { [it[1]] } - .collect() - .map { indices -> [ [id:"mergingindices"], indices ] } - .set { ch_indices} - MERGE_INDICES(ch_indices, ch_indexfile) - - GVF_TO_INDEX_LOG.out.log - .map { [it[1]] } - .collect() - .map { logs -> [ [id:"merginglogfiles"], logs ] } - .set { ch_logs} + GVF_TO_INDEX_LOG(gvf) + ch_indexfile = Channel.empty() + if (!params.mutation_indexfile) { + ch_indexfile = [[], []] + } + else { + ch_indexfile = [[id: params.virus_accession_id], file(params.mutation_indexfile, checkIfExists: true)] + } + GVF_TO_INDEX_LOG.out.index + .map { [it[1]] } + .collect() + .map { indices -> [[id: "mergingindices"], indices] } + .set { ch_indices } + MERGE_INDICES(ch_indices, ch_indexfile) - MERGE_LOGFILES(logheader, ch_logs, ch_indexfile) - - + GVF_TO_INDEX_LOG.out.log + .map { [it[1]] } + .collect() + .map { logs -> [[id: "merginglogfiles"], logs] } + .set { ch_logs } + + MERGE_LOGFILES(logheader, ch_logs, ch_indexfile) } diff --git a/subworkflows/local/virusmvp_qc.nf b/subworkflows/local/virusmvp_qc.nf index add49606..ddd39675 100644 --- a/subworkflows/local/virusmvp_qc.nf +++ b/subworkflows/local/virusmvp_qc.nf @@ -8,7 +8,7 @@ include { SEQKIT_STATS } from '../../modules/nf-core/seqkit/stats/main' workflow QUALITYCONTROL { take: - sequences + sequences ch_collected_sequences main: diff --git a/subworkflows/local/virusmvp_surveillance.nf b/subworkflows/local/virusmvp_surveillance.nf index 70d17683..b97fdf58 100644 --- a/subworkflows/local/virusmvp_surveillance.nf +++ b/subworkflows/local/virusmvp_surveillance.nf @@ -14,12 +14,12 @@ workflow SURVEILLANCE { GVF2TSV(ch_gvf) tsv = GVF2TSV.out.surveillancetsv surveillance_indicators = Channel.value([id: "surveillance", file: params.surveillance_indicators]) + if (params.mode == 'reference') { metadata = ch_metadata } else { metadata = [[], []] } - // Use a conditional operator to handle the case where metadata might be null TSV2PDF(tsv, surveillance_indicators, metadata) } diff --git a/subworkflows/local/virusmvp_variantcalling.nf b/subworkflows/local/virusmvp_variantcalling.nf index 0b45954f..735ea7c3 100644 --- a/subworkflows/local/virusmvp_variantcalling.nf +++ b/subworkflows/local/virusmvp_variantcalling.nf @@ -20,8 +20,8 @@ include { BAM_SORT_STATS_SAMTOOLS } from '../nf-core/bam_sor workflow VARIANT_CALLING { take: sequences_grouped - viral_genome - viral_genome_fai + viral_genome + viral_genome_fai main: From 15b17c980313f8a65c0705d79b09a808bf88314c Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 13 Dec 2024 11:02:31 -0800 Subject: [PATCH 139/161] updated and formatted modules --- modules/local/addVariantAnnotation.nf | 31 ++++++++-------- modules/local/annotatematpeptides_ncov.nf | 28 +++++++-------- modules/local/arcticdownloadscheme.nf | 10 +++--- modules/local/downloadPangoalias.nf | 9 +++-- modules/local/extractVariants.nf | 1 - modules/local/harmonize_metadata.nf | 28 +++++++-------- modules/local/help.nf | 14 ++++---- modules/local/ivar.nf | 9 +++-- modules/local/mergeLogfiles.nf | 29 +++++++-------- modules/local/postprocessing.nf | 8 ++--- modules/local/samplesheet_check.nf | 15 ++++---- modules/local/snpeff_ann.nf | 30 ++++++++-------- modules/local/snpeff_build.nf | 21 +++++------ modules/local/splitmutations_gvf.nf | 24 ++++++------- modules/local/splitmutations_pokay.nf | 24 ++++++------- modules/local/tagproblematicsites_ncov.nf | 40 ++++++++++----------- modules/local/viralai/viralai_metadata.nf | 14 ++++---- modules/local/viralai/viralai_multifasta.nf | 2 +- modules/local/wf_header.nf | 2 +- 19 files changed, 170 insertions(+), 169 deletions(-) diff --git a/modules/local/addVariantAnnotation.nf b/modules/local/addVariantAnnotation.nf index 80ae8917..a715a7c1 100644 --- a/modules/local/addVariantAnnotation.nf +++ b/modules/local/addVariantAnnotation.nf @@ -1,19 +1,19 @@ process VARIANTANNOTATION { - tag "$meta.id" + tag "${meta.id}" conda "conda-forge::pandas=1.4.3" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/pandas:1.4.3': - 'amancevice/pandas:1.4.3' }" - + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' + : 'amancevice/pandas:1.4.3'}" + input: - tuple val(meta), path(gvf) - tuple val(meta2), path(tsv) - val lineage - + tuple val(meta), path(gvf) + tuple val(meta2), path(tsv) + val lineage + output: - tuple val(meta), path("*.gvf"), emit: gvf + tuple val(meta), path("*.gvf"), emit: gvf script: @@ -23,11 +23,10 @@ process VARIANTANNOTATION { """ addvariantinfo2gvf.py \\ - --ingvf $gvf \\ - $strain \\ - $args \\ + --ingvf ${gvf} \\ + ${strain} \\ + ${args} \\ --outgvf ${prefix}_annotated.gvf \\ - --clades $tsv + --clades ${tsv} """ - -} \ No newline at end of file +} diff --git a/modules/local/annotatematpeptides_ncov.nf b/modules/local/annotatematpeptides_ncov.nf index 80da94f6..7d05a5a7 100644 --- a/modules/local/annotatematpeptides_ncov.nf +++ b/modules/local/annotatematpeptides_ncov.nf @@ -1,32 +1,32 @@ process ANNOTATEMATPEPTIDES_NCOV { - tag "$meta.id" + tag "${meta.id}" conda "bioconda::cyvcf=0.8.0 bioconda::gffutils=0.10.1" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'cidgoh/nf-ncov-voc-extra:0.2': - 'cidgoh/nf-ncov-voc-extra:0.2'}" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'cidgoh/nf-ncov-voc-extra:0.2' + : 'cidgoh/nf-ncov-voc-extra:0.2'}" input: - tuple val(meta), path(vcf) - tuple val(meta2), path(json) + tuple val(meta), path(vcf) + tuple val(meta2), path(json) output: - tuple val(meta), path("*annotated.vcf"), emit: vcf - + tuple val(meta), path("*annotated.vcf"), emit: vcf + when: - vcf.size() > 0 + vcf.size() > 0 script: def args = task.ext.args ?: '' def prefix = task.ext.prefix ?: "${meta.id}" - """ + """ mature_peptide_annotation.py \\ - --vcf_file $vcf \\ - --json $json \\ + --vcf_file ${vcf} \\ + --json ${json} \\ --output_vcf ${prefix}.annotated.vcf \\ - $args + ${args} """ -} \ No newline at end of file +} diff --git a/modules/local/arcticdownloadscheme.nf b/modules/local/arcticdownloadscheme.nf index 8f23dca3..b39d3deb 100644 --- a/modules/local/arcticdownloadscheme.nf +++ b/modules/local/arcticdownloadscheme.nf @@ -1,15 +1,15 @@ -process articDownloadScheme{ +process articDownloadScheme { tag params.schemeRepoURL label 'internet' output: - path "${params.schemeDir}/${params.scheme}/${params.schemeVersion}/*.reference.fasta" , emit: reffasta - path "${params.schemeDir}/${params.scheme}/${params.schemeVersion}/*.primer.bed" , emit: bed - path "${params.schemeDir}" , emit: scheme + path "${params.schemeDir}/${params.scheme}/${params.schemeVersion}/*.reference.fasta", emit: reffasta + path "${params.schemeDir}/${params.scheme}/${params.schemeVersion}/*.primer.bed", emit: bed + path "${params.schemeDir}", emit: scheme script: """ git clone ${params.schemeRepoURL} ${params.schemeDir} """ -} \ No newline at end of file +} diff --git a/modules/local/downloadPangoalias.nf b/modules/local/downloadPangoalias.nf index 29c06f8f..8a9ba23a 100644 --- a/modules/local/downloadPangoalias.nf +++ b/modules/local/downloadPangoalias.nf @@ -1,10 +1,9 @@ -process DOWNLOADPANGOALIAS{ - +process DOWNLOADPANGOALIAS { output: - path("*.json"), emit: json - + path ("*.json"), emit: json + script: """ curl -L -o alias_key.json https://raw.githubusercontent.com/cov-lineages/pango-designation/master/pango_designation/alias_key.json """ -} \ No newline at end of file +} diff --git a/modules/local/extractVariants.nf b/modules/local/extractVariants.nf index 98fa35cf..238c302d 100644 --- a/modules/local/extractVariants.nf +++ b/modules/local/extractVariants.nf @@ -19,7 +19,6 @@ process EXTRACTVARIANTS { tuple val(meta), path("*.log"), emit: log, optional: true script: - def prefix = task.ext.prefix ?: "${meta.id}" def val_variant_file = variant_file ? "--variants ${variants}" : '' def virusseq_update = virusseq ? "--virusseq" : '' diff --git a/modules/local/harmonize_metadata.nf b/modules/local/harmonize_metadata.nf index 6ee44f40..7612a185 100644 --- a/modules/local/harmonize_metadata.nf +++ b/modules/local/harmonize_metadata.nf @@ -1,27 +1,27 @@ process METADATA_HARMONIZER { - tag "$meta.id" + tag "${meta.id}" conda "conda-forge::pandas=1.4.3" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'docker://pandas/pandas:pip-all': - 'pandas/pandas:pip-all' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'docker://pandas/pandas:pip-all' + : 'pandas/pandas:pip-all'}" input: - tuple val(meta), path(metadata) - path(yaml) - val(dataset) - + tuple val(meta), path(metadata) + path yaml + val dataset + output: - tuple val(meta), path("*.csv.gz"), emit: gz + tuple val(meta), path("*.csv.gz"), emit: gz script: - """ + """ harmonize_metadata.py \\ - --metadata $metadata \\ - --config $yaml \\ - --data $dataset \\ + --metadata ${metadata} \\ + --config ${yaml} \\ + --data ${dataset} \\ --outfile harmonized_metadata.csv.gz """ -} +} diff --git a/modules/local/help.nf b/modules/local/help.nf index 3db43891..7e35a647 100644 --- a/modules/local/help.nf +++ b/modules/local/help.nf @@ -1,5 +1,6 @@ def printHelp() { - log.info""" + log.info( + """ Usage: nextflow run main.nf -profile [singularity | docker | conda) --prefix [prefix] --mode [reference | user] [workflow-options] @@ -29,15 +30,15 @@ def printHelp() { --gisaid_metadata If lineage assignment is preferred by mapping metadata to GISAID metadata file, provide the metadata file (.tsv file) --variants Provide a variants file - (.tsv) (Default: $baseDir/assets/ncov_variants/variants_who.tsv) + (.tsv) (Default: ${baseDir}/assets/ncov_variants/variants_who.tsv) --outdir Output directory - (Default: $baseDir/results) + (Default: ${baseDir}/results) --gff Path to annotation gff for variant consequence calling and typing. - (Default: $baseDir/assets/ncov_genomeFeatures/MN908947.3.gff3) + (Default: ${baseDir}/assets/ncov_genomeFeatures/MN908947.3.gff3) --ref Path to SARS-CoV-2 reference fasta file - (Default: $baseDir/assets/ncov_refdb/*) + (Default: ${baseDir}/assets/ncov_refdb/*) --bwa_index Path to BWA index files - (Default: $baseDir/assets/ncov_refdb/*) + (Default: ${baseDir}/assets/ncov_refdb/*) Selection options: @@ -84,4 +85,5 @@ def printHelp() { statement to the surveillance report. see https://virusseq-dataportal.ca/acknowledgements """.stripIndent() + ) } diff --git a/modules/local/ivar.nf b/modules/local/ivar.nf index 6c9edbb2..c0459d68 100644 --- a/modules/local/ivar.nf +++ b/modules/local/ivar.nf @@ -1,19 +1,18 @@ process IVAR { tag { "${bam.baseName}" } - publishDir "${params.outdir}/${params.prefix}/${task.process.replaceAll(":","_")}", pattern: "*.variants.tsv", mode: 'copy' + publishDir "${params.outdir}/${params.prefix}/${task.process.replaceAll(":", "_")}", pattern: "*.variants.tsv", mode: 'copy' label 'dev_env' input: - tuple(path(bam), path(ref), path(ref_gff)) + tuple path(bam), path(ref), path(ref_gff) output: - path("*.variants.tsv"), emit: variants - + path ("*.variants.tsv"), emit: variants script: - """ + """ samtools mpileup -aa -A -d ${params.var_MaxDepth} -s --output-MQ -O --reference ${ref} ${bam} |\ ivar variants \ -r ${ref} \ diff --git a/modules/local/mergeLogfiles.nf b/modules/local/mergeLogfiles.nf index 0b66edf1..0dd27e31 100644 --- a/modules/local/mergeLogfiles.nf +++ b/modules/local/mergeLogfiles.nf @@ -1,21 +1,22 @@ process MERGE_LOGFILES { -tag "${meta.id}" -conda "conda-forge::dask=2023.10.1" -container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container? -'biocontainers/dask:2023.10.1-py11-ol9_cv1': 'quay.io/biocontainers/dask:2023.10.1-py11-ol9_cv1'}" + tag "${meta.id}" + conda "conda-forge::dask=2023.10.1" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'biocontainers/dask:2023.10.1-py11-ol9_cv1' + : 'quay.io/biocontainers/dask:2023.10.1-py11-ol9_cv1'}" -input: -tuple val(meta), path(log_header) -tuple val(meta2), path(logs) -tuple val(meta3), path(index) + input: + tuple val(meta), path(log_header) + tuple val(meta2), path(logs) + tuple val(meta3), path(index) -output: -tuple val(meta), path("*.tsv"), emit: merged_logfile + output: + tuple val(meta), path("*.tsv"), emit: merged_logfile -script: -def end_date = "${params.end_date}" -def last_index = index ? "--original_index ${index}" : '' -""" + script: + def end_date = "${params.end_date}" + def last_index = index ? "--original_index ${index}" : '' + """ merge_logfiles.py \\ --log_header ${log_header} \\ --gvf_log ${logs} \\ diff --git a/modules/local/postprocessing.nf b/modules/local/postprocessing.nf index bcad3079..ae105788 100644 --- a/modules/local/postprocessing.nf +++ b/modules/local/postprocessing.nf @@ -1,12 +1,12 @@ process POSTPROCESSING { - tag {"linking output files to rsync"} + tag { "linking output files to rsync" } input: - val surveillance + val surveillance script: - """ + """ rm -rf /scratch/mzanwar/COVID-MVP/nf-ncov-voc/latest_gvf/* ln -s ${params.outdir}/${params.prefix}/annotation_vcfTogvf/* /scratch/mzanwar/COVID-MVP/nf-ncov-voc/latest_gvf/ @@ -16,4 +16,4 @@ process POSTPROCESSING { rm -rf /scratch/mzanwar/COVID-MVP/nf-ncov-voc/latest_pdf/* ln -s ${params.outdir}/${params.prefix}/surveillance_surveillancePDF/* /scratch/mzanwar/COVID-MVP/nf-ncov-voc/latest_pdf/ """ -} \ No newline at end of file +} diff --git a/modules/local/samplesheet_check.nf b/modules/local/samplesheet_check.nf index 98504410..63cdaad7 100644 --- a/modules/local/samplesheet_check.nf +++ b/modules/local/samplesheet_check.nf @@ -1,26 +1,27 @@ process SAMPLESHEET_CHECK { - tag "$samplesheet" + tag "${samplesheet}" label 'process_single' conda "conda-forge::python=3.8.3" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/python:3.8.3' : - 'quay.io/biocontainers/python:3.8.3' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/python:3.8.3' + : 'quay.io/biocontainers/python:3.8.3'}" input: path samplesheet output: - path '*.csv' , emit: csv + path '*.csv', emit: csv path "versions.yml", emit: versions when: task.ext.when == null || task.ext.when - script: // This script is bundled with the pipeline, in nf-core/seqqc/bin/ + script: + // This script is bundled with the pipeline, in nf-core/seqqc/bin/ """ check_samplesheet.py \\ - $samplesheet \\ + ${samplesheet} \\ samplesheet.valid.csv cat <<-END_VERSIONS > versions.yml diff --git a/modules/local/snpeff_ann.nf b/modules/local/snpeff_ann.nf index 17517535..a6a7452e 100644 --- a/modules/local/snpeff_ann.nf +++ b/modules/local/snpeff_ann.nf @@ -1,24 +1,24 @@ process SNPEFF_ANN { - tag "$meta.id" + tag "${meta.id}" label 'process_medium' conda "bioconda::snpeff=5.1" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/snpeff:5.1--hdfd78af_2' : - 'quay.io/biocontainers/snpeff:5.1--hdfd78af_2' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/snpeff:5.1--hdfd78af_2' + : 'quay.io/biocontainers/snpeff:5.1--hdfd78af_2'}" input: tuple val(meta), path(vcf) - path db - path config - path fasta + path db + path config + path fasta output: - tuple val(meta), path("*.vcf") , emit: vcf - tuple val(meta), path("*.csv") , emit: csv + tuple val(meta), path("*.vcf"), emit: vcf + tuple val(meta), path("*.csv"), emit: csv tuple val(meta), path("*.genes.txt"), emit: txt - tuple val(meta), path("*.html") , emit: html - path "versions.yml" , emit: versions + tuple val(meta), path("*.html"), emit: html + path "versions.yml", emit: versions when: task.ext.when == null || task.ext.when @@ -35,10 +35,10 @@ process SNPEFF_ANN { snpEff \\ -Xmx${avail_mem}g \\ ${fasta.baseName} \\ - -config $config \\ - -dataDir $db \\ - $args \\ - $vcf \\ + -config ${config} \\ + -dataDir ${db} \\ + ${args} \\ + ${vcf} \\ -csvStats ${prefix}.snpeff.csv \\ > ${prefix}.snpeff.vcf mv snpEff_summary.html ${prefix}.snpeff.summary.html diff --git a/modules/local/snpeff_build.nf b/modules/local/snpeff_build.nf index 491108d2..feca37c1 100644 --- a/modules/local/snpeff_build.nf +++ b/modules/local/snpeff_build.nf @@ -1,19 +1,19 @@ process SNPEFF_BUILD { - tag "$fasta" + tag "${fasta}" label 'process_low' conda "bioconda::snpeff=5.1" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/snpeff:5.1d--hdfd78af_0' : - 'quay.io/biocontainers/snpeff:5.1d--hdfd78af_0' }" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/snpeff:5.1d--hdfd78af_0' + : 'quay.io/biocontainers/snpeff:5.1d--hdfd78af_0'}" input: path fasta path gbk output: - path 'snpeff_db' , emit: db - path '*.config' , emit: config + path 'snpeff_db', emit: db + path '*.config', emit: config path "versions.yml", emit: versions when: @@ -24,18 +24,19 @@ process SNPEFF_BUILD { def avail_mem = 6 if (!task.memory) { - log.info '[snpEff] Available memory not known - defaulting to 6GB. Specify process memory requirements to change this.' - } else { + log.info('[snpEff] Available memory not known - defaulting to 6GB. Specify process memory requirements to change this.') + } + else { avail_mem = task.memory.giga } """ mkdir -p snpeff_db/genomes/ cd snpeff_db/genomes/ - ln -s ../../$fasta ${basename}.fa + ln -s ../../${fasta} ${basename}.fa cd ../../ mkdir -p snpeff_db/${basename}/ cd snpeff_db/${basename}/ - ln -s ../../$gbk genes.gbk + ln -s ../../${gbk} genes.gbk cd ../../ echo "${basename}.genome : ${basename}" > snpeff.config snpEff \\ diff --git a/modules/local/splitmutations_gvf.nf b/modules/local/splitmutations_gvf.nf index b0081f78..3d6c6c23 100644 --- a/modules/local/splitmutations_gvf.nf +++ b/modules/local/splitmutations_gvf.nf @@ -1,18 +1,18 @@ process NCOVSPLITMUTATIONSGVF { - tag "$meta.id" + tag "${meta.id}" conda "conda-forge::pandas=1.4.3" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/pandas:1.4.3': - 'amancevice/pandas:1.4.3' }" - + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' + : 'amancevice/pandas:1.4.3'}" + input: - tuple val(meta), path(gvf) - path(tsv) + tuple val(meta), path(gvf) + path tsv output: - tuple val(meta), path("*.gvf"), emit: gvf + tuple val(meta), path("*.gvf"), emit: gvf script: @@ -20,10 +20,10 @@ process NCOVSPLITMUTATIONSGVF { def prefix = task.ext.prefix ?: "${meta.id}" """ - splitmutationnames_gvf.py --ingvf $gvf \\ - --names_to_split $tsv \\ - $args \\ + splitmutationnames_gvf.py --ingvf ${gvf} \\ + --names_to_split ${tsv} \\ + ${args} \\ --outgvf ${prefix}.processed.gvf """ -} \ No newline at end of file +} diff --git a/modules/local/splitmutations_pokay.nf b/modules/local/splitmutations_pokay.nf index 52599ebe..07f4cdda 100644 --- a/modules/local/splitmutations_pokay.nf +++ b/modules/local/splitmutations_pokay.nf @@ -1,18 +1,18 @@ process NCOVSPLITMUTATIONSPOKAY { - tag "$meta.id" + tag "${meta.id}" conda "conda-forge::pandas=1.4.3" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/pandas:1.4.3': - 'amancevice/pandas:1.4.3' }" - + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' + : 'amancevice/pandas:1.4.3'}" + input: - tuple val(meta), path(annotations) - path(tsv) + tuple val(meta), path(annotations) + path tsv output: - tuple val(meta), path("*.tsv"), emit: tsv + tuple val(meta), path("*.tsv"), emit: tsv script: @@ -20,10 +20,10 @@ process NCOVSPLITMUTATIONSPOKAY { def prefix = task.ext.prefix ?: "${meta.id}" """ - splitmutationnames_functionalannotation.py --functional_annotations $annotations \\ - --names_to_split $tsv \\ - $args \\ + splitmutationnames_functionalannotation.py --functional_annotations ${annotations} \\ + --names_to_split ${tsv} \\ + ${args} \\ --out_functions ${prefix}.processed.tsv """ -} \ No newline at end of file +} diff --git a/modules/local/tagproblematicsites_ncov.nf b/modules/local/tagproblematicsites_ncov.nf index da2c563d..15c8cdfa 100644 --- a/modules/local/tagproblematicsites_ncov.nf +++ b/modules/local/tagproblematicsites_ncov.nf @@ -1,31 +1,31 @@ process TAGPROBLEMATICSITES_NCOV { - tag "$meta.id" + tag "${meta.id}" - conda "bioconda::cyvcf=0.8.0 bioconda::gffutils=0.10.1" - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'https://depot.galaxyproject.org/singularity/cyvcf2:0.8.0--py36_0' : - 'cidgoh/nf-ncov-voc-extra:0.2' }" - - input: - tuple val(meta), path(vcf) - tuple val(meta2), path(prob_vcf) + conda "bioconda::cyvcf=0.8.0 bioconda::gffutils=0.10.1" + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'https://depot.galaxyproject.org/singularity/cyvcf2:0.8.0--py36_0' + : 'cidgoh/nf-ncov-voc-extra:0.2'}" - output: - tuple val(meta), path("*.vcf"), emit: vcf + input: + tuple val(meta), path(vcf) + tuple val(meta2), path(prob_vcf) - when: - vcf.size() > 0 + output: + tuple val(meta), path("*.vcf"), emit: vcf - script: - def args = task.ext.args ?: '' - def prefix = task.ext.prefix ?: "${meta.id}" + when: + vcf.size() > 0 - """ + script: + def args = task.ext.args ?: '' + def prefix = task.ext.prefix ?: "${meta.id}" + + """ problematic_sites_tag.py \\ - --vcffile $vcf \\ - --filter_vcf $prob_vcf \\ + --vcffile ${vcf} \\ + --filter_vcf ${prob_vcf} \\ --output_vcf ${prefix}.filtered.vcf \\ - $args + ${args} """ } diff --git a/modules/local/viralai/viralai_metadata.nf b/modules/local/viralai/viralai_metadata.nf index 76734257..d3f35830 100644 --- a/modules/local/viralai/viralai_metadata.nf +++ b/modules/local/viralai/viralai_metadata.nf @@ -1,19 +1,19 @@ process DOWNLOAD_VIRALAI_METADATA { - - container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? - 'docker://cidgoh/virus-mvp-viralai:latest': '' }" + + container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container + ? 'docker://cidgoh/virus-mvp-viralai:latest' + : 'cidgoh/virus-mvp-viralai:latest'}" output: - path("*.gz"), emit: csv + path ("*.gz"), emit: csv script: - def prefix = "virusseq-metadata" - + def prefix = "virusseq-metadata" + """ #!/usr/bin/env bash dnastack config set collections.url "${params.collections_api_url}" dnastack collections query ${params.collection_slug_name} "SELECT * FROM collections.${params.collection_slug_name}.samples ORDER BY sample_collection_date" --format csv | gzip > ${prefix}.csv.gz """ - } diff --git a/modules/local/viralai/viralai_multifasta.nf b/modules/local/viralai/viralai_multifasta.nf index 50b38f58..c619bab5 100644 --- a/modules/local/viralai/viralai_multifasta.nf +++ b/modules/local/viralai/viralai_multifasta.nf @@ -1,7 +1,7 @@ process DOWNLOAD_VIRALAI_MULTIFASTA { container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'docker://cidgoh/virus-mvp-viralai:latest' - : ''}" + : 'cidgoh/virus-mvp-viralai:latest'}" output: path ("*.xz"), emit: xz diff --git a/modules/local/wf_header.nf b/modules/local/wf_header.nf index 52bab3da..6812077b 100644 --- a/modules/local/wf_header.nf +++ b/modules/local/wf_header.nf @@ -1,4 +1,4 @@ -def workflowHeader(){ +def workflowHeader() { return """ ███╗ ██╗███████╗ ███╗ ██╗ ██████╗ ██████╗ ██╗ ██╗ ██╗ ██╗ ██████╗ ██████╗ From 4ccf0aa842059bad419b1bbf29c155236f9dadd7 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 13 Dec 2024 12:31:31 -0800 Subject: [PATCH 140/161] updated merge_indices --- bin/merge_indices.py | 8 +++++++- 1 file changed, 7 insertions(+), 1 deletion(-) diff --git a/bin/merge_indices.py b/bin/merge_indices.py index d8d30c0c..66fddd01 100755 --- a/bin/merge_indices.py +++ b/bin/merge_indices.py @@ -58,7 +58,13 @@ def parse_args(): 'alias_protein': 'object', 'hgvs_aa_mutation': 'object', 'hgvs_alias': 'object', - 'protein_name': 'object' + 'protein_name': 'object', + 'gene_name': 'object', + 'gene_symbol': 'object', + 'mat_pep': 'object', + 'protein_symbol': 'object', + 'pos': 'int64', # Assuming 'pos' is an integer column + 'lineages': 'object' } ) # fillna to make groupby() work From d9edd7572337f4ede50ef1881810ed1ee2117878 Mon Sep 17 00:00:00 2001 From: miseminger Date: Fri, 13 Dec 2024 12:53:29 -0800 Subject: [PATCH 141/161] update dtypes to match index columns --- bin/merge_indices.py | 14 ++++++++------ 1 file changed, 8 insertions(+), 6 deletions(-) diff --git a/bin/merge_indices.py b/bin/merge_indices.py index 66fddd01..eb610ce2 100755 --- a/bin/merge_indices.py +++ b/bin/merge_indices.py @@ -54,16 +54,18 @@ def parse_args(): indices_to_merge, sep='\t', dtype={ - 'alias': 'object', - 'alias_protein': 'object', + 'pos': 'int64', # Assuming 'pos' is an integer column + 'mutation': 'object', 'hgvs_aa_mutation': 'object', - 'hgvs_alias': 'object', - 'protein_name': 'object', + 'hgvs_nt_mutation': 'object', 'gene_name': 'object', 'gene_symbol': 'object', - 'mat_pep': 'object', + 'protein_name': 'object', 'protein_symbol': 'object', - 'pos': 'int64', # Assuming 'pos' is an integer column + 'alias': 'object', + 'hgvs_alias': 'object', + 'mat_pep': 'object', + 'pokay_annotation': 'object', 'lineages': 'object' } ) From 058630ddb820610992cef9a26a21dea96dfe47a9 Mon Sep 17 00:00:00 2001 From: miseminger Date: Fri, 13 Dec 2024 13:04:57 -0800 Subject: [PATCH 142/161] update index column names --- bin/merge_logfiles.py | 6 +++--- 1 file changed, 3 insertions(+), 3 deletions(-) diff --git a/bin/merge_logfiles.py b/bin/merge_logfiles.py index b94832ee..59318923 100755 --- a/bin/merge_logfiles.py +++ b/bin/merge_logfiles.py @@ -64,10 +64,10 @@ def parse_args(): # convert original_index to match the logfile columns # read index into pandas df og_index = pd.read_csv(original_index, sep='\t').fillna('n/a') - # fill in 'new_mutations' column like: "gene:mutation" - og_index['new_mutations'] = og_index["gene"] + ":" + og_index["mutation"] + # fill in 'new_mutations' column like: "protein:mutation" + og_index['new_mutations'] = og_index["protein_symbol"] + ":" + og_index["mutation"] # for orf1ab mutations, fill in 'new_mutations' column like: "gene:mutation / nsp:alias" - og_index.loc[og_index['alias']!='n/a', 'new_mutations'] = og_index['new_mutations'] + " / " + og_index["alias_protein"] + ":" + og_index["alias"] + og_index.loc[og_index['alias']!='n/a', 'new_mutations'] = og_index['new_mutations'] + " / " + og_index["mat_pep"] + ":" + og_index["alias"] # drop duplicates (there shouldn't be any) og_index = og_index[['pos', 'new_mutations', 'lineages']].drop_duplicates() # drop any NaN rows From 40caf5ee2e81f4b967f9992f7d525e2cf8ea3410 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Fri, 13 Dec 2024 14:46:55 -0800 Subject: [PATCH 143/161] archived script --- bin/{ => archive}/update_index_and_logfile.py | 0 1 file changed, 0 insertions(+), 0 deletions(-) rename bin/{ => archive}/update_index_and_logfile.py (100%) diff --git a/bin/update_index_and_logfile.py b/bin/archive/update_index_and_logfile.py similarity index 100% rename from bin/update_index_and_logfile.py rename to bin/archive/update_index_and_logfile.py From 8679c248ebe4f0f997485b40a0c889b3b634e9f3 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 15:43:06 -0800 Subject: [PATCH 144/161] updated config --- .gitignore | 1 - conf/eagle.config | 35 +++++++++++++++++++++++++++++++++++ conf/profiles.config | 4 ++-- covidmvp_clinical_params.yaml | 9 ++++----- nextflow.config | 35 ----------------------------------- 5 files changed, 41 insertions(+), 43 deletions(-) diff --git a/.gitignore b/.gitignore index beb9fbed..fdd7e974 100644 --- a/.gitignore +++ b/.gitignore @@ -13,7 +13,6 @@ weekly* bin/__* *.sh latest* -data/* *.fa.xz *.gz hMPXV_* diff --git a/conf/eagle.config b/conf/eagle.config index 9163f27d..bdb6055d 100644 --- a/conf/eagle.config +++ b/conf/eagle.config @@ -24,6 +24,41 @@ params { process { clusterOptions = { "--account=def-sponsor00" } executor = 'slurm' + + withName: 'DOWNLOAD_VIRALAI_METADATA' { + memory = '16 GB' // Increase this value as needed + } + withName: 'PROCESS_VIRALAI_METADATA' { + memory = '16 GB' // Increase this value as needed + } + withName: 'METADATA_HARMONIZER' { + memory = '16 GB' // Increase this value as needed + } + withName: 'EXTRACTVARIANTS' { + memory = '16 GB' // Increase this value as needed + } + withName: 'EXTRACTMETADATA' { + memory = '16 GB' // Increase this value as needed + } + withName: 'MINIMAP2_ALIGN' { + memory = '32 GB' // Increase this value as needed + } + withName: 'SAMTOOLS_SORT' { + memory = '16 GB' // Increase this value as needed + } + withName: 'SAMTOOLS_STATS' { + memory = '16 GB' // Increase this value as needed + } + withName: 'FREEBAYES' { + memory = '84 GB' // Increase this value as needed + } + withName: 'MERGE_LOGFILES' { + memory = '32 GB' // Increase this value as needed + } + withName: 'MERGE_INDICES' { + memory = '32 GB' // Increase this value as needed + } + } executor { diff --git a/conf/profiles.config b/conf/profiles.config index 40237531..4d1d26f9 100644 --- a/conf/profiles.config +++ b/conf/profiles.config @@ -65,8 +65,8 @@ profiles { executor.memory = 60.GB } wave { - enabled = true - strategy = ['singularity'] + wave.enabled = true + wave.strategy = ['singularity'] } eagle { includeConfig 'eagle.config' } } \ No newline at end of file diff --git a/covidmvp_clinical_params.yaml b/covidmvp_clinical_params.yaml index f5b8be81..15c37603 100644 --- a/covidmvp_clinical_params.yaml +++ b/covidmvp_clinical_params.yaml @@ -1,16 +1,15 @@ mode: "reference" -seq: "/scratch/group_share/nextflow_workdir/mzanwar/93/c3c398c03ff4a68a688446f139cda0/2024-11-15T02%3A00%3A02Z.5f384c10-e08e-4567-ae6e-a1e26035e4b3.multi.fa.xz" -meta: "/scratch/group_share/nextflow_workdir/mzanwar/2d/63961dce3ce007283f6f9f71413044/viralai_metadata_processed.csv.gz" grouping_criteria: "lineage" -viralai: false +viralai: true virusseq: true -virusseq_update: false +virusseq_update: true skip_classification: true skip_postprocessing: false skip_posting: true skip_harmonize: false start_date: "2020-01-01" -end_date: "2024-12-02" +end_date: "2024-12-13" metadata_source: "ViralAi_EpiCoV" metadata_config: "/project/def-virusmvp/mzanwar/nf-ncov-voc/assets/metadata_conf/metadata.yaml" outdir: "/project/def-virusmvp/mzanwar/nf-ncov-voc/results/covidmvp" +mutation_indexfile: "/project/def-virusmvp/mzanwar/nf-ncov-voc/results/covidmvp/covidmvp-2024-12-12/MUTATION_INDEX/2024-12-12.index.tsv" diff --git a/nextflow.config b/nextflow.config index f92b67b8..979927bb 100644 --- a/nextflow.config +++ b/nextflow.config @@ -17,41 +17,6 @@ includeConfig 'conf/nf-ncov-voc.config' includeConfig 'conf/profiles.config' includeConfig 'conf/modules.config' -process { - withName: 'PROCESS_VIRALAI_METADATA' { - memory = '16 GB' // Increase this value as needed - } - withName: 'METADATA_HARMONIZER' { - memory = '16 GB' // Increase this value as needed - } - withName: 'EXTRACTVARIANTS' { - memory = '16 GB' // Increase this value as needed - } - withName: 'EXTRACTMETADATA' { - memory = '16 GB' // Increase this value as needed - } - withName: 'MINIMAP2_ALIGN' { - memory = '16 GB' // Increase this value as needed - } - withName: 'SAMTOOLS_SORT' { - memory = '16 GB' // Increase this value as needed - } - withName: 'SAMTOOLS_STATS' { - memory = '16 GB' // Increase this value as needed - } - withName: 'FREEBAYES' { - memory = '64 GB' // Increase this value as needed - } - withName: 'MERGE_LOGFILES' { - memory = '32 GB' // Increase this value as needed - } - withName: 'MERGE_INDICES' { - memory = '32 GB' // Increase this value as needed - } - - - -} // Export these variables to prevent local Python/R libraries from conflicting with those in the container env { From 097770cf26275a1f93bc37c17c234d169d51ab6a Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 15:43:26 -0800 Subject: [PATCH 145/161] fixed covidmvp user uploaded error --- workflows/covidmvp.nf | 1 + 1 file changed, 1 insertion(+) diff --git a/workflows/covidmvp.nf b/workflows/covidmvp.nf index 95c8381d..30868a3e 100644 --- a/workflows/covidmvp.nf +++ b/workflows/covidmvp.nf @@ -24,6 +24,7 @@ workflow COVIDMVP { main: //ch_voc = Channel.empty() + metadata = Channel.empty() skip_variant_calling = false if (params.viralai) { VIRALAI() From acc7b7f3d4ba966dfdc3e21c3917adc9e9c04b9e Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 15:43:54 -0800 Subject: [PATCH 146/161] updated user uploaded test --- covidmvp_user.yaml | 4 +--- 1 file changed, 1 insertion(+), 3 deletions(-) diff --git a/covidmvp_user.yaml b/covidmvp_user.yaml index 26f16958..868bbb33 100644 --- a/covidmvp_user.yaml +++ b/covidmvp_user.yaml @@ -1,7 +1,5 @@ prefix: "covidmvp-user" mode: "user" -viral_aligner: "minimap2" -viralai: false skip_classification: true skip_postprocessing: true skip_posting: true @@ -9,5 +7,5 @@ skip_harmonize: true start_date: "2020-01-01" end_date: "2024-12-01" outdir: "results/covidmvp" -seq: "/project/def-virusmvp/mzanwar/nf-ncov-voc/data/sars-cov-2/sars-cov-2_test_data_1x.fa" +seq: "/project/def-virusmvp/mzanwar/nf-ncov-voc/test_data/sars-cov-2/sars-cov-2_test_data_1x.fa" # seq: "data/viralai_test.vcf" From 279200f607a5a7e2bef65d96d10fba5d1f9930e1 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 15:57:32 -0800 Subject: [PATCH 147/161] updated preprocessing --- subworkflows/local/virusmvp_preprocessing.nf | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/subworkflows/local/virusmvp_preprocessing.nf b/subworkflows/local/virusmvp_preprocessing.nf index 02faead1..2e15fa4b 100644 --- a/subworkflows/local/virusmvp_preprocessing.nf +++ b/subworkflows/local/virusmvp_preprocessing.nf @@ -8,7 +8,7 @@ include { SEQKIT_GREP } from '../../modules/nf-core/seqkit/grep/main' workflow PREPROCESSING { take: - metadata + metadata sequences main: From bb23c62b21d194355e4630885bc038b75051136d Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 16:15:58 -0800 Subject: [PATCH 148/161] updated github actions testing --- .github/workflows/nextflow_CI.yml | 22 ++++++++++++++++++++++ .gitignore | 4 ---- 2 files changed, 22 insertions(+), 4 deletions(-) create mode 100644 .github/workflows/nextflow_CI.yml diff --git a/.github/workflows/nextflow_CI.yml b/.github/workflows/nextflow_CI.yml new file mode 100644 index 00000000..d6b51d0d --- /dev/null +++ b/.github/workflows/nextflow_CI.yml @@ -0,0 +1,22 @@ +name: Nextflow CI + +on: + push: + branches: + - development + +jobs: + test: + name: Run pipeline test + runs-on: ubuntu-latest + steps: + - uses: actions/checkout@v3 + + - name: Install Nextflow + run: | + wget -qO- get.nextflow.io | bash + sudo mv nextflow /usr/local/bin/ + + - name: Run pipeline test + run: | + nextflow run main.nf -profile docker -profile singularity,eagle --prefix "covidmvp-user-$(date +%Y-%m-%d)" -params-file covidmvp_user.yaml diff --git a/.gitignore b/.gitignore index fdd7e974..3bbbacae 100644 --- a/.gitignore +++ b/.gitignore @@ -1,11 +1,7 @@ .nextflow* -work/* results/* .idea/* -.github/data/metadata -.github/data/sequence .DS_store -testing/* *.ipynb weekly* *.error From 62ef05d032de6dc3b3c427ac9c6e8ddd2e775ace Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 16:16:48 -0800 Subject: [PATCH 149/161] fixed actions typo --- .github/workflows/nextflow_CI.yml | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/.github/workflows/nextflow_CI.yml b/.github/workflows/nextflow_CI.yml index d6b51d0d..78e361ea 100644 --- a/.github/workflows/nextflow_CI.yml +++ b/.github/workflows/nextflow_CI.yml @@ -19,4 +19,4 @@ jobs: - name: Run pipeline test run: | - nextflow run main.nf -profile docker -profile singularity,eagle --prefix "covidmvp-user-$(date +%Y-%m-%d)" -params-file covidmvp_user.yaml + nextflow run main.nf -profile docker --prefix "covidmvp-user-$(date +%Y-%m-%d)" -params-file covidmvp_user.yaml From de0348fe2262af7ceaf6589802a1c33475fded58 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 16:19:21 -0800 Subject: [PATCH 150/161] updated relative path to seq file --- covidmvp_user.yaml | 3 +-- 1 file changed, 1 insertion(+), 2 deletions(-) diff --git a/covidmvp_user.yaml b/covidmvp_user.yaml index 868bbb33..d3d241ca 100644 --- a/covidmvp_user.yaml +++ b/covidmvp_user.yaml @@ -5,7 +5,6 @@ skip_postprocessing: true skip_posting: true skip_harmonize: true start_date: "2020-01-01" -end_date: "2024-12-01" outdir: "results/covidmvp" -seq: "/project/def-virusmvp/mzanwar/nf-ncov-voc/test_data/sars-cov-2/sars-cov-2_test_data_1x.fa" +seq: "test_data/sars-cov-2/sars-cov-2_test_data_1x.fa" # seq: "data/viralai_test.vcf" From 23a56e74010431a7f051f6edfc2ce188e6c87cf2 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 23:31:39 -0800 Subject: [PATCH 151/161] updated workflow params and conf --- .github/workflows/nextflow_CI.yml | 21 ++++++++++++++++++--- conf/profiles.config | 1 - covidmvp_clinical_params.yaml | 13 ++++++------- covidmvp_user.yaml | 1 - 4 files changed, 24 insertions(+), 12 deletions(-) diff --git a/.github/workflows/nextflow_CI.yml b/.github/workflows/nextflow_CI.yml index 78e361ea..0808b4c5 100644 --- a/.github/workflows/nextflow_CI.yml +++ b/.github/workflows/nextflow_CI.yml @@ -6,8 +6,8 @@ on: - development jobs: - test: - name: Run pipeline test + test_sarscov2_user: + name: Run pipeline test (user) runs-on: ubuntu-latest steps: - uses: actions/checkout@v3 @@ -17,6 +17,21 @@ jobs: wget -qO- get.nextflow.io | bash sudo mv nextflow /usr/local/bin/ - - name: Run pipeline test + - name: Run pipeline test (default) run: | nextflow run main.nf -profile docker --prefix "covidmvp-user-$(date +%Y-%m-%d)" -params-file covidmvp_user.yaml + + test_sarscov2_reference: + name: Run pipeline test (reference) + runs-on: ubuntu-latest + steps: + - uses: actions/checkout@v3 + + - name: Install Nextflow + run: | + wget -qO- get.nextflow.io | bash + sudo mv nextflow /usr/local/bin/ + + - name: Run pipeline test (alternative) + run: | + nextflow run main.nf -profile docker --prefix "covidmvp-$(date +%Y-%m-%d)" -params-file covidmvp_clinical_params.yaml diff --git a/conf/profiles.config b/conf/profiles.config index 4d1d26f9..f6eaed47 100644 --- a/conf/profiles.config +++ b/conf/profiles.config @@ -20,7 +20,6 @@ profiles { } docker { docker.enabled = true - docker.userEmulation = true singularity.enabled = false podman.enabled = false shifter.enabled = false diff --git a/covidmvp_clinical_params.yaml b/covidmvp_clinical_params.yaml index 15c37603..28f26850 100644 --- a/covidmvp_clinical_params.yaml +++ b/covidmvp_clinical_params.yaml @@ -1,15 +1,14 @@ mode: "reference" grouping_criteria: "lineage" -viralai: true +viralai: false virusseq: true -virusseq_update: true +virusseq_update: false skip_classification: true skip_postprocessing: false skip_posting: true -skip_harmonize: false +skip_harmonize: true start_date: "2020-01-01" -end_date: "2024-12-13" +end_date: "(date +%Y-%m-%d)" metadata_source: "ViralAi_EpiCoV" -metadata_config: "/project/def-virusmvp/mzanwar/nf-ncov-voc/assets/metadata_conf/metadata.yaml" -outdir: "/project/def-virusmvp/mzanwar/nf-ncov-voc/results/covidmvp" -mutation_indexfile: "/project/def-virusmvp/mzanwar/nf-ncov-voc/results/covidmvp/covidmvp-2024-12-12/MUTATION_INDEX/2024-12-12.index.tsv" +metadata_config: "metadata_conf/metadata.yaml" +outdir: "results/covidmvp" diff --git a/covidmvp_user.yaml b/covidmvp_user.yaml index d3d241ca..9e7825a3 100644 --- a/covidmvp_user.yaml +++ b/covidmvp_user.yaml @@ -4,7 +4,6 @@ skip_classification: true skip_postprocessing: true skip_posting: true skip_harmonize: true -start_date: "2020-01-01" outdir: "results/covidmvp" seq: "test_data/sars-cov-2/sars-cov-2_test_data_1x.fa" # seq: "data/viralai_test.vcf" From a540a570a5cbd0625dd4c2f0f8d3502d498e3a09 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 23:33:18 -0800 Subject: [PATCH 152/161] updated test data for reference --- ...sars-cov-2-test-reference-metadata-ids.txt | 770 ++++++++++++++++++ .../sars-cov-2-test-reference-metadata.tsv.gz | Bin 0 -> 10436 bytes .../sars-cov-2-test-reference-seq.fa.gz | Bin 0 -> 2202380 bytes 3 files changed, 770 insertions(+) create mode 100644 test_data/sars-cov-2/sars-cov-2-test-reference-metadata-ids.txt create mode 100644 test_data/sars-cov-2/sars-cov-2-test-reference-metadata.tsv.gz create mode 100644 test_data/sars-cov-2/sars-cov-2-test-reference-seq.fa.gz diff --git a/test_data/sars-cov-2/sars-cov-2-test-reference-metadata-ids.txt b/test_data/sars-cov-2/sars-cov-2-test-reference-metadata-ids.txt new file mode 100644 index 00000000..34b15ffd --- /dev/null +++ b/test_data/sars-cov-2/sars-cov-2-test-reference-metadata-ids.txt @@ -0,0 +1,770 @@ +isolate +hCoV-19/Canada/QC-L00608997001/2023 +hCoV-19/Canada/QC-L00578336001/2023 +hCoV-19/Canada/QC-L00608993001/2023 +hCoV-19/Canada/QC-L00608904001/2023 +hCoV-19/Canada/QC-L00598510001/2023 +hCoV-19/Canada/QC-L00579897001/2023 +hCoV-19/Canada/QC-L00609849001/2023 +hCoV-19/Canada/QC-L00607395001/2023 +hCoV-19/Canada/QC-L00609846001/2023 +hCoV-19/Canada/QC-L00600191001/2023 +hCoV-19/Canada/QC-L00609004001/2023 +hCoV-19/Canada/ON-PHL-202404757/2024 +hCoV-19/Canada/ON-PHL-202404791/2024 +hCoV-19/Canada/AB-ABPHL-116155/2024 +hCoV-19/Canada/BC-BCCDC-721591/2024 +hCoV-19/Canada/QC-L00703056001/2024 +hCoV-19/Canada/BC-BCCDC-726117/2024 +hCoV-19/Canada/AB-ABPHL-116169/2024 +hCoV-19/Canada/BC-BCCDC-724854/2024 +hCoV-19/Canada/ON-PHL-202404976/2024 +hCoV-19/Canada/BC-BCCDC-727089/2024 +hCoV-19/Canada/BC-BCCDC-722598/2024 +hCoV-19/Canada/BC-BCCDC-723307/2024 +hCoV-19/Canada/AB-ABPHL-116168/2024 +hCoV-19/Canada/ON-PHL-202404818/2024 +hCoV-19/Canada/BC-BCCDC-726138/2024 +hCoV-19/Canada/ON-PHL-202404971/2024 +hCoV-19/Canada/ON-PHL-202404773/2024 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zX8aX;AX%PFiQhUVExJ3&1Itd&l!J-rt}nU?`l8=$Jnx~`b!v1HX*d!PJF-b5e&@z_ zd^5t1O=l?};MV{;qn|5xT8ET)R;PU{#3oe_9?foP1z*&SkSY~1M7g##$Lu_hQN}jyD|nt?%AD#a%BY zz3s3~8Mzr;#>KeXvr~R7Ld`rpsEJ6wvk&5^axlpsMK_+d+I998rz@*+o24W2wj*St{_pFI>dzKeVJr$g1sBlu9y87R8Up$h9U^Rq$f#_;;S zwP$+`8*iEWQx|`glSzWg^DR8bEF(_7^3?a%1@Q)2g(u`6J(j-&ogOc|| z5_9%{_D0n)08Cn5(+9%oy~pS`qG#N=Pc$vzJ%~#2WsA5Rsfo+V{weim)X3{V1wO>T z%nKpxIv29uaTn@FKo0_fY`TF=0lNII8Tz@gz3b%JeTsl^7My4MBtJ}KD#M?@C3LP( zQI9vU(ZlcXxQs((>fqSEpSh=~c&`qTgzl}XshT#?A{&=^i2(3h`0 zs!ygDtQTLHUNUQootKRIRB0^TBP6AXmxFX)et#8C>hf>5f|FD?j;!3?eeaZ5#vwzR zakfRkT|cvtsZ`EN$ZRb(fNTX-j(^tlmNzz?3ljJ) zcDJes&PETsO4kH#_v$}9t5TnQ6L>x)QZ@Lnkesv3y@wM-fINVc*@51gdRcrC7P-r1 z6IUVqk**V)P8^rMYmukS-8W#-)bw&EZR_wNXFG*T2Bu5=6Oy50dl}tr(jaOw!#cu_ z=uJdqq4Ggs)W`M86zB7R0)>_z;4jbk-;0f>RIG)M{BDdEXwLo5;WN13{lU{lYZ8^? znTSW67dyvNM0?NMveDVL!LFGW1e=mw`>Cx#Dn_>#%Ygd6e!iUf)8OxK1vV@{mIRF9bu2KL7v# literal 0 HcmV?d00001 From 2adca4ced65f653a0d8bc4de03353b3df8d7f7f4 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 23:36:39 -0800 Subject: [PATCH 153/161] updated test data --- covidmvp_clinical_params.yaml | 2 ++ 1 file changed, 2 insertions(+) diff --git a/covidmvp_clinical_params.yaml b/covidmvp_clinical_params.yaml index 28f26850..6c440727 100644 --- a/covidmvp_clinical_params.yaml +++ b/covidmvp_clinical_params.yaml @@ -12,3 +12,5 @@ end_date: "(date +%Y-%m-%d)" metadata_source: "ViralAi_EpiCoV" metadata_config: "metadata_conf/metadata.yaml" outdir: "results/covidmvp" +meta: "test_data/sars-cov-2/sars-cov-2-test-reference-metadata.tsv.gz" +seq: "test_data/sars-cov-2/sars-cov-2-test-reference-seq.fa.gz" From 4f8583af58f8983b3f52aa2c4a621ee5d5e59a90 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 23:43:51 -0800 Subject: [PATCH 154/161] update module docker containers --- modules/local/convertgff2json.nf | 2 +- modules/local/extractMetadata.nf | 2 +- modules/local/extractVariants.nf | 2 +- modules/local/harmonize_metadata.nf | 4 ++-- modules/local/merge_classification_report.nf | 2 +- modules/local/splitmutations_gvf.nf | 2 +- modules/local/splitmutations_pokay.nf | 2 +- modules/local/vcftogvf.nf | 2 +- 8 files changed, 9 insertions(+), 9 deletions(-) diff --git a/modules/local/convertgff2json.nf b/modules/local/convertgff2json.nf index 4dfa2a38..9f318f76 100644 --- a/modules/local/convertgff2json.nf +++ b/modules/local/convertgff2json.nf @@ -8,7 +8,7 @@ process CONVERTGFFTOJSON { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'amancevice/pandas:1.4.3'}" + : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" input: tuple val(meta), path(gff) diff --git a/modules/local/extractMetadata.nf b/modules/local/extractMetadata.nf index f892978a..005c9de8 100644 --- a/modules/local/extractMetadata.nf +++ b/modules/local/extractMetadata.nf @@ -3,7 +3,7 @@ process EXTRACTMETADATA { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'amancevice/pandas:1.4.3'}" + : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" input: tuple val(meta), path(metadata) diff --git a/modules/local/extractVariants.nf b/modules/local/extractVariants.nf index 238c302d..b861c55d 100644 --- a/modules/local/extractVariants.nf +++ b/modules/local/extractVariants.nf @@ -3,7 +3,7 @@ process EXTRACTVARIANTS { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'amancevice/pandas:1.4.3'}" + : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" input: tuple val(meta), path(variants) diff --git a/modules/local/harmonize_metadata.nf b/modules/local/harmonize_metadata.nf index 7612a185..e5f4cbd6 100644 --- a/modules/local/harmonize_metadata.nf +++ b/modules/local/harmonize_metadata.nf @@ -3,8 +3,8 @@ process METADATA_HARMONIZER { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container - ? 'docker://pandas/pandas:pip-all' - : 'pandas/pandas:pip-all'}" + ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' + : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" input: tuple val(meta), path(metadata) diff --git a/modules/local/merge_classification_report.nf b/modules/local/merge_classification_report.nf index b40a2704..f9a6fb6d 100644 --- a/modules/local/merge_classification_report.nf +++ b/modules/local/merge_classification_report.nf @@ -3,7 +3,7 @@ process MERGE_CLASSIFFICATION_METADATA { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'amancevice/pandas:1.4.3'}" + : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" input: tuple val(meta), path(metadata) diff --git a/modules/local/splitmutations_gvf.nf b/modules/local/splitmutations_gvf.nf index 3d6c6c23..5bcf46eb 100644 --- a/modules/local/splitmutations_gvf.nf +++ b/modules/local/splitmutations_gvf.nf @@ -5,7 +5,7 @@ process NCOVSPLITMUTATIONSGVF { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'amancevice/pandas:1.4.3'}" + : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" input: tuple val(meta), path(gvf) diff --git a/modules/local/splitmutations_pokay.nf b/modules/local/splitmutations_pokay.nf index 07f4cdda..73961839 100644 --- a/modules/local/splitmutations_pokay.nf +++ b/modules/local/splitmutations_pokay.nf @@ -5,7 +5,7 @@ process NCOVSPLITMUTATIONSPOKAY { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'amancevice/pandas:1.4.3'}" + : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" input: tuple val(meta), path(annotations) diff --git a/modules/local/vcftogvf.nf b/modules/local/vcftogvf.nf index 4b8d25ee..98819953 100644 --- a/modules/local/vcftogvf.nf +++ b/modules/local/vcftogvf.nf @@ -3,7 +3,7 @@ process VCFTOGVF { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'amancevice/pandas:1.4.3'}" + : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" input: tuple val(meta), path(vcf) From fc4a5e946fd1e821f60e85f185723a9e767de285 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 23:46:49 -0800 Subject: [PATCH 155/161] update containers --- conf/profiles.config | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/conf/profiles.config b/conf/profiles.config index f6eaed47..e0d4cb1c 100644 --- a/conf/profiles.config +++ b/conf/profiles.config @@ -65,7 +65,7 @@ profiles { } wave { wave.enabled = true - wave.strategy = ['singularity'] + wave.strategy = ['singularity', 'container'] } eagle { includeConfig 'eagle.config' } } \ No newline at end of file From dce1f37be2fc79948853be95d7a508f2b90e99e6 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 23:48:27 -0800 Subject: [PATCH 156/161] update workflow --- .github/workflows/nextflow_CI.yml | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/.github/workflows/nextflow_CI.yml b/.github/workflows/nextflow_CI.yml index 0808b4c5..310f7e9c 100644 --- a/.github/workflows/nextflow_CI.yml +++ b/.github/workflows/nextflow_CI.yml @@ -34,4 +34,4 @@ jobs: - name: Run pipeline test (alternative) run: | - nextflow run main.nf -profile docker --prefix "covidmvp-$(date +%Y-%m-%d)" -params-file covidmvp_clinical_params.yaml + nextflow run main.nf -profile singularity --prefix "covidmvp-$(date +%Y-%m-%d)" -params-file covidmvp_clinical_params.yaml From bdc1cd97bdbd59d3e94a76f789de46955ad90237 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 23:50:47 -0800 Subject: [PATCH 157/161] update workflow singularity --- .github/workflows/nextflow_CI.yml | 38 ++++++++++++++++++++++++++++--- 1 file changed, 35 insertions(+), 3 deletions(-) diff --git a/.github/workflows/nextflow_CI.yml b/.github/workflows/nextflow_CI.yml index 310f7e9c..b54410ea 100644 --- a/.github/workflows/nextflow_CI.yml +++ b/.github/workflows/nextflow_CI.yml @@ -17,9 +17,25 @@ jobs: wget -qO- get.nextflow.io | bash sudo mv nextflow /usr/local/bin/ - - name: Run pipeline test (default) + - name: Install Singularity run: | - nextflow run main.nf -profile docker --prefix "covidmvp-user-$(date +%Y-%m-%d)" -params-file covidmvp_user.yaml + sudo apt-get update && sudo apt-get install -y \ + build-essential \ + libssl-dev \ + uuid-dev \ + libgpgme11-dev \ + squashfs-tools \ + libseccomp-dev \ + wget \ + pkg-config \ + git \ + cryptsetup + wget https://github.com/sylabs/singularity/releases/download/v3.10.0/singularity-ce_3.10.0-focal_amd64.deb + sudo dpkg -i singularity-ce_3.10.0-focal_amd64.deb + + - name: Run pipeline test (user) + run: | + nextflow run main.nf -profile singularity --prefix "covidmvp-user-$(date +%Y-%m-%d)" -params-file covidmvp_user.yaml test_sarscov2_reference: name: Run pipeline test (reference) @@ -32,6 +48,22 @@ jobs: wget -qO- get.nextflow.io | bash sudo mv nextflow /usr/local/bin/ - - name: Run pipeline test (alternative) + - name: Install Singularity + run: | + sudo apt-get update && sudo apt-get install -y \ + build-essential \ + libssl-dev \ + uuid-dev \ + libgpgme11-dev \ + squashfs-tools \ + libseccomp-dev \ + wget \ + pkg-config \ + git \ + cryptsetup + wget https://github.com/sylabs/singularity/releases/download/v3.10.0/singularity-ce_3.10.0-focal_amd64.deb + sudo dpkg -i singularity-ce_3.10.0-focal_amd64.deb + + - name: Run pipeline test (reference) run: | nextflow run main.nf -profile singularity --prefix "covidmvp-$(date +%Y-%m-%d)" -params-file covidmvp_clinical_params.yaml From 770e25035c5042bce3e86cbaff2beaf07262cb68 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Sun, 15 Dec 2024 23:58:48 -0800 Subject: [PATCH 158/161] update workflow --- .github/workflows/nextflow_CI.yml | 36 ++------------------ conf/profiles.config | 2 +- covidmvp_clinical_params.yaml | 1 - modules/local/convertgff2json.nf | 2 +- modules/local/extractMetadata.nf | 2 +- modules/local/extractVariants.nf | 2 +- modules/local/harmonize_metadata.nf | 2 +- modules/local/merge_classification_report.nf | 2 +- modules/local/splitmutations_gvf.nf | 2 +- modules/local/splitmutations_pokay.nf | 2 +- modules/local/vcftogvf.nf | 2 +- 11 files changed, 11 insertions(+), 44 deletions(-) diff --git a/.github/workflows/nextflow_CI.yml b/.github/workflows/nextflow_CI.yml index b54410ea..d5ca39bb 100644 --- a/.github/workflows/nextflow_CI.yml +++ b/.github/workflows/nextflow_CI.yml @@ -17,25 +17,9 @@ jobs: wget -qO- get.nextflow.io | bash sudo mv nextflow /usr/local/bin/ - - name: Install Singularity - run: | - sudo apt-get update && sudo apt-get install -y \ - build-essential \ - libssl-dev \ - uuid-dev \ - libgpgme11-dev \ - squashfs-tools \ - libseccomp-dev \ - wget \ - pkg-config \ - git \ - cryptsetup - wget https://github.com/sylabs/singularity/releases/download/v3.10.0/singularity-ce_3.10.0-focal_amd64.deb - sudo dpkg -i singularity-ce_3.10.0-focal_amd64.deb - - name: Run pipeline test (user) run: | - nextflow run main.nf -profile singularity --prefix "covidmvp-user-$(date +%Y-%m-%d)" -params-file covidmvp_user.yaml + nextflow run main.nf -profile docker --prefix "covidmvp-user-$(date +%Y-%m-%d)" -params-file covidmvp_user.yaml test_sarscov2_reference: name: Run pipeline test (reference) @@ -48,22 +32,6 @@ jobs: wget -qO- get.nextflow.io | bash sudo mv nextflow /usr/local/bin/ - - name: Install Singularity - run: | - sudo apt-get update && sudo apt-get install -y \ - build-essential \ - libssl-dev \ - uuid-dev \ - libgpgme11-dev \ - squashfs-tools \ - libseccomp-dev \ - wget \ - pkg-config \ - git \ - cryptsetup - wget https://github.com/sylabs/singularity/releases/download/v3.10.0/singularity-ce_3.10.0-focal_amd64.deb - sudo dpkg -i singularity-ce_3.10.0-focal_amd64.deb - - name: Run pipeline test (reference) run: | - nextflow run main.nf -profile singularity --prefix "covidmvp-$(date +%Y-%m-%d)" -params-file covidmvp_clinical_params.yaml + nextflow run main.nf -profile docker --prefix "covidmvp-$(date +%Y-%m-%d)" --end_date $(date +%Y-%m-%d) -params-file covidmvp_clinical_params.yaml diff --git a/conf/profiles.config b/conf/profiles.config index e0d4cb1c..f6eaed47 100644 --- a/conf/profiles.config +++ b/conf/profiles.config @@ -65,7 +65,7 @@ profiles { } wave { wave.enabled = true - wave.strategy = ['singularity', 'container'] + wave.strategy = ['singularity'] } eagle { includeConfig 'eagle.config' } } \ No newline at end of file diff --git a/covidmvp_clinical_params.yaml b/covidmvp_clinical_params.yaml index 6c440727..ec60be66 100644 --- a/covidmvp_clinical_params.yaml +++ b/covidmvp_clinical_params.yaml @@ -8,7 +8,6 @@ skip_postprocessing: false skip_posting: true skip_harmonize: true start_date: "2020-01-01" -end_date: "(date +%Y-%m-%d)" metadata_source: "ViralAi_EpiCoV" metadata_config: "metadata_conf/metadata.yaml" outdir: "results/covidmvp" diff --git a/modules/local/convertgff2json.nf b/modules/local/convertgff2json.nf index 9f318f76..4dfa2a38 100644 --- a/modules/local/convertgff2json.nf +++ b/modules/local/convertgff2json.nf @@ -8,7 +8,7 @@ process CONVERTGFFTOJSON { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" + : 'amancevice/pandas:1.4.3'}" input: tuple val(meta), path(gff) diff --git a/modules/local/extractMetadata.nf b/modules/local/extractMetadata.nf index 005c9de8..f892978a 100644 --- a/modules/local/extractMetadata.nf +++ b/modules/local/extractMetadata.nf @@ -3,7 +3,7 @@ process EXTRACTMETADATA { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" + : 'amancevice/pandas:1.4.3'}" input: tuple val(meta), path(metadata) diff --git a/modules/local/extractVariants.nf b/modules/local/extractVariants.nf index b861c55d..238c302d 100644 --- a/modules/local/extractVariants.nf +++ b/modules/local/extractVariants.nf @@ -3,7 +3,7 @@ process EXTRACTVARIANTS { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" + : 'amancevice/pandas:1.4.3'}" input: tuple val(meta), path(variants) diff --git a/modules/local/harmonize_metadata.nf b/modules/local/harmonize_metadata.nf index e5f4cbd6..de40df21 100644 --- a/modules/local/harmonize_metadata.nf +++ b/modules/local/harmonize_metadata.nf @@ -4,7 +4,7 @@ process METADATA_HARMONIZER { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" + : 'amancevice/pandas:1.4.3'}" input: tuple val(meta), path(metadata) diff --git a/modules/local/merge_classification_report.nf b/modules/local/merge_classification_report.nf index f9a6fb6d..b40a2704 100644 --- a/modules/local/merge_classification_report.nf +++ b/modules/local/merge_classification_report.nf @@ -3,7 +3,7 @@ process MERGE_CLASSIFFICATION_METADATA { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" + : 'amancevice/pandas:1.4.3'}" input: tuple val(meta), path(metadata) diff --git a/modules/local/splitmutations_gvf.nf b/modules/local/splitmutations_gvf.nf index 5bcf46eb..3d6c6c23 100644 --- a/modules/local/splitmutations_gvf.nf +++ b/modules/local/splitmutations_gvf.nf @@ -5,7 +5,7 @@ process NCOVSPLITMUTATIONSGVF { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" + : 'amancevice/pandas:1.4.3'}" input: tuple val(meta), path(gvf) diff --git a/modules/local/splitmutations_pokay.nf b/modules/local/splitmutations_pokay.nf index 73961839..07f4cdda 100644 --- a/modules/local/splitmutations_pokay.nf +++ b/modules/local/splitmutations_pokay.nf @@ -5,7 +5,7 @@ process NCOVSPLITMUTATIONSPOKAY { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" + : 'amancevice/pandas:1.4.3'}" input: tuple val(meta), path(annotations) diff --git a/modules/local/vcftogvf.nf b/modules/local/vcftogvf.nf index 98819953..4b8d25ee 100644 --- a/modules/local/vcftogvf.nf +++ b/modules/local/vcftogvf.nf @@ -3,7 +3,7 @@ process VCFTOGVF { conda "conda-forge::pandas=1.4.3" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'https://depot.galaxyproject.org/singularity/pandas:1.4.3' - : 'community.wave.seqera.io/library/pip_pandas:f80b46869e03f6ef'}" + : 'amancevice/pandas:1.4.3'}" input: tuple val(meta), path(vcf) From f829c103d44870046e372e7cafed6fd6a6800b00 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 16 Dec 2024 00:07:28 -0800 Subject: [PATCH 159/161] update containers --- modules/local/gvftoindexandlog.nf | 2 +- modules/local/mergeIndices.nf | 2 +- modules/local/mergeLogfiles.nf | 2 +- 3 files changed, 3 insertions(+), 3 deletions(-) diff --git a/modules/local/gvftoindexandlog.nf b/modules/local/gvftoindexandlog.nf index 2ec147dc..bebaf06c 100644 --- a/modules/local/gvftoindexandlog.nf +++ b/modules/local/gvftoindexandlog.nf @@ -3,7 +3,7 @@ process GVF_TO_INDEX_LOG { conda "conda-forge::dask=2023.10.1" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'biocontainers/dask:2023.10.1-py11-ol9_cv1' - : 'quay.io/biocontainers/dask:2023.10.1-py11-ol9_cv1'}" + : 'daskdev/dask:2023.10.1-py3.11'}" input: tuple val(meta), path(gvf) diff --git a/modules/local/mergeIndices.nf b/modules/local/mergeIndices.nf index c2cddac0..75715469 100644 --- a/modules/local/mergeIndices.nf +++ b/modules/local/mergeIndices.nf @@ -5,7 +5,7 @@ process MERGE_INDICES { conda "conda-forge::dask=2023.10.1" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'biocontainers/dask:2023.10.1-py11-ol9_cv1' - : 'quay.io/biocontainers/dask:2023.10.1-py11-ol9_cv1'}" + : 'daskdev/dask:2023.10.1-py3.11'}" input: tuple val(meta), path(index) diff --git a/modules/local/mergeLogfiles.nf b/modules/local/mergeLogfiles.nf index 0dd27e31..a2b2101d 100644 --- a/modules/local/mergeLogfiles.nf +++ b/modules/local/mergeLogfiles.nf @@ -3,7 +3,7 @@ process MERGE_LOGFILES { conda "conda-forge::dask=2023.10.1" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ? 'biocontainers/dask:2023.10.1-py11-ol9_cv1' - : 'quay.io/biocontainers/dask:2023.10.1-py11-ol9_cv1'}" + : 'daskdev/dask:2023.10.1-py3.11'}" input: tuple val(meta), path(log_header) From 53eb35a8460f5f4ee82ad62169ec720b56cf999f Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 16 Dec 2024 00:15:32 -0800 Subject: [PATCH 160/161] update containers --- modules/local/mergeIndices.nf | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/modules/local/mergeIndices.nf b/modules/local/mergeIndices.nf index 75715469..f522d8a8 100644 --- a/modules/local/mergeIndices.nf +++ b/modules/local/mergeIndices.nf @@ -1,6 +1,6 @@ process MERGE_INDICES { tag "${meta.id}" - cpus 6 + cpus 4 conda "conda-forge::dask=2023.10.1" container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container From f6dcdf88b17477c522c2149f9ad81f073f660b28 Mon Sep 17 00:00:00 2001 From: Zohaib Anwar Date: Mon, 16 Dec 2024 00:33:27 -0800 Subject: [PATCH 161/161] updated for master --- .github/workflows/nextflow_CI.yml | 12 ++++++++++++ 1 file changed, 12 insertions(+) diff --git a/.github/workflows/nextflow_CI.yml b/.github/workflows/nextflow_CI.yml index d5ca39bb..f775bf1a 100644 --- a/.github/workflows/nextflow_CI.yml +++ b/.github/workflows/nextflow_CI.yml @@ -4,6 +4,9 @@ on: push: branches: - development + pull_request: + branches: + - master jobs: test_sarscov2_user: @@ -35,3 +38,12 @@ jobs: - name: Run pipeline test (reference) run: | nextflow run main.nf -profile docker --prefix "covidmvp-$(date +%Y-%m-%d)" --end_date $(date +%Y-%m-%d) -params-file covidmvp_clinical_params.yaml + + check_success: + name: Check if all tests passed + needs: [test_sarscov2_user, test_sarscov2_reference] + runs-on: ubuntu-latest + steps: + - name: Check job status + if: ${{ failure() }} + run: exit 1

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